Ethereal oxygen effects on structure and reactivity
by David Kent Johnson
A thesis submitted in partial fulfillment of the requirements for the degree Doctor of Philosophy in
Chemistry
Montana State University
© Copyright by David Kent Johnson (1988)
Abstract:
The role the oxygen atom plays in influencing the stereochemistry of electrophilic additions to
cis-8-oxabicyclo[4.3.0]non-3-ene, [1] and 8- oxatricylo[4.3.3.0]undec-3-ene, [7], was examined. A
complete absence of stereoselectivity was observed in [7], This was consistent with calculations
completed on the olefin that suggest: (1) there are two boat conformers existing for the alkene in
approximate equilibrium abundances, (2) the conformers have HOMOs of equal energy and as a. result
should have equal reactivity, and (3) there is no contribution by the oxygen atom in the HOMOs of
either conformer which could possibly have directed the addition. The modest stereoselectivity
observed in [1] was attributed to simple steric effects.
The role of the oxygen atom in imparting reactivity during solvolysis on the syn- and anti-tosylates
derived from [1] and [7] was examined. Identical reactivities and products were observed in the
solvolysis of the syn and anti-tosylates of [1]. This was interpreted to mean oxygen does not influence
reactivity in these compounds. A slight rate enhancement (1.53) was observed for the anti tosylate of
[7] relative to the syn-isomer. A stabilized hydrogen bonded intimate ion pair (IIP) was used to
rationalize this increased reactivity.
The role of the oxygen atom to influence the stereochemistry of catalytic hydrogenation in
3-methyl-8-oxabicylo[ 4.3.3.0]undec-3-ene, [ 35], was studied and modest stereoselectivity was
observed (3:1). This is suggestive of an oxygen/catalysts interaction (haptophilicty).
The olefins resulting from the palladium induced bond isomerization of [1] were characterized and
examined by the MM2 and MNDO methods. These olefins were found to exhibit increasing
thermodynamic stability as measured by heats of formation and hyperstability. This stability was used
to rationalize the bond isomerization on the basis of the Polanyi mechanism. A correlation between
hyperstability and HOMO n bond order was observed in this system.
The major ions in the EI mass spectrum of [1] were determined from an examination of the mass
spectra of a series of deuterium labelled analogues of [1] which were prepared. Fragmentation
mechanisms were proposed for the formation of these ions. ETHEREAL OXYGEN EFFECTS ON
STRUCTURE AND REACTIVITY
by
D avid K en t Jo h n so n
A th e s is su b m itte d in p a r tia l fu lfillm e n t
of th e re q u ire m e n ts f o r th e d e g re e
D octo r of P h ilo so p h y
in
C h e m istry
MONTANA STA TE UNIVERSITY
B ozem an, M ontana
May 1988
ii
APPROVAL
of a th e sis su b m itted b y
David K ent Johnson
T his th e sis h as b een re a d b y each member of th e th e sis committee
and h as been found to be s a tis fa c to ry re g a rd in g c o n te n t, E nglish u sa g e ,
form at, c ita tio n s , b ib lio g rap h ic s ty le , an d c o n siste n c y , an d is re a d y fo r
subm ission to th e College of G rad u ate S tu d ies.
Hcal 3 ', \9es
Date
C h a irp e rso n , G rad u ate Committee
A pproved fo r th e Major D epartm ent
_______
Date
H ead, Major D epartm ent
A pproved fo r th e College of G rad u ate S tu d ies
Date
Graduate Dean
m
STATEMENT OF PERMISSION TO USE
In p r e s e n tin g th is th e s is in p a r tia l fu lfillm en t of th e re q u ire m e n ts f o r
a d o c to ra l d e g re e a t M ontana S ta te U n iv e rs ity , I a g re e t h a t th e L ib r a r y
s h a ll m ake i t a v a ila b le to b o rro w e rs u n d e r r u le s of th e L ib r a r y .
I fu rth e r
a g re e t h a t c o p y in g o f th is th e s is is allow able o n ly f o r s c h o la rly p u r p o s e s ,
c o n s is te n t w ith " f a ir u s e "
a s p r e s c r ib e d in th e U .S .
C o p y rig h t Law .
R e q u e s ts f o r e x te n s iv e c o p y in g o r re p ro d u c tio n of th is th e s is sh o u ld b e
r e f e r r e d to U n iv e rs ity M icrofilm s In te r n a tio n a l, 300 N o rth Z eeb R o ad , A n n
A rb o r, M ichigan 48106, to whom I h a v e g r a n te d " th e e x c lu s iv e r ig h t to
re p ro d u c e a n d d is tr ib u te co p ies o f th e d is s e r ta tio n in a n d from m icrofilm
a n d th e r i g h t to r e p ro d u c e a n d d is tr ib u te b y . a b s tr a c t in a n y fo rm a t."
iv
To my mom an d dad fo r th e ir c o n sta n t love a n d . s u p p o r t.
’’T he re a l cycle y o u 're w o rk in g on
is a cycle called 'y o u r s e l f ."
"T he s tu d y of th e a r t of .m otorcycle m aintenance [o r ch em istry ] is
re a lly a m iniature s tu d y of the: a r t of ra tio n a lity its e lf.
W orking on a
m otorcycle [o r in c h e m is try ], w o rk in g Well, c a rin g , is to become p a r t of a
p ro c e s s , to achieve an in n e r p eace of m ind.
The m otorcycle [T he
ch em istry ] is p rim arily a m ental p h en om enon."
- R o b ert M. P irs ig
:
Zen an d th e A rt of M otorcycle M aintenance
V
ACKNOWLEDGEMENTS
T his e n d e a v o r could n o t h av e b e en com pleted w ith o u t th e help of a
num ber of p eo p le.
Special th a n k s a re e x te n d e d to Joe S e a rs , D ave T h e is te ,
an d Tim Schram f o r th e ir u n se lfish a s s is ta n c e , re s p e c tiv e ly , on th e m ass
sp ec tro m e te r,
th e
co m p u ter,
an d
th e
NMR; to
R ay L arso n
an d
D r.
F itzg e ra ld fo r th e ir a ss is ta n c e w ith x - r a y c ry s ta llo g ra p h y ; a n d to M ontana
In te rfa c e an d e sp ecially D r. Howald fo r th e ir a ss is ta n c e w ith o u r k in etic
ex p erim en ts.
d iscu ssio n s
Special th a n k s is also e x te n d e d to D r. C ra ig fo r h is h elp fu l
on
p h y sic a l-o rg a n ic
c h em istry
an d
fo r
th e
in te r e s t
an d
enthusiasm he h a s show n in my c a re e r; a n d to D r. M undy f o r h is in te g rity ,
h is s u p p o rt of s tu d e n ts , a n d fo r h is d eep devotion an d love of ch em istry
th a t he h a s o p en ly e x h ib ite d d u rin g my g ra d u a te y e a r s . L a stly my d e ep e st
a p p re cia tio n is e x te n d e d to my d e a r w ife, A n d re a, fo r h e r a ss is ta n c e w ith
w ord p ro c e s s in g an d h e r e v e r p re s e n t love an d com panionship.
V
vi
table o f contents
U S T OF TABLES...
U S T OF FIGURES..
ABSTRACT........
I. INTEOXTCTION,
Neighboring Group Participation by Oxygen.............
Oxygen Effects on Hydrogenation......................
Palladium Promoted Bond Isomerization in Cyclic Systems
Scope and Goals of this Investigation.................
2. RESUIHS AND DISCUSSION. .... ...... .
vii
.ix
xiv
• -1
. .1
.12
.17
.19
.21
Oxygen's Effect in Influencing Stereochemistry..
Oxygen's Effect in Influencing Reactivity......
A Search for an Oxygen/Catalyst Interaction....
An Examination of the Palladium Induced Bond
Isomerization of cis-8-oxabicylo[4.3.0]non-3-ene
An Examination of the Mass Spectrum of
. cis-8-oxabicyclo[4.3.0]non-3-ene...............
3. CONCLUSIONS.................
Summary of this Research
Suggested Future Work___
4. EXPERIMENTAL,
REFERENCES
82
129
vii
LIST OF TABLES
Table
Page
1.
Splvolytic rate influences by oxygen and sulfur................... 2
2.
Relative rates of solvolysis of
p-bromobenzenesulfonates in acetic acid at 50°C.................... 3
3.
Acetolysis of arenesulfonates.......................................6
4.
Oxygen's inductive effect on carbon-carbon bond
participation...................................................... 7
5.
Oxymercuration competition results................................. 8
6.
Relative rates of catalytic hydrogenation..... ................... 12
7.
Relative substrate/catalyst affinities............................ 13
8.
Product studies on cis-8-oxabicyclo[4.3.0]non-3-ene...............22
9.
Product studies on 8-oxatricyclo[4.3.3.O ]
undec-3-ene...............................
22
Ground state conformational energies for
Si-Oxabicyclo[4.3.0] non-3-ene, [1].........................
29
10.
11.
Ground state conformational energies for
8-oxatricyclo[4.3.3.0]non-3-ene, [ 7 ] .............................. 30
12.
HOMO conformational energies of cis-8-oxabicyclo[4.3.0]
non-3-ene......................................................... 32
13.
HOMO conformational energies of
8-oxatricyclo [4.3.3.0 ]undec-3 -ene................................. 32
14.
Kinetic results of the 50% aqueous methanolysis of
[19] and [31]...................... ................ '............. 43
\
15.
Kinetic results of the 50% aqueous methanolysis of
[24] and [32]..................
44
16.
Activation parameters of the 50% aqueous methanolysis
of [19], [31], [24] and [32]....... ■.............................. 44
17.
Modelled bicyclic tosylate energies............................... 48
18.
Calculated olefinic energies (Kcal/mole).......................... 50
viii
U S T OF TABLES - Continued
19.
Modelled tricyclic tosylate stabilities (Kcal/mole).............. 53
20.
Calculated carbocation stabilities (Kcal/mole)................... 54
21.
MM2 calculated energies (Kcal/mole)............................... 64
22.
MNDO calculated heats of formation (Kcal/mole)....................66
23.
HCMO Pz atomic orbital coefficients of olefinic
carbons and HOMO tt bond orders................................... 66
24.
Atomic coordinates (xlO4) and isotropic thermal
parameters (A°xl03) of [19]...................................... 112
25.
Bond lengths (A°) of [19].......................
113
26.
Bond angles (°) of [19].............
114
27.
Atomic coordinates (xlO4) and isotropic thermal
parameters (A0XlO3) for [24]..................................... 118
28.
Bond lengths (A”) for [24]..........................
29.
Bond angles (°) of [24].......................................... 120
..119
KEST OF FIGURES
Figure
Page
1.
Heteroatcm stabilization in a norobomyl system.. ........... ■..... 3
2.
Oxygen intermediate stabilization........
3.
Oxygen participation in endo-9-oxabicyclo[4.2.1]2-yl-p-brcmobenzenesulfonate....................................... 4
4.
Oxygen participation in 2-ethoxybenzl-3cyclohexyl-p-nitrobenzoate.......................................... 5
5.
Transannular dipole effect......................................... 6
6.
Predicted conformation of cis-8-oxabicyclo
[4.3.0] n o n - 3 - e n e . .... .......
4
9
7.
Oxymercuration of cis-8-oxabicyclo [4.3.0] non-3-ene.................9
8.
Proposed oxygen participation in the oxymercuration
of cis-8-oxabicyclo [4.3.0]non-3-ene...........................
10
9.
Steric bias in cis-8-oxabicyclo[4.3.0]non-3-ene...................10
10.
Absence of oxygen participation in 8-oxatricyclo
[4.3.0] undec-3-ene................
11
Conplexation if cis-8-oxabicvclo[4.3.0]non-3-ene. .
[1], to platinum.......................................
14
Effect of tetrahydrofuran on the reduction of
cyclohexene.........
14
11.
12.
13.
Effect of cis-8-oxabicyclo[4.3.0]nonane on the
reduction of cyclohexe............................................ 15
14.
Haptophilicity involving the methoxy group........................16
15.
Haptophilicity involving the ester group.......................... 16
16.
Stereospecific hydrogenation of 2-methylenecis-1,5 dicarboxymethyl[4.3.0]octane.............................. 17
17.
Palladium promoted bond isomerization in the
methylcyclohexene system.... ......................................18
18.
Palladium induced bond isomerization of
cis-8 -oxabicyclo [4.3.0] non-3-ene.................................. 18
X
U S T OF FIGURES - continued
19.
Synthesis of cis-8-oxabicyclo[4.3.0]non-3-ene,
[1], and 8-oxatricyclo[4.3.3.0]undec-3-ene, [7]...................21
20.
Determination of the stereochemistry of the svnalcohol of [1].................................................... 23
21.
% enhancement of NOE experiment, on svn-methoxv
derivative of [1]................
25
22.
Determination of the stereochemistry of the svnalcohol of [7].................................................... 26
23.
Equilibrium conformations of
8-oxabicyclo [4.3.0] non-3-ene...................................... 30
24.
Equilibrium conformations of
8-oxatricyclo [4.3.3.0]undec-3-ene................................. 31
25.
HCMD contour plots of 8-cis-bicyclo[4.3.0]
non-3-ene..... ...........................
34
26.
HCMO contour polots of 8-oxatricyclo[4.3.3.0]
undec-3-ene....................................................... 34
27.
Does the oxygen atom influence reactivity in
the solvolysis of these tosylates?................................ 38
28.
Boat conformations of anti-isomers. [A] and [C]...................38
29.
Boat conformations of svn-isomers. [B] and [D]................. ,.38
30.
Syntheses of svn-and anti-tosvlates dervived from[I].;............ 40
31.
Syntheses of svn- and anti-tosvlates derived from[7].............. 41
32.
ORTEP drawings of the x-ray structures of [19] and [24]............42
33.
Product studies of 50% aqueous methanolysis of [19]............... 45
34.
Product studies of 50% aqueous methanolysis of [31]............... 46
35.
Product studies of 50% aqueous methanolysis of [24]............... 46
36.
Product studies of 50% aqueous methanolysis of [32]............... 47
37.
Reaction scheme for the solvolysis of [19], [24],
and [31]...........................................................49
38.
Proposed reaction scheme for the solvolysis of [32]............... 54
xi
LTST1OF FIGURES - continued
39. Proposed oxygen/catalyst interaction.............................. 57
4CL
Synthesis of 3-methyl-8-oxatricyclo[4.3.3.0]
dodec-3-ene, [35]................................................. 58
41.
GC traces of the palladium induced bond
isomerization of cis-8-oxabicyclo [4.3.0] non-3-ene........ .59
42.
Bond migrations and olefinic reductions of
cis-8-oxabicyclo [4.3.0] non-3-ene.........
60
43.
Preparation of cis-8-oxabicyclo[4.3.0] non-2-ene...................61
44.
Synthesis of -1,6-8-oxabicyclo[4.3.0]nonene....................... 61
45.
Reaction composition of the hydrogenation (Pd/C)
of cis-bicyclo[4.3.01non-3-ene at 3 minutes (a)
and 15 minutes (b)............. .'............................ .
62
46.
Polanyi1s hydrogenation mechanism..................
63
47.
Hyperstable olefins............................................... 65
48.
HCMO contour plots of [1], [13], [14], and [15].................. 67
49.
70 eV EI mass spectrum of cis-8-oxabicyclo
[4.3.0] non-3-ene, [1]........................
69
70 eV EI mass spectrum of cis-8-oxatricyclo
[4.3.3.0] undec-3-ene, [7]. .......................
70
50.
51.
Deuterium labeled analogues of cis-S-oxabicyclo
[4.3.0]
non-3-ene, [1]......................................... 71
52.
Synthesis of cis-7,7,9,9-tetradeutero-8oxabicyclo[4.3.0]non-3-ene, [42]............
53.
Syntheses of cis-2,2,5,5-tetradeutero-8-oxabicyclo[4.3.0] non-3-ene, [43] and cis-2,2,5,5,7,7,9,9ocatadeutero-8-oxabicyclo[4.3.0] non-3-ene, [44].....
71
72
/
54.
70 eV EI mass spectrum of cis-7,7,9,9-tetradeutero8-oxabicyclo[4.3.0]non-3-ene, [42]...................... '........ 73
55.
70 eV EI mass spectrum of cis-2,2,5,5-tetradeutero8-oxabicyclo[4.3.0]non-3-ene, [43]....... .•....................... 73
56.
70 eV EI mass spectrum of cis-2,2,5,5,7,7,9,9octadeutero-8-oxabicyclo[4.3.0]non-3-ene, [44]................... .74
xii
U S T OF FIGURES - continued
57.
Loss of H0CH2 from cis-8-oxabicyclo[4.3.0]
non-3-ene, [1].....................................................
58.
loss of CH3-CH=CH-CH2 from cis-8-oxabicyclo
[4.3.0] non-3-ene, [1]........................................... .
59.
Loss of CH3-0-CH2 from cis-8-oxabicyclo
[4.3.0] non-3-ene, [1]........................................... .
60.
Plot of Intq30 - Cx ) vs tine (seconds) for the 50%
aqueous methanolysis of [19] at 35.84 °C......................... 84
61.
Plot of Intq30 - Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [19] at 50.00 °C......................... 85
62.
Plot of Into* - cx) vs time (seconds) for the 50%
aqueous methanolysis of [19] at 62.87 °C......................... 86
63.
Plot of Intq30 “ Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [31] at 35.78 °C......................... 87
64.
Plot of Intq30 ~ Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [31] at 50.20 °C........................ 88
65.
Plot of Intq30 - Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [31] at 63.00 °C......................... 89
66.
Plot of Intq30 " Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [24] at 35.82 0C ......................... 90
67.
Plot of Intq30 ~ Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [24] at 50.10 0C ...................... ...91
68.
Plot of Intq30 ~ Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [24] at 63.00 °C................. ........92
69.
Plot of Intq30 - Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [32] at 35.70° C ... ...................... 93
70.
Plot of Intq30 ~ Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [32] at 50.15° C ......................... 94
71.
Plot of Intq30 ~ Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [32] at 62.90° C ......................... 95
72.
Plot of In(k)
vs
1/T (K°-1) for [19]................................ 96
73.
Plot of In(k)
vs
1/T (K0-1) for [31]...............................97
74.
Plot of In(k)
vs
1/T (K°-1) for [24]...............
98
xiii
LIST OF FIGURES - continued
75.
Plot of In(K) vs 1/T (K0-1) for [32]............................. .
•76.
ORTEP drawing of [19]........................ ................... ^12
77.
ORTEP drawing of [24]
117
x iv.
ABSTRACT
T he role th e oxygen atom p la y s in in flu en c in g th e ste re o c h e m istry of
electro p h ilic a d d itio n s to c is- 8 - o xabicy clo [4 .3 .0 ] non - 3 -e n e , [1] and 8o x a tric y lo [4 .3 .3 .0 ]u n d e c -3 -e n e , [7 ], was exam ined. A com plete ab sen ce of
s te re o s e le c tiv ity was o b se rv e d in [7 ] ,
T his was c o n siste n t w ith
calculations com pleted on th e olefin th a t s u g g e s t: ( I ) th e r e a re two b o at
conform ers e x is tin g fo r th e alkene in approxim ate equilibrium a b u n d a n c e s,
(2) th e conform ers h av e HOMOs of eq u al e n e rg y an d as a. re s u lt should
h a v e eq u al re a c tiv ity , a n d (3) th e re is no c o n trib u tio n b y th e o xygen atom
in th e HOMOs of e ith e r conform er w hich could p o s sib ly h av e d ire c te d th e
a d d itio n . T he m odest ste re o s e le c tiv ity o b se rv e d in [1] was a ttrib u te d to
simple s te ric e ffe c ts.
The role of th e oxygen atom in im p a rtin g re a c tiv ity d u rin g solvolysis
on th e s y n - a n d a n ti- to sy la te s d e riv e d from [1] a n d [7] was exam ined.
Id en tical re a c tiv itie s an d p ro d u c ts w ere o b se rv e d in th e solvolysis of th e
s y n an d a n ti- to sy la te s of [ I ] . T his was in te rp re te d to mean o xygen does
n o t in flu en ce re a c tiv ity in th e se com pounds. A s lig h t r a te enhancem ent
(1 .5 3 ) was o b s e rv e d fo r th e a n ti to sy la te of [7] re la tiv e to th e s y n -isom er.
A stab ilized h y d ro g e n b o n d ed intim ate ion p a ir (IIP ) was u s e d to ratio n alize
th is in c re a se d re a c tiv ity .
T he role of th e o x y g en atom to in flu en ce th e ste re o c h e m istry of
c ataly tic h y d ro g e n a tio n in 3-m eth y l-8 -o x ab icy lo [ 4 .3 .3 .0 ]u n d e c -3 -e n e , [ 35],
was s tu d ie d and m odest s te re o s e le c tiv ity was o b se rv e d (3 : I ) . T his is
su g g e s tiv e of a n o x y g e n /c a ta ly s ts in te ra c tio n (h a p to p h ilic ty ).
T he olefins r e s u ltin g from th e palladium in d u c ed b o n d isom erization of
[1] w ere c h a ra c te riz e d an d exam ined b y th e MM2 a n d MNDO m ethods.
T hese olefins w ere fo u n d to ex h ib it in c re a s in g therm odynam ic sta b ility as
m easured b y h e a ts of form ation an d h y p e rs ta b ility . T h is s ta b ility was u se d
to ratio n alize th e b o n d isom erization on th e b a sis of th e Polanyi
m echanism . A co rre la tio n betw een h y p e rs ta b ility an d HOMO n b o n d o rd e r
was o b se rv e d in th is s y s te m .
T he major ions in th e BI mass sp ec tru m of [1] w ere d eterm in ed from a n
exam ination of th e m ass s p e c tra of a s e rie s of d eu teriu m lab elled analogues
of [1] w hich w ere p re p a re d . F rag m en tatio n mechanisms w ere p ro p o sed fo r
the form ation of th e se io n s.
I
CHAPTER I
INTRODUCTION
N e ig h b o rin g G roup P a rtic ip a tio n b y O xygen
O xygen co n tain in g h e tero cy c le s a re u b iq u ito u s to o rg a n ic ch em istry
a n d , th e re fo re , th e e ffe c ts th a t a n o x y g en atom im p arts on re a c tiv ity an d
s tr u c tu r e of th e molecule a re of g re a t im portance to th e o rg a n ic chem ist.
C lassically, th is re a c tiv ity h a s b e en w idely stu d ie d th ro u g h th e u se of
a b so lu te an d re la tiv e k in e tic s , p ro v id in g in s ig h ts in to re a c tio n mechanisms
an d e lu c id a tin g o x y g e n 's role in th e chemical tra n s fo rm a tio n .1 ’2 ’3 -4 ’5
S u rp ris in g ly , th e s e s tu d ie s h av e o ften show n co n flictin g in flu en c es im p arted
b y oxygen!
In some cases th e ox y g en atom h as b een show n to en h an ce
re a ctio n r a t e s ; w hile in o th e r com pounds, o x y g en h a s b e en show n to r e ta r d
re a ctio n r a te s .
I n te r p r e tin g o x y g e n 's e ffe c t in im p a rtin g re a c tiv ity on th e
molecule h a s also b e en d ifficu lt b e ca u se o x y g en does n o t e a sily s h a re its
lone p a ir e le c tro n s in th e stab ilizatio n of p o sitiv e c h a rg e s , a con seq u en ce of
its h ig h e le c tro n e g a tiv ity .
As a r e s u lt, th e v a rio u s e ffe c ts o x y g en im p arts
on s tr u c tu r e a n d re a c tiv ity a re n o t com pletely u n d e rs to o d .
In solvolytic re a c tio n s oxygen h a s b e e n show n to stab ilize p o sitiv e
c h a rg e s
w ith
its
lone
p a rtic ip a tio n 5 (N G P ).
p a ir
e le c tro n s
th ro u g h
n e ig h b o rin g
g ro u p
T his stab ilizatio n ty p ic a lly r e s u lts in an en h an ced
ra te (anchim eric a s s is ta n c e ).
O x y g en 's in flu e n c e , h o w ev er, h a s b e en shown
to b e more s u b tle th a n th a t of n itro g e n o r s u lfu r, d u e to th e ir low er
2
e le c tro n e g a tiv itie s a n d more d iffu se lone p a ir o rb ita l.
T his makes n itro g e n
an d s u lfu r b e tte r able to stab ilize p o sitiv e c h a r g e s .6 ' 7 *8 G ratz an d Wilder3
have com pared su c h heteroatom in flu en c es fo r o x y g en a n d s u lfu r ( Table I ).
Note th e la rg e 752 r a te enhancem ent of th e exo-tric y c lic su lfid e re la tiv e to
th e carb o n analog com pared to th e s u b tle 2.53 r a te enhancem ent of th e
e x o -tric y c lic e th e r re la tiv e
to th e
c arb o n an alo g .
T he a u th o rs have
a ttrib u te d th e la rg e r a te enhancem ents to lone p a ir NGP b y th e heteroatom ,
a n d a stab ilized in te rm e d ia te w ith delocalized p o sitiv e c h a rg e is p ro p o sed
(F ig u re I ) .
A lbeit s u b tle , o x y g e n 's e ffe c t can b e c o n sid e re d sig n ific a n t as
S c h le y erxo s u g g e s ts ,
"th e
d etectio n
of a n y r a te
en h an cem en t due to
anchim eric a s s is ta n c e , no m a tte r how sm all, is in d ic a tiv e of s tro n g (n o t
w eak!) p a rtic ip a tio n b y th e n e ig h b o rin g g ro u p " .
T able I . Solvolytic r a te in flu en ces b y o x y g en a n d s u lfu r.
Z
PNBO ^^
S
0 . BO
CH2
0. 70
S
PNBO ^^
R e la t iv e R a te
752
O
2. 53
CH2
I. 00
3
+ 'Z
-OPNB
F ig u re I . H eteroatom stab ilizatio n in a n o rb o rn y l s y ste m .
Closson
et
a l . T1
also
te tra h y d ro fu ra n y l g ro u p .
has
fo u n d
anchim eric
a ss is ta n c e
by
th e
T his r a te enhancem ent was show n to b e g re a te r
th a n th a t fo r th e m ethoxyl g ro u p , w hich in tu r n was f a r g r e a te r th a n th e
c o rre sp o n d in g s tr a ig h t chain alkane (T ab le 2 ).
U nlike th e conform ationally
rig id n o rb o rn y l sy stem s of W ilder, in th e se sy stem s g re a t conform ational
fle x ib ility e x is ts .
As a r e s u lt, o x y g en is b e tte r able to stab ilize p o sitiv e
c h a rg e th ro u g h NGP (F ig u re 2 ).
Table 2. R elative ra te s of solvplysis of p -b ro m o b en zen esu lfo n ates in
a cetic acid a t 50 C.
Compound
Me-(CH2)4-CH2-O B s
MeO-(CH2)4-C H 2-O B s
R ela tiv e R a te
1. OO
657
O-
(CH2)n-O B s
n = I
13. 1
n = 2
26. 3
n = 3
1510
n = 4
12400
n = 5
1380
4
F ig u re 2. O xygen in term ed iate stab iliza tio n .
P a q u e tte e t a l12 o b se rv e d a 24 fold ra te enhancem ent in th e ra te of
s o lv o ly s is
of
e n d o -9 -o x a b ic y c lo [ 4 .2 .1 ] -2 -y l-p -b ro m o b en z en su lfo n a te s
com pared to its ex o -isom er.
oxonium
ion
upon
T he e n d o -isom er was fo u n d to p ro d u c e th e
a c e to ly s is ,
while
th e
exo-isom er
re a c te d
by
th e
carbocation in term ed iate w hich re a rra n g e s to th e oxonium ion (F ig u re 3 ).
OBs
OBs
F ig u re 3. O xygen p a rtic ip a tio n in en d o -9 -o x ab ic y c lo f4 .2 .1 1 -2 -y l-p b ro m o b en zen esu lfo n ate.
5
Sunko1 *
re c e n tly
has
illu s tra te d
o xygen
p a rtic ip a tio n
in
2-
( e th o x y b en z y l) - 3 -m e th y l- 2 - cyclo h ex y l-p -n itro b e n z o a te . A lth o u g h h e o b se rv e d
a s u b tle 1.14 r a te in c re a s e o v e r th e c o rre sp o n d in g c arb o n analog,, a
sig n ific a n tly re d u c e d
(1.164) se c o n d a ry a -d e u te riu m iso to p e e ffe ct was
o b s e rv e d , a s tr o n g in d icatio n of o x y g en p a rtic ip a tio n in th e ionization of
th e e s te r (F ig u re 4 ).
F ig u re 4. O xygen p a rtic ip a tio n in 2 - e th o x y b e n z y l- 3 - cy clo h ex y l-p n itro b e n z o a te .
C o n v ersely , T a rb e ll a n d H azen14 o b se rv e d a r a te r e ta r d in g e ffe ct b y
o x y g en .
T h e y in v e stig a te d th e role o x y g en p la y ed in th e solvolysis of
simple o x y g en h e tero cy c le s (T ab le 3.) a n d fo u n d th e r a te s of solvolysis
w ere a n o rd e r of m agnitude slow er th a n would b e e x p e c te d from an
in d u c tiv e e ffe c t b y o x y g e n .
T his inform ation led them to b eliev e th a t th e y
w ere dealin g w ith a tra n s a n n u la r dipole e ffe c t (F ig u re 5 ).
T he dipole
asso ciated w ith e th e r o x y g en was d e sta b iliz in g th e in c ip ie n t carbonium ion
in th e so lv o ly sis, th u s r e ta r d in g th e r a te .
6
T able 3. A cetolysis of a re n e s u lfo n a te s .
OBs
I
OBs
6 Cr"* C
I. 4
Cf
—
13. 6
0. 55
2. 4 7
____/ O B s
6
__ / O B s
r a te x IO5 s e c .
OBs
F ig u re 5. T ra n s a n n u la r dipole e ffe c t.
U sing
th e
m ethod
of
" in c re a sin g
e lec tro n
d em an d ",
G assm an15
exam ined th ro u g h b o n d NGP of th e c a rb o n -c a rb o n b o n d of an ep o x id e,
cyclopropyl g ro u p ,
an d a n -sy ste m
(T ab le 4 ).
B y exam ining th e a -
m ethyl/ h y d ro g e n ra tio , th e c h an g in g e lectro n ic e ffe cts could b e isolated
from th e c h an g in g s te r ic e ffe cts of th e molecule.
T his m ethod is b ased on
th e assum ption th a t if th e e lec tro n dem and of th e in c ip ie n t cabonium ion in
th e tra n s itio n s ta te is sa tisfie d b y th e electro n d e n s ity d o n ated b y a
s u b s titu e n t on th e carb o n atom , th e n a rem ote fu n c tio n g ro u p will not
p a rtic ip a te in th e re a c tio n . T he re la tiv e a b ility of a fu n c tio n a l g ro u p to be
involved in NGP was determ ined b y com paring th e ra te w hen th e electro n
demand was sa tisfie d b y s u b s titu e n ts ( te r tia r y c a rb o c a tio n s) to th e ra tio
w hen e lec tro n dem and was satisfied b y a rem ote fu n ctio n al g ro u p ( sec o n d a ry
c a rb o c a tio n s ).
7
Table 4.
O x y g e n 's in d u c tiv e e ffe ct on c a rb o n -c a rb o n b o n d p a rtic ip a tio n .
Com pound
TsO
R
TsO
R
R ela tiv e R atio (M e/H )
IO11
TsO
R
IO14
TsO
R
I
G reat anchim eric a ss is ta n c e was o b s e rv e d fo r all fu n c tio n a l g ro u p s .
N ote, h o w ev er, th e sig n ific a n tly re d u c e d r a te enhancem ent of th e epoxide
re la tiv e to its cyclo p ro p y l g ro u p an alo g .
T his is a ttr ib u te d to o x y g e n 's
in d u c tiv e e ffe ct on c a rb o n -c a rb o n b o n d p a rtic ip a tio n .
T he M uhdy g ro u p also m aintains a n a g g re ss iv e p ro g ram d ire c te d tow ard
th e s tu d y of th e role o x y g en p lay s in im p a rtin g s tr u c tu r e a n d re a c tiv ity on
th e
m olecule.
O tz e n b e rg e rx6
(1971)
in itia te d
com pleting a com petitive o xym ereu ratio n s tu d y .
th is
in v e stig a tio n
by
A p a r t of th is s tu d y is
re p re s e n te d in Table 5.
\
8
Table 5 . Oxymerc u ra tio n com petition r e s u l t s .
R ela tiv e R a te + 10%
Com pound
O
'
CC- ■
Cd 2
CD0 3
I. 0 0
0 . 81
0 . 11
0 . 40
cx> *
0 . 15
From th is s tu d y he concluded th a t a n y s u b stitu tio n on th e rin g re ta r d s
th e
r a te .
More
in te re s tin g ly ,
O tz e n b e rg e r
n o ted
th a t
c is - 8-
o x a b ic y c lo [4 .3 .0 ]n o n -3 -e n e , [1 ], was n e a rly e ig h t times a s re a c tiv e as c isb ic y clo [4 .3 .0 ]n o n -3 -e n e , [2 ].
A sim ilar, th o u g h sm aller, ra te enhancem ent
was o b se rv e d fo r tr a n s -8 -o x a b ic y c lo [4 .3 .0 ]n o n -3 -e n e , [3 ]. T h is d ata seemed
to s u g g e s t a ra te e n h an c in g e ffect im p arted b y o x y g en .
In
c o n sid e rin g
th e
p re fe rre d
conform ation
of
[1 ] ,
O tz e n b e rg e r
reaso n ed th a t th e re p u lsio n betw een th e o xygen n o n -b o n d in g e lec tro n s an d
th e n -e le c tro n s of th e double bond would fa v o r conform ation [1A] as shown
in F ig u re 6.
He u se d an "1HNMR a rg u m e n t an d th e w ork of Cope"17 and
Casadevall"18 (who concluded th a t
[2]
an d
c is -b ic y clo [4 .2 .0 1 o c t-3 -e n e ,
re s p e c tiv e ly , e x ist in p se u d o -b o a t conform ations) to s u p p o rt th is conclusion.
9
In th is conform ation, O tz e n b e rg e r co n sid e re d s u b s titu tio n on th e rin g to be
su ffic ie n tly rem ote to re s u lt in th e n -fa c e s of th e double bond to be
s te ric a lly e q u iv a le n t.
IA
F ig u re 6.
P re d ic te d conform ation of cis_-8-oxabicyclo[4 .3 .0 ]n o n -3 -e n e .
O tz e n b e rg e r also found th a t o x y m ercu ratio n of [1] gav e p red o m in an tly
th e sy n alcohol [5] (F ig u re 7 ), in a ra tio of 3 to I o v e r th e a n ti alcohol
[6 ].
I
3
F ig u re 7. O xym ercuration of c is -8 -o x ab icy clo [4 .3 .0 ]n o n -3 -e n e .
To
rationalize
th e se
fin d in g s,
and
by
analogy
to
th e
oxygen
p a rtic ip a tio n fo u n d b y Wilder in a analogous n o rb o rn y l sy stem (F ig u re I ) ,
O tz e n b e rg e r p ro p o se d th e following m echanism (F ig u re 8) in v o lv in g oxygen
n e ig h b o rin g g ro u p p a rtic ip a tio n .
In th is m echanism, [1] b ecau se of its
lim ited conform ational flex ib ility a d o p ts a conform ation in w hich oxygen
do n ates e lec tro n
d e n s ity from its lone p a ir e lec tro n s
to stab ilize th e
10
m ercurinium in te rm e d ia te.
This stab ilized in term ed iate was u sed to account
fo r th e in c re a se d re a c tiv ity of [ I ] .
&+
AcOHg
A)
%
8V^p0
HOH
Iron s a tta c k
m ajor
F ig u re 8. P roposed oxygen p a rtic ip a tio n .
W ilkening19 (1984), unlike O tz e n b e rg e r, did not c o n sid e r th e n -fac es of
[1A] to be s te ric a lly e q u iv a le n t. As illu s tra te d in F ig u re 9, th e n -sy ste m of
the cyclohexene r in g a c tu a lly a p p e a rs to b e facially d issim ilar.
One face of
th e double bond is sy n to th e oxapropano g ro u p while th e o th e r face of th e
double bond e x p e rie n c e s only two h y d ro g e n atoms in c o n tra d istin c tio n .
syn
anti
F igure 9. S te ric b ias in cis - 8 -oxabicyclo [4 .3 .0 1 non - 3 - e n e .
To
a d d re s s
O tz e n b e rg e r's
th is
fa c to r
mechanism
of
s te r ic
inv o lv in g
nonequivalence
o x y g en
and
p a rtic ip a tio n ,
to
te s t
W ilkening
s y n th e siz e d 8 -o x a tric y c lo [4 .3 .3 .0 ]u n d e c -3 -e n e , [7 ]. In a s e n s e , he co n sid ered
[7] to be a com bination of [1] an d [2 ].
W ilkening also c o n sid e re d th e n -
11
system of [7] to be facially sim ilar, elim inating th e s te r ic nonequivalence
th a t he believed e x iste d in [ I ] .
As a re s u lt, W ilkening believed a n y
ste re o se le c tiv e a d d itio n s to [7] could b e more a c c u ra te ly a ttrib u te d to
oxygen p a rtic ip a tio n .
7
When W ilkening su b jec te d [7] to an epoxidation s tu d y u s in g mCPBA
an d to an oxy m ercu ratio n s tu d y cataly zed b y tra c e am ounts of n itric acid in
m ethanol,
he found
no indicatio n
of o x y g en p a rtic ip a tio n
in flu en cin g
p ro d u c t s te re o c h e m is try ;20 th e p ro d u c t ra tio s in b o th s tu d ie s w ere I to I
(F ig u re 10).
oxygen
As a r e s u lt, he concluded th a t simple s te ric e ffe c ts, not
p a rtic ip a tio n ,
w ere
d is trib u tio n s in [1] an d in [7 ].
re sp o n sib le
fo r
th e
o b se rv e d
p ro d u c t
From th is s tu d y , h o w ev er, Wilke n in g was
unable to explain th e in c re a se d re a c tiv ity of [1] o v e r [2 ],
9
MCPBA
1 :1
10
F ig u re 10. A bsence of oxygen p a rtic ip a tio n in 8ox atricy clo [4 .3 .3 .0 ]u n d e c -3 - e n e .
11
12
O xygen E ffects on H yd ro g en atio n
The c ata ly tic h y d ro g e n a tio n of olefins h a s b een s tu d ie d b y a num ber
of in v e stig a to rs u s in g a v a rie ty of re a c tio n te c h n iq u e s.
In th e se s tu d ie s
re a ctio n so lv e n t, h y d ro g e n p r e s s u r e , s u b s tr a te c o n c e n tra tio n , c a ta ly s t m etal,
th e metal to s u p p o rt ra tio , th e p re tre a tm e n t of c a ta ly s t, a n d even th e
seq u en ce in w hich th e olefin an d h y d ro g e n a re ad d ed to th e c a ta ly st all
have been fo u n d to h a v e an e ffe ct on th e re a ctio n r a t e . 21*22
T heodore23 (1978) in v e stig a te d th e ro le o xygen im p arts on re a c tiv ity in
an non-ionic situ a tio n b y com paring th e h y d ro g e n a tio n ra te s of [1 ] , [2 ], a n d
cyclohexene (T able 6 ).
In th e com petitive s tu d y , c a rrie d o u t b y m ixing [1]
o r [2] w ith cyclohexene in th e same re a c tio n v e ss e l, [1] was fo u n d to b e
more re a c tiv e th a n [2] o r cy clo h ex en e, a g ain su g g e s tiv e of a n o x y g en r a te
e n h an c in g e f f e c t!
In th e non-com petitive s tu d y , c a rrie d o u t in se p a ra te
re a ctio n v e sse ls fo r th e same p e rio d of tim e, [1] was fo u n d to b e 6 times
as re a c tiv e as [2 ] , sim ilarly a ttr ib u te d to a n o x y g en r a te e n h a n c in g e ffe c t.
T able 6.
R elative ra te s of c ataly tic h y d ro g e n a tio n .
Olefin
Com petitive
cyclohexene
1.00
I
2
6.59
4.92
N on-com petitive
1.00
0.78
0.13
13
T heodore also com pleted a n u m b er of com petitive a n d non-com petitive
h etero ato m / c a ta ly s t a ffin ity s tu d ie s (T ab le 7 ).
T h ese re s u lts re p re s e n t th e
ra tio s of com plexed to fre e s u b s tr a te re la tiv e to th e ra tio of complexed to
fre e c y clo h ex en e. T he re s u lts of th e com petitive s tu d y r e p r e s e n t a g re a te r
a ffin ity of [1] to b in d to th e c a ta ly s t o v e r [2] o r cy clo h ex en e.
The re s u lts
of, th e xnon-com petitive s tu d y w ere also u s e d to a rg u e fo r a p o sitiv e
o x y g e n /c a ta ly s t a ffin ity .
B ecause th e ra tio of c a ta ly s t to s u b s tr a te was
approxim ately eq u al to one, T heodore en v isio n ed one molecule of [1] h a v in g
th e a b ility to complex to more th a n one c a ta ly s t site as show n in F ig u re
11.
T his com plexation would p ro h ib ite d s u b s e q u e n t molecules to complex to
th e c a ta ly s t, th u s re d u c in g th e ra tio fo r [1] in th e n o n -co m p etitiv e s tu d y .
T heodore b eliev ed th is oxygen / c a ta ly s t in te ra c tio n p ro v id e a n en tro p ic
ra tio n a l to a cc o u n t fo r th e in c re a se d re a c tiv ity of [1] o v e r [2 ].
Table 7.
R elative s u b s tr a te /c a ta ly s t a ffin itie s.
Olefin
cyclohexene
I
2
Com petitive
1.00
3.36
0.88
N oncom petitive
1.00
0.75
0.13
14
F igure 11. Com plexation of cis,-8-o x ab icy clo [4 .3 .0 ] n o n -3- e n e , to
platinum .
G lancy 4 (1983) also o b serv ed a o x y g e n /c a ta ly s t in te ra c tio n .
He
stu d ie d th e e ffe c t of oxygen h etero cy cles on th e cata ly tic h y d ro g e n a tio n of
cyclohexene an d fo u n d th a t bo th te tra h y d ro fu ra n (F ig u re 12) and c is-8 oxabicyclo[ 4 .3 .0 ] n o n a n e , [1 2 ], (F ig u re 1 3 ), re ta rd e d th e r a te of red u c tio n of
cyclohexene.
He ratio n alized th e se re s u lts b y re a so n in g th a t th e e th e re a l
oxygen in te tra h y d ro fu r a n an d [12] a b so rb e d on to c a ta ly s t s ite s norm ally
u sed fo r h y d ro g e n a b so rp tio n .
T his p re v e n te d cyclohexene from re a ch in g
th e c a ta ly s t s u rfa c e th u s d e c re a sin g its r a te of re d u c tio n .
CE -7.22
-2.32
with Q
-1.16
LN ([CYC LOH E X E N E D
F igure 12.
Effect of te tra h y d ro fu ra n on th e re d u c tio n of cyclohexene.
15
2.02 M1
in EtOH
■209M
Lu 30- ■
no inhibitor.
TlMEI MIN.)
F ig u re 13.
Effect of cis - 8 - oxabicyclo [4 .3 .0 1 nonane on th e re d u c tio n of
cy clo h e x e n e .
As a g e n eraliz a tio n , th e ste re o c h e m istry of c ataly tic h y d ro g e n a tio n s of
olefins re s u lts in th e cis additio n of two h y d ro g e n atom s from th e less
s te ric a lly h in d e re d side of th e double b o n d .
oxygen
coordination
d ire c tin g
cata ly tic
H ow ever, s e v e ra l acco u n ts of
h y d ro g e n a tio n
have
re c e n tly
b een r e p o r te d . T his a n c h o rin g e ffe ct ( h a p to p h ilic ty ) 25 •26 h a s b een o b se rv e d
b y a num ber of in v e s tig a to rs .
Thom pson e t a l2-7 o b se rv e d th e d ire c tiv e effect of th e m ethoxy g ro u p
in th e cata ly tic h y d ro g e n a tio n o v e r P d / C an d P t / C of 7-m e th o x y -IOah y d ro x y m e th y l-1 ,2 ,3 ,9 ,1 0 ,lO a -h e x a h y d ro p h e n a th re n e (F ig u re 14).
T h ey
found th e cis_ re d u c tio n p ro d u c t was h ig h ly fav o red in so lv en ts h a v in g h ig h
d ie le ctric c o n sta n ts (DMF, EtOH, an d T H F ).
16
F ig u re 14.
H aptophilicity in v o lv in g th e m ethoxy g ro u p .
Gula a n d S p e n c e r28 illu s tra te a sim ilar a n c h o rin g e ffe c t fo r th e e s te r
fu n ctio n al g ro u p an d its c o rre sp o n d in g s a lt.
ste re o se le c tiv e
re d u c tio n
d u rin g
cata ly tic
T his is illu s tra te d in th e
h y d ro g e n a tio n
of
10-
carb o m eth o x y -tr a n s - d ecal- 2 -one (F ig u re 1 5 ).
F ig u re 15. .H aptophilicity in v o lv in g th e e s te r g ro u p .
W ilkening29 -30
u s e d th is d ire c tiv e a b ility of th e e s te r g ro u p in th e
re d u c tio n of 2 -m eth y len e-c is - l , 5 -d ic a rb o x v m e th v ir4 .3 .O loctane (F ig u re 1 6 ).
T his w as u s e d as a k e y s te p in h is stereo sp e cific s y n th e s is of (d l)
m odehephene.
\
17
H3C
COOMe
LLx
<P
H3C
■
H2
P d /C
—
C
L
(Z
COOMe
C OOMe
F ig u re 16. S tereo sp ecific h y d ro g e n a tio n of 2 -m e th y le n e -c is -l,5 d icarboxym ethyl[ 4 .3 .0 ] o c ta n e .
Palladium Prom oted Bond Isom erization in Cyclic System s
Palladium h a s lo n g b e e n know n to prom ote th e b o n d isom erization in
cyclic sy ste m s, a n a b ility w hich h a s b e e n show n to b e g r e a te r th a n th a t of
th e o th e r noble metal c a ta ly s ts , ie . irid iu m , ru th e n iu m , rh o d iu m , osmium,
iridium , an d p la tin u m .31’? 2
T h e re fo re palladium is fr e q u e n tly u se d w hen
b o n d isom erization an d m igration a re w a n ted ; platinum w hen th e y a re to b e
a v o id e d .33
A u g u stin e 34
m easured
th e
am ount
of
bond
isom erization
of
m eth y len ecy clo h ex en e, 3 -m eth y lcy clo h ex en e, an d 4 -m ethylcyclohexene to
m ethylcyclohexene in eth an o l o v e r 5% P d (F ig u re 17).
A t 25% com pletion,
he fo u n d 100%, 34%, a n d 37%, re s p e c tiv e ly , of m ethylcyclohexene in th e
olefinic fr a c tio n .
18
F ig u re 17. Palladium prom oted bo n d isom erization in th e
m ethylcyclohexene sy stem .
T heodore o b se rv e d b o n d isom erization w ith palladium as w ell.
D u rin g
h y d ro g e n a tio n stu d ie s of [1] w ith P d / C c a ta ly s t, he o b se rv e d fiv e p eak s in
th e gas chrom atogram u s e d to m onitor th e rea ctio n !
able
to
com pletely
c h a ra c te riz e
all th e
p ro d u c ts
A lth o u g h h e was n e v e r
re s u ltin g
from th is
isom erization, T heodore b elieved th e y w ere th e re s u lt of th e co n tin u ed
isom erization of [1] (F ig u re 18).
P d /C
F ig u re 18. Palladium in d u c ed b o n d isom erization of c is -8oxabicyclo[ 4 .3 .0 ]n o n -3 -e n e .
19
Scope a n d Goals of th is In v e stig atio n
A lthough a n u m b er of o b serv atio n s h av e b e en made b y th e M undy
g ro u p s u g g e s tin g o x y g e n 's role in im p a rtin g re a c tiv ity a n d s tr u c tu r e on th e
molecule, m any q u e stio n s rem ain.
In d e e d , a g ro u p d is c re p a n c y e x is ts .
Is
th e re oxygen p a rtic ip a tio n in oxy m ercu ratio n of [ 1 ] a s Q tz e n b e rg e r re p o rts
o r a re
simple s te ric fa c to rs solely re sp o n sib le in in flu e n c in g p ro d u c t
ste re o c h e m istry a s W ilkening concludes?
p r e f e r r e d conform ation of [ I ] ?
[7]?
Is conform ation [1A] a c tu a lly th e
What th e n is th e p r e f e r r e d conform ation of
Is o x y g e n 's a ffin ity fo r c a ta ly s t re a l as o b se rv e d b y T heodore an d
Glancy?
Can th is p ro p o se d a ffin ity b e d e te c te d in new sy stem s?
th e b a sis of th e b o n d isom erization re p o rte d b y T heodore?
What is
W here else can
we s e a rc h fo r o x y g e n 's ro le in im p a rtin g re a c tiv ity in th e s e system s?
To a d d re s s th e above q u e stio n s th e following in v e stig a tio n s w ere
p ro p o se d .
(1)
S u b ject
[1]
and
[7]
to
h y d ro b o ra tio n ,
e p o x id atio n ,
an d
o x y m e rc u ra tio n /d e m e rc u ra tio n stu d ie s a n d examine th e stereo c h e m istrie s of
th e
p ro d u c ts .
U se
calculational
a p p ro a c h e s,
MM2 a n d
MNDO,
to
in v e stig a te [1] a n d [7] to determ ine th e ir conform ational g ro u n d s ta te
sta b ilitie s a n d
o b se rv e th e HOMO'S of each conform ation to examine MO
e n e rg ie s a n d th e atomic co efficien ts, esp ecially th a t of o x y g e n .
com paring th e
p ro d u c t
s tu d ie s
on
[1]
and
[7 ],
By
com bined w ith th e
calculational inform ation, attem p t to more clearly, d is tin g u is h o x y g e n 's role
in in flu en c in g th e ste re o c h e m istry of th e s e ad d itio n s.
(2)
S y n th esize th e s y n - a n d a n ti-to s y la te s of [1] a n d [7 ].
M onitor
th e k in e tic s of th e solvolysis of these^ to s y la te s , o b ta in in g r a te c o n sta n ts
a n d activ atio n p a ra m e te rs , a n d complete a p ro d u c t a n aly sis of th e re a c tio n .
20
From th is d a ta , determ ine o x y g e n 's ro le in im p a rtin g re a c tiv ity to th e
molecule in so lv o ly sis.
(3)
S y n th esize an d su b je c t to cata ly tic h y d ro g e n a tio n 3-m ethyl-
tricy c lo [ 4 .3 .3 .0 ]u n d e c -3 -e n e .
If
o x y g en is
com plexing w ith
c a ta ly st
(involved in h a p to p h ilic ity ), one would e x p e c t a ste re o se le c tiv e re d u c tio n .
In v e stig a te
th e
re d u c e d
p ro d u c ts
in
an
attem p t
to
o b serv e
th is
oxygen / c a ta ly s t in te ra c tio n .
(4)
C h arac te riz e a n d examine from calculation a p p ro a c h e s (th e MM2
an d MNDO m ethods) th e olefins p ro p o se d in th e palladium in d u c ed bond
isom erization of [ 1 ] in an attem p t to ratio n alize th is p r o c e s s .
(5)
As a new system in w hich to o b se rv e o x y g e n 's role in im p artin g
re a c tiv ity on th e m olecule, elu cid ate th e e le c tro n im pact mass sp e c tro sc o p y
frag m en tatio n m echanism of [ 1 ] , d eterm in in g o x y g e n 's ro le in th is p ro c e s s .
21
CHAPTER 2
RESULTS AND DISCUSSION
O x y g en 's E ffect in In flu en c in g S tereo ch em istry
The s y n th e s e s of [1] an d [7] w ere c a rrie d ou t follow ing th e p ro c e d u re s
of O tz e n b e rg e r 1 6 a n d W ilkening13, re s p e c tiv e ly , an d a re illu s tra te d in
F ig u re 19.
16
I.
LAH/THF
2.
TsC I/p yr.
0
% I
O
HVMeOH
COOMe
I.
COOMe 2-
LDA/THF
BKCH2IjBr
COOMe
1.
LAH/THF
2.
T sC I/pyr.
18
F ig u re 19.
S y n th e sis of Cisr S-O xabicyclot4 . 3 . 0 ]n o n -3 -e n e , [1 ] , an d
o x a tric y c lo [ 4 .3 .3 .0 ] u n d e c -3 - e n e , [7 ].
8
-
In an a tte m p t to d is tin g u is h simple s te r ic e ffe cts from a n y electro n ic
e ffe cts im p arted b y e th e re a l oxyg en in in flu en c in g th e s te re o c h e m istry of
22
electro p h ilic a d d itio n s to th e o lefin , a nu m b er of stu d ie s w ere c o n d u cted on
[1] (T able
8
) .
The re s u lts of th e se s tu d ie s w ere th e n com pared to th e
s tu d ie s co n d u cted on [7] ( Table 9 ).
T able
8
.
P ro d u c t s tu d ie s on cisr 8 -o x a b ic y c lo [4 .3 .0 ]n o n -3 -e n e .
S tu d y
P ro d u c t R atios
sy n -O
a n ti-O
h y d ro b o ra tio n
9
I
epoxidation
4
I
o x ym ercuration (MeOH)*
I
3
o xym ercuration (TH F/H 20)*
I
3
T he re p o rte d stereo c h e m istrie s a re th o se of th e alcohol and
m ethoxy p ro d u c ts .
Table 9.
P ro d u c t stu d ie s on
S tu d y
8
-o x a tric y c lo [4 .3 .3 .0 1 u n d e c -3 - e n e .
P ro d u c t R atios
sy n -O
a n ti-O
h y d ro b o ra tio n
I
I
epoxidation
I
I
o x ym ercuration (MeOH)*
I
I
o xym ercuration (THFZH 2 O)
-
-
The re p o rte d stereo ch em istries a re th o se of th e m ethoxy p ro d u c ts .
T he p ro d u c t ra tio s w ere o b tain ed from p e ak in te g ra tio n s of th e GLC
tra c e s ob tain ed on th e VG MMl6 mass sp e c tro m e te r.
T he
re la tiv e
stereo c h e m istrie s of th e alcohols d e riv e d from [1] an d re p o rte d in Table
8
23
w ere determ ined from th e X -ra y c ry s ta l s tr u c tu r e o b tain ed fo r th e s y n to s y la te ,
[1 9 ],
d e riv e d from [1]
(F ig u re 32).
When th is to sy la te was
su b je c te d to saponification (KOH in a b so lu te eth an o l) only one alcohol
re s u lte d , th e c o rre sp o n d in g sy n -a lco h o l. [5 ].
T his alcohol re a c te d w ith
T sC l
d eterm in ed
in
p y rid in e
sp e c tro s c o p y ,
saponification
to
p ro v in g
(F ig u re
reform
th a t
20).
only
[19]
as
ste re o c h e m istry
was
by
nH NMR
m aintained
upon
T he o th e r alcohol, h a v in g a sim ilar GLC
re te n tio n tim e, m ass s p e c tra l frag m en tatio n p a tte r n , an d 1H NMR s p e c tra
was obvio u sly th e c o rre sp o n d in g a n ti- alcohol, [ 6 ] .
P
HO .
HO
5
6
KOH/EtOH
T sC I/pyr.
F ig u re
2 0
.
D eterm ination of th e s te re o c h e m istry of th e sy n -alco h o l of
[ 1 ].
T he epoxide isom ers re s u ltin g from th e epoxidation s tu d y of [1 ], w ere
cleanly collected b y p re p a ra tiv e GLC (13% DECS, l O 'x l / l " ) .
When th e
m inor epoxide isom er, th e f ir s t p e ak to e lu te , was re d u c e d w ith LAH in
te tr a h y d r o f u r a n , only th e s y n -alco h o l, [5 ] , was ob tain ed as d eterm in ed b y
24
its re te n tio n time a n d frag m en tatio n p a tte r n .
The
second p e a k , th e major
epoxide isom er, was sim ilarly re d u c e d y ie ld in g only th e a n ti- alcohol. [ 6 ],
again d eterm in ed b y its re te n tio n time a n d frag m en tatio n p a tte r n .
B ecause
s te re o c h e m istry is m aintained in th e re d u c tio n of e p o x id e s , 3 5 - 3 6 the minor
p ro d u c t was d eterm in ed to b e th e sy n -e p o x id e . [ 2 0 ], an d th e major p ro d u c t
th e a n ti- e p o x id e. [ 2 1 ] .
20
21
A d iffe re n c e n u c le a r O v e rh a u se r e ffe c t (NOE ) 3 7 1H NMB experim ent
was em ployed to determ in e th e id e n titie s of th e m ethoxy iso m ers, re s u ltin g
from th e m eth o x y m ercu ratio n / d em ercu ratio n s tu d y of [ 1 ] a n d re p o rte d in
Table
8
. Again th e isom ers w ere clean ly collected b y p r e p a r a to r y GLC (13%
DEGS, 1 0 x 1 /4 "). T he xHNMR s p e c tra of th e major p ro d u c t, th e second to
e lu te , re v e a le d a one p ro to n m ultiplet a t 3.17
irra d ia te d a s ig n ific a n t p o sitiv e
8
.
When th is signal was
7.1 % NOE enhancem ent
th e axial r in g ju n c tu re p ro to n re s o n a tin g a t 2.18
8
was o b serv ed a t
(F ig u re 21).
T his
enhancem ent is th e r e s u lt of th e close sp ecial p ro x im ity of th e two p r o to n s .
In th e o th e r isom er, w hen th e c o rre sp o n d in g one p ro to n m u ltip let a t 3.25
8
was ir r a d ia te d , no NOE enhancem en t of th e r in g ju n c tu re p ro to n s was
o b s e rv e d .
T h e re fo re , th e major p ro d u c t was d eterm in ed to b e th e s y n -
m ethoxy iso m er, [ 2 2 ] , an d th e m inor p ro d u c t was d eterm in ed to b e th e a n tim ethoxy isom er, [2 3 ].
25
T xC
MeO
MeO
22
23
17.
F ig u re 21. % enhancem ent of NOE e x p erim en t on th e s y n -m eth o x v d e riv a tiv e
of c i s j 8 -oxataicyclo[ 4 .3 .0 ]n o n -3 -e n e .
T he a b so lu te stereo c h e m istrie s of the^ alcohols a n d ep o x id es d e riv e d
from [7] an d re p o rte d in T able 9 w ere sim ilarly d e term in e d .
An X -ra y
s tr u c tu r e fo r s y n -to s y la te , [2 4 ], d e riv e d from [7] was o b ta in e d (F ig u re 32).
When
th is
to sy la te
was
su b je c te d
to
saponification
re s u lte d , th e c o rre sp o n d in g sy n -a lco h o l. [2 5 ].
o n ly
one
alcohol
A gain, [25] re a c te d w ith
p a ra -to lu e n e su lfo n y lc h lo rid e in p y rid in e to form only [2 4 ], as determ in ed b y
1H NMR s p e c tro s c o p y , p ro v in g th a t ste re o c h e m istry was m aintained u p o n
saponification
(F ig u re
22).
T he o th e r alcohol, h a v in g a sim ilar GLC
re te n tio n tim e, m ass sp e c tru m , a n d 1H NMR sp e c tru m , was th e re fo re th e
a n ti- isom er, [2 6 ].
26
KOH/EtOH
T sC I/pyr.
F ig u re 22. D eterm ination of th e ste re o c h e m istry of th e sy n -alco h o l of
8 -oxatricyclO [ 4 .3 .3 .0 ]u n d e c -3 e n e .
T he epoxide iso m ers, re s u ltin g from th e epoxidation s tu d y of [7 ], w ere
cleanly collected b y p re p a ra tiv e GLC (13% DEGS, IO1* ! / 4 " ).
When th e f ir s t
epoxide isom er to elu te was re d u c e d w ith LAH, p u re sy n -a lc o h o l, [2 5 ], was
o b ta in e d .
When th e second epoxide isom er was re d u c e d , o n ly th e a n ti­
alcohol, [2 6 ], was o b ta in e d .
T he sy n -e p o x id e isom er, [ 8 ], a n d th e a n ti-
epoxide isom er, [9 ], w ere th e re fo re c h a ra c te riz e d .
27
W ilkeningia u s e d a n 1H NMR a rg u m e n t to d eterm ine th e id e n titie s of
th e sy n -m e th o x y isom er, [ 1 0 ] , an d th e a n ti-m e th o x y iso m er, [ 1 1 ] , d e riv e d
from [7 ].
T he stereo c h e m istrie s of th e p ro d u c ts re p o rte d in T ab les
all
determ ined
stereo c h e m istrie s
upon
th e
in itial
electro p h ilic
8
a d d itio n .
an d 9 a re
The
of th e p ro d u c ts in th e o x y m e rc u ra tio n /d e m e rc u ra tio n .
s tu d ie s a re th o u g h t to b e b a se d u p o n th e tr a n s ad d itio n of w a ter to th e
m ercurinium ion in te rm e d ia te . 3 8
T he ste re o c h e m istry of th is in term ed iate is
determ ined b y th e in itia l electro p h ilic a d d itio n of m e rc u ric a c e ta te to th e
olefin.
In
c o n tra s t,
th e
ste re o c h e m istry
of th e
p ro d u c ts
from th e
epoxidation a n d h y d ro b o ra tio n stu d ie s a re defin ed d ire c tly b y th e in itial
electro p h ilic a tta c k .
T he s te re o c h e m istry of electro p h ilic a d d itio n s to o le fin s, as H eh re 3 9
re c e n tly r e p o r ts , will ultim ately d ep en d on a t le a st th re e f a c to r s : " ( I ) th e
28
re la tiv e equilibrium a b u n d an c e s of all p o ssib le conform ations of each olefin
(sin ce only th e y will b e p r e s e n t a t equilibrium an d th e re fo re only th e se
minima can r e a c t ) ,
minima, an d
( 2 ) th e re la tiv e re a c tiv itie s of th e s e conform ational
(3) th e s te ro se le c tiv ite s of th e in d iv id u al co n fo rm atio n s."
T h e re fo re , to more c le a rly in te r p r e t th e r e s u lts re p o rte d in T ables
8
and
9
,
each of th e s e fa c to rs m ust b e in d iv id u a lly exam ined.
The MM2 an d MNDO m ethdds w ere em ployed to d eterm in e th e re la tiv e
equilibrium a b u n d an c e s of olefins [1] a n d [7] (fa c to r I ) .
One s tr e n g th of
th e MM2 m ethod is its a b ility to d eterm ine conform ational minima of a
compound b y calc u la tin g s te ric e n e rg ie s fo r all p o ssib le conform ations of
th e m olecule . 4 0
MM2 c o n sid e rs a molecule as a collection o f atoms h eld
to g e th e r b y harm onic fo rc e s w hich can b e d e sc rib e d b y p o te n tia l e n e rg y
fu n c tio n s of s tr u c tu r a l fe a tu re s
su c h a s b o n d le n g th s ,
nonbonded in te ra c tio n s an d so on.
b o n d a n g le s,
T he com bination o f th e s e p o te n tia l
e n e rg y fu n c tio n s c o n stitu te s th e fo rce fie ld .
T he s te ric e n e rg y (ES) of th e
molecule in th e fo rce field a ris e s from d ev iatio n s from "ideal" s tr u c tu r a l
fe a tu re s a n d can b e approxim ated b y a sum of e n e rg y c o n trib u tio n s
ES=Et^ E s,t+Ento+ .........
w here Eb is th e e n e rg y a ris in g from b e n d in g b o n d a n g les from th e ir
ideal
v alu es (ie . all s p 3 b o n d an g les a re 109), Es t is th e e n e rg y a ris in g
from s tre tc h in g b o n d le n g th s from th e ir "ideal" le n g th s (ie . all c arb o n carbon b o n d le n g th s a re 1.54 A ), a n d En b is th e e n e rg y of nonbonded
in te ra c tio n s .
T he s te r ic e n e rg y of th e molecule is , th e re fo re , th e d ifferen ce
in e n e rg y betw een th e a c tu a l molecule a n d a h y p o th e tic al molecule w here
all b o n d le n g th s an d b o n d a n g les h a v e e x a c tly th e ir "ideal" v alu es - 4 1
29
Two global minima w ere o b tain ed fo r each olefin b y th e MM2 m ethod,
c o rre sp o n d in g to th e two a n tic ip a te d b o at conform ations a n d a re re p o rte d in
Tables 10 a n d 11.
The MNDO . m ethod is a sem i-em pirical m olecular o rb ita l calculation
developed b y D ew ar 4 2 an d h a s , as one of its s tr e n g th s , th e a b ility to
a c c u ra te ly calculate h e a ts of form ation (Hf ) while r e q u irin g only m odest
com putational tim e.
T he in itial geom etries fo r th e MNDO calculation w ere
th e optim ized geom etries o b tain ed b y th e MM2 m ethod.
T h ese geom etries
w ere th e n optim ized a t th e SCF level b y minimizing th e e n e rg y w ith th e
D avidon-F letcher-P ow ell (DFP) a lg o rith m . 4 3
T h ese calcu lated e n e rg ie s a re
re p o rte d in T ables 10 a n d 11.
Table 10. G round s ta te conform ational e n e rg ie s fo r c is - 8 oxabicyclo[ 4 .3 .0 ] n o n -3-e n e , [ I ] .
C onform ation
E n e rg y ( K cal/mole)
MM2 (S te ric )
MNDO (Hf )
16.76
-42.90
16.73
-42.84
30
T able 11. G round s ta te conform ational e n e rg ie s fo r
o x a tric y c lo [4 .3 .3 .0 ]u n d e c -3 -e n e , [7 ].
Conform ation
8
-
E n e rg y (K cal/m ole)
MM2 (S te ric )
MNDO (H1f-I
7A
27.39
-48.77
7B
27.24
-48.81
o
o
In a d d itio n to s u g g e s tin g two minima e x ist fo r b o th [1] an d [ 7 ]
(c o rre s p o n d in g to th e two a n tic ip a te d b o a t co n fo rm atio n s), th e se re s u lts
s u g g e s t th a t th e minima fo r each olefin a re e n e rg e tic a lly e q u iv alen t w ithin
th e e r r o r s re p o rte d fo r each c alcu latio n . 3 ® - 4 4
As a r e s u lt, th e re la tiv e
conform ational equilibrium a b u n d a n c e s, a s calcu lated as ex p(-A E /R T ) w here
AE is th e conform ational e n e rg y d iffe re n c e s , R is th e gas c o n sta n t an d
T=298 °K , a re ap p ro x im ately equ al fo r each alk en e.
T h ese conform ational
equilibrium a b u n d a n c e s a re illu s tra te d in F ig u re 23 an d F ig u re 24.
IA
F ig u re 23.
IB
E quilibrium conform ations of S -cis-o x ab icy clo l 4 . 3 . 0 1 n o n - 3 en e.
31
F ig u re 24. E quilibrium Conform ations of
ene.
8
-o x atricy clo [ 4 . 3 . 3 . 0 ]u n d e c -3 -
A n u m b er of a p p ro a ch e s h av e re c e n tly b een d eveloped to in v e stig a te
o le fin /s u b s tra te re a c tiv itie s an d re g io - a n d ste re o s e le c tiv itie s .
a i . 3 7 . 4 5 ,46
H ehre e t
Jiag (JeveJopetJ a re a c tiv ity model b y c o n sid e rin g th e re la tiv e
a ffin ities of th e d ia stro p h ic olefin fa c es tow ard a te s t electro p h ile
p r o to n ) .
(a
T he te s t electro p h ile is m apped onto quantum -m echanical electro n
d e n sity s u rfa c e s of th e olefin an d a n e le c tro s ta tic p o te n tia l is d eterm in ed .
T his e n e rg y a cc o u n ts on ly fo r th e coulombic in te ra c tio n s b etw een a p o in t
c h a rg e (th e p ro to n ) a n d th e s u b s tr a te , b u t h as p ro v e n to b e a c c u ra te in
p re d ic tin g th e re g io - a n d s te re o c h e m istry of a n u m b er of electro p h ilic
a d d itio n s to allylie double b o n d s .
T h is a p p ro a c h is q u a lita tiv e ly sim ilar to
atte m p ts to calculate th e e le c tro p h ile /s u b s tra te "superm olecule" a t sele c t
geom etries.
H ouk 4 7 ’ 4 8 a n d o th e rs h a v e attem p ted to calcu late d ire c tly th e
p ro p e rtie s of tra n s itio n s ta te s .
T his a p p ro a c h h as th e a d v a n ta g e s th a t no
assum ptions h a v e to b e m ade, b u t is p r e s e n tly lim ited in its ap p licatio n s to
v e ry simple sy ste m .
B ecause
of
its
sim plicity
an d
e leg an ce,
we
chose
th e
F ro n tie r
M olecular O rb ita l 4 8 (FMO) th e o ry to p re d ic t th e re la tiv e re a c tiv itie s (fa c to r
32
two) of each conform ational isom er e x is tin g in equilibrium fo r [1] an d [7 ].
Within th e fram ew ork of th e FMO model, th e re a c tiv ity of a olefin to w ard s
an electro p h ile sh ould in c re a se w ith d e c re a sin g e n e rg y s e p a ra tio n betw een
th e olefin HOMO an d th e LUMO on th e elec tro p h ile.
Since LUMO of th e
electro p h ile rem ains c o n sta n t fo r each s tu d y , th is re la tiv e re a c tiv ity should
p a ra llel th e re la tiv e HOMO e n e rg ie s , w hich a re re p o rte d in T able 12 an d
Table 13.
Table 12.
HOMO conform ational e n e rg ie s of c is -8 -o x a b ic v c lo l4 .3 .O lnon-3ene.
Conform ation
I
E n e rg y (eV )
IA
-9 .9 6
IB
. -9 .9 4
Table 13. HOMO conform ational e n e rg ie s of 8 -o x a tric y c lo [ 4 . 3 . 3 . 0 ]u n d e c3-en e.
Conform ation
E n e rg y (eV )
7A
-9.69
7B
-9 .6 9
The above calculations s u g g e s t th a t conform ation [1A] a n d [IB ] h av e
n e a rly id en tic al re a c tiv itie s aind conform ations [7A] a n d [7B] h av e id en tical
re a c tiv itie s .
T he s te re o c h e m istry of electro p h ilic a d d itio n s to o le fin s, b a se d on
FMO th e o ry , assum es th a t electro p h ilic a tta c k will o ccu r w here th e u -b o n d
33
is most heavily c o n c e n tra te d .
Such an a p p ro a c h ,
h o w ev er, does not
d is tin g u is h th e d ia stere o to p ic faces of th e o le fin s, su c h a s [1] an d [7 ],
h a v in g sym m etrical Ti-b o n d s .
in d iv id u a l conform ations
d ifferen c es
To exam ine th e s te re o se le c tiv itie s of th e
(fa c to r t h r e e ) , we a ttem p ted to examine a n y
th e e lec tro p h ile "ex p e rie n c es"
betw een th e two d ia stere o to p ic
faces of th e n -b o n d in th e g ro u n d s ta te b y exam ining th e e n tire HOMO of
each conform ation.
On th e b a se s of h a rd a n d so ft acid b ase (HSAB)
th e o rie s 50, e lectro p h ilic a tta c k on olefins is g o v e rn e d b y th e Coulombic
in te ra c tio n s betw een re a c ta n t an d s u b s tr a te a t th e re a c tiv e site (c h a rg e
control) an d th e in te ra c tio n s betw een occupied m olecular o rb ita l of th e
olefin an d th e un o ccu p ied m olecular o rb ita l of th e e lec tro p h ile (o rb ita l
c o n tro l).
A ccording to HSAB th e o ry , a so ft acid (e le ctro p h ile ) is most
lik ely to in te ra c t a t th e p o s itio n (s) w ith th e la rg e s t c o e f f ic ie n ts ) , ie.
o rb ita l c o n tro l, while a h a rd b ase (n u cleo p h ile) will a tta c k th e m ost p o sitiv e
c e n te r, ie c h a rg e c o n tro l. B ecause d ib o ran e an d H g(O A c)2 a re classified as
so ft acid s (o r s o ft elec tro p h iles) an d mCPBA is classified a s a h a rd so ft
acid
(e le c tro p h ile )51,
o rb ita l
co n tro l
sh o u ld
g o v e rn
th e s e
ad d itio n s.
T h e re fo re , th e e n tire HOMOs of th e olefins w ere exam ined to see if th e re
w ere
la rg e
c o effic ien ts,
especially
on
th e
o xygen
atom ,
th a t
could
fa v o ra b ly in te ra c t w ith th e e lec tro p h iles a n d th u s d ire c t th e a d d itio n .
34
F ig u re 25. HOMO c o n to u r p lo ts of 8 -c is -o x a b ic y c lo [4 .3 .0 ]n o n -3 -e n e .
F ig u re 26. HOMO c o n to u r p lo ts of 8 -o x a tric y c lo [4 .3 . 3 . 0 ]u n d e c -3 -e n e .
In exam ining th e c o n to u r p lo ts of th e HOMOs fo r [1 A ], [ I B ] , [7 A ],
an d
[7 B ], it is obvious th a t no co efficien ts e x ist on o xygen in a n y
conform ation.
As
a
r e s u lt,
c o n sid e rin g
b o th
conform ers
e x ist
in
eq uilibrium , th e re a p p e a rs to be no d ifferen c es in w hat th e electro p h ile
"ex p e rie n c es"
betw een th e two faces of th e n -sy ste m fo r [1] o r [7 ].
35
From
an
exam ination
of Table
11,
it
a p p e a rs
th a t
in
[7]
two
conform ational minima e x is t in eq u ilib riu m , [7A] an d [7 B ], in approxim ate
equal a b u n d a n c e .
T h ese conform ers h a v e HOMO's of e q u al e n e rg y a n d ,
th e re fo re sh o u ld h av e eq u al re a c tiv itie s (T ab le 13).
It also a p p e a rs th a t
th e se conform ers h a v e no c o n trib u tio n b y o x y g en (w hich could p o ssib ly hav e
d ire c te d e lectro p h ilic a d d itio n s) in th e ir HOMO’S (F ig u re 26).
faces
of
[7]
h av e
id e n tic al
s te r ic
en v iro n m en ts
Since th e n -
(c o n sid e rin g
b o th
conform ations e x is t in equilibrium fo r th e m olecule), from th e s e combined
d a ta , th e re is no re a so n to p re d ic t a n y ste re o se le c tiv e ad d itio n s to [7 ]. Not
s u rp ris in g ly , a complete ab se n c e of s te re o s e le c tiv ity is o b s e rv e d (T able 9 ).
In [1 ], a g a in , it a p p e a rs th a t two conform ational minima e x ist in
eq uilibrium , [1A] an d [ I B ] , in approxim ate equal a b u n d an c e s (T able 10).
FMO th e o ry p re d ic ts th e s e conform ers to h av e n e a rly e q u al re a c tiv itie s
(T able 12) an d a g a in , th e re a p p e a rs to b e no c o n trib u tio n b y oxygen (to
p o ssib ly
d ire c t
electro p h ilic
a d d itio n s)
in
th e .
HOMO
of
e ith e r
conform ation.
T h e re a r e , h o w ev er, obvious s te r ic d ifferen c es betw een, th e n -fa c e s of
[I].
In [ I B ] , th e face a n ti to o x y g e n .is much le ss h in d e re d a n d th e in itial
electro p h ilic a tta c k a n ti to oxygen would a p p e a r to b e fa v o re d .
th e
Ti -fac es
In [LA],
a re also d issim ilar. E lectrophilic a tta c k on th e face sy n to
oxygen " e x p e rie n c e s’1 two p se u d o -a x ia l p ro to n s a to th e d o uble b o n d an d an
oxapropano r in g a t th e B p o sitio n s,
while a tta c k on th e face a n ti to
oxygen "ex p e rie n c es" two p se u d o -e q u a to ria l p ro to n s a to th e double b o n d
a n d two r in g ju n c tu re p ro to n s B to th e double b o n d in c o n tra d istin c tio n .
As a r e s u lt, th e face a n ti to oxyg en in [LA ], a g a in , a p p e a rs to b e th e le ss
ste ric a lly h in d e re d face an d in itia l electro p h ilic a tta c k a n ti to o xygen
36
a p p e a rs
to
be
fa v o re d .
Not
s u rp ris in g ly .
T able
8
illu s tra te s
some
s te re o s e le c tiv ity in w hich in itial e lectro p h ilic a tta c k a n ti a p p e a rs to b e
fa v o re d .
A t f ir s t glance th e re s u lts re p o rte d in T able 8 a p p e a r in c o n siste n t.
In th e h y d ro b o ra tio n an d epoxidation s tu d ie s com pleted on [1 ] , th e major
p ro d u c ts a re a n ti to o x y g e n , while in th e o x y m e rc u ra tio n / d em ercu ratio n
stu d ie s th e major p ro d u c ts a re sy n to o x y g e n .
clarified
by
re c a llin g
th a t
in
T h ese r e s u lts can b e
o x y m e rc u ra tio n /d e m e rc u ra tio n ,
p ro d u c t
ste re o c h e m istry is tr a n s to th a t of th e in itia l e lectro p h ilic a tta c k .
A fte r
form ation of a m ercurinium ion in te rm e d ia te , tr a n s -a d d itio n of e ith e r th e
MeOH of H2O nucleophiles r e s u lts .
T h is p o sitio n s th e m ethoxy o r alcohol
g ro u p s opposite to th a t of th e in itia lly electro p h ilic a tta c k .
th e
h y d ro b o ra tio n
an d
in
th e
ep o x id atio n
s tu d ie s ,
In c o n tra s t, in
th e
re p o rte d
stereo c h e m istrie s a re d eterm ined b y th e in itia l a tta c k of th e e lec tro p h ile.
A lthough Hoffman52 a s e a rly a s 1872 s ta te s th a t " s te ric effects a re
u s e d like p a trio tism b y a sc o u n d re l as a la s t r e s o r t f o r th o se who hav e
d iffic u lty in in te r p r e tin g re a c tiv itie s ” , -----in lig h t of th is in v e stig a tio n ,
it
a p p e a rs
th a t
th e r e
is
no
oxygen
p a rtic ip a tio n
ste re o c h e m istry o f elec tro p h ilic a d d itio n s to [1] o r [ 7 ] .
iTiflmemming th e
T h e o b s e rv e d
s te re o s e le c tiv ity in [1] a p p e a rs to be th e r e s u lt of sim ple s te r ic e ffe c ts .
T hese fin d in g s a re c o n siste n t w ith th o se re p o rte d b y W ilkening (F ig u re 10)
an d seem to r e fu te th e p ro p o se d o x y g en stab ilize d in term ed iate su g g e s te d b y
O tz e n b e rg e r in th e oxym ercurataio n of [1] (F ig u re 8 ).
37
O x y g en 's E ffect in In flu en c in g R ea c tiv ity
T he se rie s of com pounds in F ig u re 27 w ere d e sig n e d to attem p t to
elucidate th e ox y g en atom 's role in in flu e n c in g re a c tiv ity in so lv o ly sis.
In
th is se rie s th e a n ti- com pounds, [A] a n d [C ], could u n d e rg o a conform ational
flip th a t places th e le av in g g ro u p in a p se u d o -e q u a to ria l p o sitio n (F ig u re
28).
T his would b e e x p ec te d to r e s u lt in oxygen b e in g in r a th e r close
special pro x im ity to th e carb o n atom b e a rin g th e le av in g g ro u p .
Sim ilarly,
a conform ational flip of th e s y n - com pounds, [B ] an d [ D ], would place th e
le av in g g ro u p in p s e u d o -e q u a to ria l p o sitio n s (F ig u re 29) . In th e case of [ B ] ,
th is would r e s u lt in th e carb o n b e a rin g th e le av in g g ro u p b e in g in close
special p ro x im ity to th e two r in g ju n c tu re p ro to n s .
While in th e case of
[D ], th e c arb o n b e a rin g th e le av in g g ro u p would b e in close special
prox im ity to a m ethylene g ro u p .
Note th e sim ilarity of com pounds [A] an d
[ C ] , in th is b o a t conform ation, to th e c o rre sp o n d in g n o rb o rn y l analog in
w hich Wilder o b se rv e d s u b tle NGP b y o x y g en (T able I ) .
One could
th e re fo re im agine NGP e x istin g in com pounds [A] an d [C ] b u t h a v in g no
p o ssib ility of e x is tin g in [B ] an d [ D ] . If NGP is o c c u rrin g , a n in c re ase in
r a te
would
be
p re d ic te d
fo r
th e
s y n -com pounds
re la tiv e
to
th e ir
c o rre sp o n d in g a n ti- a n a lo g u e s.
T he tric y lic to s y la te s ,
[C ] a n d [D ], a re u n iq u e in th a t th e . s te ric
environm ents fo r th e two com pounds a re id en tic al.
In [ C ] , th e tosylate.
g ro u p is s y n to th e p ro p a n o g ro u p w hile in [D] th e to s y la te g ro u p is sy n
to th e oxapropano g ro u p .
T h e re fo re * th e b a ck sid e a tta c k b y so lv en t, on.
th e
to s y la te ,
c arb o n
en v iro n m en t.
b e a rin g
th e
sh o u ld
e x p erien ce
th e
same s te ric
A ny o b se rv e d r a te enhancem ent of [D] o v e r [C ] m ight th e n
be a ttr ib u te d solely to ox y g en p a rtic ip a tio n , If a ra te enhancem ent of th e
38
a n ti- to sy la te s
is
o b s e rv e d ,
th is
would lend s u p p o rt to O tz e n b e rg e r1s
p ro p o se d oxygen NGP in th e o x y m ercu ratio n of [1] (F ig u re 8 ).
L
vs
A
O
L
y -0
vs
D
C
L “ Leaving group
F ig u re 27. Does th e o x y g en atom in flu en ce re a c tiv ity in th e solvolysis
of th e se to sy la tes?
a
c
F ig u re 28. B oat conform ations of a n ti- iso m e rs, [A] a n d [ C ] .
F ig u re 29. B oat conform ations of s y n -iso m e rs, [B ] an d [ D ] .
We in itia lly chose p a r a -n itro b e n z o a te as o u r le a v in g g ro u p .
th e bicyclic com pounds,
To form
[1] was s u b je c t to h y d ro b o ra tio n y ield in g th e
c o rre sp o n d in g alcohol m ixture w hich was su b se q u e n tly c o n v e rte d to th e
39
bieyclic p a r a -n itro b e n z o a te m ix tu re.
A fte r sco res of so lv en t system s w ere
exam ined b y T L C , a m ixture of m ethylene c h lo rid e, e th y l a c e ta te , an d
h ex an es in th e re la tiv e ra tio 20 : I : I : , re s p e c tiv e ly , a ffo rd e d a clean
se p a ra tio n of s y n - a n d a n ti- bieyclic p a r a -n itro b e n z o a te s , [27] a n d [2 8 ],
re s p e c tiv e ly .
F lash ch ro m ato g rap h y was th e n em ployed to isolate th e
p r o d u c ts .
T he s y n th e s e s a n d isolation of th e trie y lic p a r a -n itro b e n z o a te s , w ere
id en tical to th a t of th e bieyclic p a r a -n itro b e n z o a te s . e x c e p t th e in itial
alkene in th e s y n th e s e s was [7 ]. T h is p ro c e d u re y ield ed th e isom erically
p u re
syn-
and
a n ti- tric y c lic
p a ra -n itro b e n z o a te s ,
[29]
an d
[3 0 ],
re s p e c tiv e ly .
U n fo rtu n a te ly , th e se p a r a -n itro b e n z o a te s p ro v e d to b e s u rp ris in g ly
s ta b le .
T h e y would n o t u n d e rg o solvolysis in 80% aq u eo u s a ce to n e , ev en
w hen th e re a c tio n was atte m p ted in sealed tu b e s a t te m p e ra tu re s as h ig h
as 250 °C o v e r a p e rio d of 48 hours'.
T he 80% aqu eo u s aceto n e so lv en t sy stem w as, in itia lly , th e system of
choice.
assum ed
We in te n d e d to complete p ro d u c t stu d ie s on each compound an d we
th e
c h a ra c te riz e d ,
c o rre sp o n d in g
alco h o ls,
w ould b e
major p ro d u c ts
th e
re s u ltin g from an elim ination p ro c e s s .
w hich
had
been
along w ith
p re v io u s ly
th e
alk en es
T h e re fo re , in th is so lv e n t sy stem , we
believ ed th e p ro d u c t a n a ly sis would b e q u ite sim ply accom plished.
In o rd e r to in c re a s e th e re a c tiv ity of th is s e r ie s , we com pleted two
new s y n th e s e s d e riy a tiz in g th e alcohols w ith to s y la te , a b e tte r org an ic
le av in g g ro u p .
U n fo rtu n a te ly , th e . so lv e n t system w hich a ffo rd e d fla sh
se p a ra tio n in th e case of th e p a r a -n itro b e n z o a te s , y ie ld e d no sep a ra tio n
w ith
th e se
to s y la te s .
A gain,
m any ad d itio n al so lv e n t sy stem s
w ere
40
in v e stig a te d b y TLC b u t none w ere fo u n d w hich p ro d u c e d a s e p a ra tio n .
We th e re fo re p ro p o se d th e follow ing s y n th e tic schem es to o btain th e
isom erically p u r e to s y la te s .
In th e s y n th e s e s of th e s y n - to s y la te , [1 9 ], an d
a n ti- to s y la te , [3 1 ], d e riv e d from cis-8 -o x a b icy c lo [4 . 3 . 0 1 n o n -3 -en e . [1] was
su b je c te d to h y d ro b o ra tio n to yield th e c o rre sp o n d in g alcohol m ix tu re which
was s u b s e q u e n tly c o n v e rte d to th e p a r a -n itro b en z o a te d e riv a tiv e s .
F lash
ch ro m ato g rap h y was th e n em ployed to clean ly s e p a ra te th is m ix tu re into
[27] an d [2 8 ].
Saponification of th e isom erically p u re s y n - a n d a n ti- p a r a -
n itro b en z o ates
a ffo rd e d
th e
re s p e c tiv e
m aintained th e ir isom eric p u r ity .
to [19] an d [3 1 ].
s y n - an d a n ti- alcohols w hich
T he alcohols w ere th e n e a sily c o n v erted
F ig u re 30 outlin es th e s e s y n th e s e s .
CC* r f e JCD
H2O2. OH' H
0 ^ \ y
PNBCI
Pyr"
'
m
PNBO
2 7 .2 8
I
flash sep aratio n
/Ce=
KOH
X O CC--XC*
KOH
■
o
TsO
TsCI
>
^ 31
Pyr-
HO
E tO H
EtOH
PN 0 o “
CC=
PNBO
F ig u re 30. S y n th e se s of s y n - an d a n ti- to sy la te s d e riv e d from [1]
41
T he s y n th e s e s of sy n -3 -to sy l-S -o x a tric v c lo F 4 .3 . 3 . O lu n d ecan e. [2 4 ], an d
a n ti- 3 - to s y l-8-o x a tric y c lo [ 4 .3 .3 .0 ] u n d e c a n e , [3 2 ], w ere id e n tic al to th a t of
th e bicyclic se rie s e x c e p t th e in itial alk en e in th e s y n th e s is was [7 ], as is
shown in F ig u re 31.
F ig u re 31. S y n th e se s of s y n - an d a n ti- to sy la te s d e riv e d from [7 ].
T o sy lates [19] an d [24] w ere w hite so lid s , w hich a f te r a num ber of
c ry stalliza tio n a tte m p ts y ield ed c ry s ta ls in h ex an e an d dichlorom ethane (50
: I , re sp e c tiv e ly ) from w hich x - r a y s tr u c tu r e s w ere o b ta in e d . T his x - r a y
d a ta confirm ed th e re la tiv e stereo c h e m istrie s re p o rte d fo r th e to sy la te s (a n d
th e c o rre sp o n d in g alcohols from w hich th e y w ere d e riv e d ) in th e s y n th e s e s .
T h e ir ORTEP d raw in g s a re illu s tra te d in F ig u re 32.
Note th e sim ilarity of
th e conform ations fo r each to s y la te . U n fo rtu n a te ly , to sy la te s [31] an d [32]
w ere oils w hich would n o t, even a f te r co n sid erab le e f f o r t, c ry s ta liz e .
42
F ig u re 32.
ORTEP d raw in g s of th e x - r a y s tr u c tu r e s of [19] an d [24].
An attem p t a t solvolyizing th e to sy la te s in 80% aq u eo u s acetone was
accom plished, b u t only a f te r re flu x in g th e reactio n p e rio d fo r a p erio d of
se v e ra l d a y s.
O btain in g k in e tic d a ta o v e r se v e ra l h a lf-liv e s of su c h a slow
p ro c e ss was d iffic u lt, so o th e r so lv en t sy stem s w ere in v e s tig a te d .
We d isco v e re d th a t in 50% aq u eo u s m ethanol, a so lv en t system w ith a
h ig h e r d ie le ctric c o n sta n t a n d a h ig h e r ionizing pow er p a ra m e te r, Y, and
n u cleophilicity p a ra m e te r, N, th e re a ctio n s p ro ceed w ithin h o u r s .53
T his
solvent system was th e n u s e d to complete all th e solvolysis ex p erim en ts.
It was assum ed th a t th e s u b s titu tio n p ro d u c ts would b e th e p re v io u sly
c h a ra c te riz e d
alcohol an d
m ethoxy com pounds, g re a tly sim plifying th e
p ro d u c t s tu d ie s .
T he
k in e tic
stu d ie s
w ere
com pleted
c o n d u c trim e tric a lly .
A
conductance cell an d th e rm isto r w ere in te rfa c e d 54 to a co m p u ter allowing
fo r th e sim ultaneous acq u isitio n of c o n d u ctan ce, te m p e ra tu re , and time
m easurem ents.
A s ta n d a rd solution of 50% aqueous m ethanol was p r e p a r e d .
The s ta n d a rd solution (25 ml) was ad d ed to th e p r e tre a te d co n d u ctan ce cell
which was th e n placed in th e c o n sta n t te m p e ra tu re b a th .
T he te m p e ra tu re
43
was allowed to e q u ilib ra te , th e n ap p ro x im ately 2 mg of th e to sy la te w ere
ad d ed to th e cell a n d upon te m p e ra tu re e q u ilib ra tio n , d a ta a cq u isitio n b e g a n .
(T h e in itia l to sy la te co n ce n tra tio n s w ere o n ly K T 3-K T 4 M!)
collected ap p ro x im ately e v e ry second
Data w ere
o v e r 3 to 5 h a lf-liv e s of th e re a ctio n
an d an in fin ity p o in t was o b tained a f te r ap p ro x im ately 15 h a lf-liv e s . L east
s q u a re s tre a tm e n t of ln (c _ -c = ) v s time (se co n d s) y ield ed f i r s t o rd e r ra te
c o n sta n ts
(k )
fo r each to s y la te ,
at
th re e
te m p e ra tu re s
d iffe rin g b y
approxim ately 14° C . T he A rrh e n iu s eq u atio n was u s e d to o b tain e n erg ies of
a ctiv atio n (Ea ) a n d th e activ atio n complex th e o ry was em ployed to ob tain
th e e n th a lp y (4SH ) an d e n tro p y (4S S ) of a ctiv atio n .
T he re s u lts of th e se
s tu d ie s a re re p o rte d in T ables 14-16.
Table 14.
K inetic r e s u lts of th e 50% a q u eo u s m ethanolysis of [191 and
[31].
Compound
Temp. (0C) * . 03
k x IO4 Cs*')
R
35, 84
0 .6 0 7
1 .0 0 0 0
5 0 .0 0
3. 47
I. 0000
62. 87
1 4 .3
0. 607
0. 9999
50. 20
3. 32
0. 9996
13. 9
26. 2 4 0 .3
1 .0 0 0 0
35. 78
63. 00
E0 (Kcal/m ole)
I. 0000
25. 8 * 0 .3
44
Table 15. K inetic r e s u lts of th e 50% aq u eo u s m ethanolysis of [24] and
[32].
Compound
Temp. (0C) + . 03
k x IO4 Cs-')
R
35. 82
1.91
0. 9999
50. 10
9. 35
0. 9998
Ea (Kcol/m ole)
0
TsO
24
63. 00
3 7 .9
35. 70
2. 90
2 2 .7 + 0 . 3
I. 0000
0. 9999
yO
TsO
32
Table 16.
50. 15
1 4.7
0 .9 9 9 9
6 2 .9 0
5 2 .7
0. 9997
2 1 .9 + 0 . 4
V)
A ctivation p a ra m e te rs of th e 50% aq u eo u s m ethanolysis of
[1 9 ], [3 1 ], [24] an d [3 2 ].
AH,*(Kcol/m ole)
TsO
32
A S^Ceu)
23. 49 + . 2 7
- I . 87 + .B I
2 3 .0 9 + .3 1
- 3 . 18 ♦ . 9 2
22. 10 + . 3 0
- 4 . 11 + . 9 8
21. 37 + .4 1
-5 . 56 ♦ I. 22
45
P ro d u c ts s tu d ie s w ere com pleted b y com bining th e th re e r u n s fo r each
to s y la te , d istillin g off most of th e m ethanol, an d th e n e x tra c tin g th e
re s u ltin g re s id u e re p e a te d ly w ith d ich lo ro m eth an e.
P ro d u c t stu d ie s w ere
com pleted b y com paring re te n tio n tim es a n d mass s p e c tra l frag m en tatio n
p a tte r n s of th e o b se rv e d p ro d u c ts to th o se of th e a u th e n tic sam ples th a t
w ere sy n th e s iz e d
o b tain ed
from
an d
peak
c h a ra c te riz e d p re v io u s ly .
in te g ra tio n s
com pleted
e q u ip p ed w ith a flame ionization d e te c to r.
on
P ro d u c t ra tio s
GLC
c ap illary
w ere
column
O nly p e ak s w ith re la tiv e a re a s
g r e a te r th a n 1% of th e p ro d u c t m ix tu re w ere re p o rte d . T he r e s u lts of th e se
s tu d ie s a re sum m arized in F ig u res 33-36.
t
o
t
o
,0
( 21 %)
I
,0 (37%)
F ig u re 33. P ro d u c t stu d ie s of 50% a q u eo u s m ethanolysis of [1 9 ].
46
CC“
(22%)
I
CC“
(40%)
13
JCD
O
50% aq. MeOH
CD
O (20%)
MeO
22
CD
(18%)
F ig u re 34. P ro d u c t s tu d ie s of 50% a q u eo u s m ethanolysis of [31]
■ f Jf-'"
for.
(54%)
TsO
O
v
33
50X acI- MeOH
(16%)
( 20 %)
HO
F ig u re 35. P ro d u c t S tu d ies of 50% a q u eo u s m ethanolysis of [24]
■ 47
10
F ig u re 36. P ro d u c t s tu d ie s of 50% aq u eo u s m ethanolysis of [3 2 ].
From a n exam ination of th e r a te c o n sta n ts o b tain ed from th e bicyclic
to s y la te s , th e re a p p e a rs to b e no r a te enhancem ent of [31] o v e r [1 9 ].
The
re la tiv e r a te of [3 1 ]/[1 9 ] is 1.00 a t 3 5 .8°C an d th e e n e rg ie s of activ atio n
fo r th e two to s y la te s a re eq u al w ithin a s ta n d a rd d ev iatio n .
T he g ro u n d s ta te e n e rg ie s of th e s y n - an d a n ti- b icv clic to sy la tes
a re also b eliev ed to b e id e n tic al.
T h ese to sy la te s w ere modelled as th e ir
c o rre sp o n d in g alcohol a n d m ethoxy d e riv a tiv e s , in c h a ir conform ations.
In
each case no sig n ific a n t e n e rg y d iffe re n c e s w ere o b se rv e d b etw een th e s y n an d a n ti- isom ers (T able 17).
48
T able 17.
Modelled bicyclic to sy la te e n e r g ie s .
Compound ■
MM2 ( S te ric Enererv)
MNDO (H„)
5
10.25
-106.54
6
10.26
-106.53
22
11.47
-111.76
23
11.31
-111.62
T he p ro d u c t a n aly se s fo r b o th com pounds a p p e a r to b e d ire c tly
re la te d as well.
In each case th e re is a m ix tu re of a lk e n e s, [1] an d [1 3 ], in
th e approxim ate re la tiv e ra tio of 40 : 20 an d th e m ethoxy an d alcohol
com pounds,
re s u ltin g w ith complete in v e rsio n of c o n fig u ra tio n , in th e
approxim ate re la tiv e ra tio of 20
20.
No d ire c t s u b s titu tio n w ith complete
re te n tio n of c o n fig u ra tio n is o b se rv e d fo r e ith e r to s y la te . T his s u g g e s ts no
fre e carbocation is form ed in th e se re a c tio n s ; th e re a c tio n s a p p e a r to
ex h ib it no classic SnI c h a ra c te r.
T he p ro d u c t stu d ie s fo r th e b icy clic se rie s a re c o n siste n t w ith a
num ber
of
solvolysis
to s y la te s .55-56’57
stu d ie s
com pleted
on
s u b s titu te d
cyclohexyl
In th e se p ro c e ss e s a n intim ate ion p a ir (IIP )58 is
b elieved to b e form ed in th e r a te d e term in in g s te p , followed b y s u b se q u e n t
p a rtitio n in g in to v a rio u s re a ctio n p a th w a y s.
T h ese p ro c e ss e s hav e b e en
fo u n d to r e s u lt, p rim a rily , in p ro d u c ts form ed b y s u b s titu tio n (w ith complete
in v e rsio n of c o n fig u ra tio n , c h a ra c te ris tic of th e classic SN2 m echanism ), a n d
elim ination.
In a d d itio n , a sig n ific a n t p o rtio n of s u b s titu tio n p ro d u c ts h av e
b e en fo u n d to r e s u lt from a 1,2 h y d rid e s h if t, p ro d u c ts n o t o b se rv e d in th e
bicyclic s e rie s .
49
From a n exam ination of th e k in e tic d a ta , th e modelled g ro u n d s ta te
e n erg ies of th e bicyclic to s y la te s , a n d th e p ro d u c t a n a ly s e s , th e re a ctio n
p ro files fo r th e solvolysis of [19] a n d [31] a p p e a r to b e v e r y sim ilar, if no t
id e n tic al.
We a r e , th e re fo re , le ft w ith th e conclusion th a t th e re is no
a p p a re n t e ffe c t b y o x y g en in th e solvolysis of [3 1 ].
To ratio n alize th e se d a ta on th e bicyclic to s y la te s , we also envision a
carbocation
re a c tio n .
in te rm e d ia te
form ed in
th e
r a te
in
th e
T his carb o catio n is d e p ic te d in F ig u re 37 a s an IIP show ing
e x p lic itly on ly one n e a r e s t so lv en t m olecule.
n e g ativ e
d e term in in g s te p
e n tro p ie s
of
in term ed iate (T ab le 1 6 ).
a ctiv atio n
a re
Note th a t th e o b se rv e d
c o n siste n t
w ith
th is
p ro p o se d
In th is d ep ictio n th e cyclohexyl r in g is d raw n in
th e c h a ir conform ation, a lth o u g h its e x a c t conform ation is n o t know n.
A fte r form ation of th e IIP th e r e is p a rtitio n in g in to th e v a rio u s re a ctio n
p a th w a y s.
Elimination of p a ra -to lu en esu lfo n ic acid re s u lts in a m ix tu re of
o lefin s, while s u b s titu tio n b y so lv en t re s u lts in th e com pletely in v e rte d
m ethoxy a n d alcohol p ro d u c ts .
TsO
F ig u re 37. R eaction schem e fo r th e solvolysis of [1 9 ], [2 4 ], an d [31].
50
An exam ination of th e sta b ilitie s of olefins [1] an d [1 3 ], b y MM2 an d
MNDO c alcu latio n s,
in d ic a tes th a t
[13]
is th e therm odynam ically more
stab le alkene b y 2-3 kcal/m ole ( T able 18).
T he Hammond p o stu la te can
th e n be u se d to ratio n alize th e re la tiv e a b u n d an ce of [13] o v e r [1] in th e
elim ination p ro c e s s .
T he tra n s itio n s ta te fo r th e form ation of [13] sh o u ld
b e more sim ilar in e n e rg y a n d s tr u c tu r e to th e IIP th a n in th e case of [1 ].
Table 18.
C alculated olefinic e n e rg ie s (K cal/m o le).
Olefin
MM2 ( S te ric E n e re v )
MNDO (H„)
I
10.14
-4 2 .9 0
13
7.02
-44.47
7
16.77
-48.77
33
.1 4 .7 3
-49.63
In th e tric y c lic s e r ie s , th e re la tiv e r a te of [3 2 ]/[2 4 ] is 1.53 a t 35.8QC.
T his
is
re fle c te d
as
a
approxim ately 800 c a lo rie s.
d ifferen c e
in
th e
e n erg ies
of a ctiv atio n
of
A lth o u g h th is is a su b tle r a te en h an cem en t, it
is s tro n g evidence fo r some form of involvem ent b y th e
o x y g en atom.
T h e re is also a m arked d ifferen c e in th e p ro d u c t a n aly sis of th e two
tricy c lic to s y la te s .
T he p ro d u c ts form ed from [24] a re sim ilar to th o se form ed from th e
bicyclic to s y la te s . In [2 4 ], th e re is a m ix tu re of alk en es [7] a n d [33] in th e
re la tiv e ra tio o f 10 : 50, re s p e c tiv e ly , a n d a m ixture of th e com pletely
in v e rte d m ethoxy a n d alcohol p ro d u c ts in a re la tiv e ra tio of 20 : 20.
a g a in , no re te n tio n of co n fig u ratio n is o b s e rv e d .
Once
T his s u g g e s ts no fre e
carbocations (c h a ra c te ris tic of th e classic SN1 mechanism) a re g e n e ra te d in
51
th e p r o c e s s .
B ecause th e p ro d u c t composition of [24] is sim ilar to th a t of th e
bicyclic to s y la te s , we en vision a re a c tio n seq u en ce like th a t p ro p o se d fo r
[19] an d [31] (F ig u re 37).
A fte r form ation of an in te rm e d ia te ion p a ir in
th e r a te d e term in in g s te p , elim ination of p a r a -to lu en e su lfo n ic acid re s u lts
to from th e olefinic m ix tu re while s u b s titu tio n p ro d u c e s th e com pletely
in v e rte d m ethoxy an d alcohol p ro d u c ts .
A gain MM2 a n d MNDO calculations
re v e a l a therm odynam ic s ta b ility of [33] o v e r [7]
Hammond
p o s tu la te
can
be
used
to
ratio n alize
(T ab le 18) an d th e
th e
re la tiv e
olefinic
abundances.
T he p ro d u c ts r e s u ltin g from [32] co n tain th e m ix tu re of alk en es in a
re la tiv e ra tio of ap p ro x im ately 10 : 50 a n d th e com pletely in v e rte d alcohol
in ap p ro x im ately 20%, p ro d u c ts w hich a re d ire c tly analogous to th e re s u lts
ob tain ed from [2 4 ].
H ow ever, th e com pletely in v e rte d m ethoxy compound is
p re s e n t in only 2% an d a new m ethoxy com pound, [3 4 ], ( a t th e C2 p o sitio n )
a p p a re n tly r e s u ltin g from a 1 ,2 h y d rid e s h ift followed b y s u b s titu tio n e x ists
in 15%.
B ecause th e p ro d u c t s tu d y fo r [32] co n tain ed th e re a rra n g e d m ethoxy
com pound, [3 4 ], a p ro d u c t n o t o b se rv e d in th e solvolysis of th e o th e r
to s y la te s , th e re p ro d u c ib ility of th is s tu d y was q u e stio n e d .
second p ro d u c t a n aly sis was com pleted b y p la cin g [32]
in 50% aqueous
m ethanol a t 50° C. a n d s tir r in g th e so lu tio n o v e rn ig h t.
a n aly sis of th is r u n was id e n tic al to th a t of th e o rig in al.
As a r e s u lt, a
T he p ro d u c t
In a d d itio n , th e re
was a q u e stio n a s to. w h e th e r th e p ro d u c ts o b tain ed from [32] w ere th e
re s u lt of th e a c tu a l k in e tic p ro c e ss o r th e re s u lt of a therm odynam ic
re a rra n g e m e n t o c c u rrin g s u b s e q u e n t to th e k in e tic p ro d u c ts . To a d d re s s th is
52
q u e stio n ,
th e re a c tio n was re p e a te d a th ir d time u n d e r th e id en tical
re a ctio n conditions in w hich a liq u o ts w ere rem oved a f te r 30%, 50%, and 75%
completion of th e re a c tio n .
to th a t of th e o rig in a l.
In each c a se , th e p ro d u c t ra tio s w ere id en tical
T h ese r e s u lts s tro n g ly s u g g e s t th a t th e p ro d u c ts of
th e solvolysis of [32] a re due to a k in e tic p ro c e ss .
By
defin itio n
n e ig h b o rin g
g ro u p
p a rtic ip a tio n
(NGP)
is
th e
stab ilizatio n r e s u ltin g from a s u b s titu e n t b o n d in g to a re a c tio n c e n te r of a n
in term ed iate o r tra n s itio n s ta te .
T his stab ilizatio n ty p ic a l re s u lts in a r a te
enhancem ent, ie . anchim eric a s s is ta n c e .
B ecause th e re is b o n d in g betw een
th e s u b s titu e n t a n d th e re a c tio n c e n te r in NGP,
s u b s e q u e n t ad d itio n s to
th is c e n te r a re d ire c te d b y th is b o n d in g a n d re te n tio n of co n fig u ratio n is
fa v o re d .
In th e p ro d u c t s tu d y , of [3 2 ], no s u b s titu tio n p ro d u c ts w ith re te n tio n
of co n fig u ra tio n a re o b s e rv e d (F ig u re 3 5 ).
As a r e s u lt, it a p p e a rs th a t
th e re is no NGP b y o x y g e n e x is tin g in [3 2 ]; o x y g en is n o t b o n d in g to th e
re a ctio n c e n te r in th e tra n s itio n s ta te o r th e in te rm e d ia te.
If NGP does
not e x is t, w hat th e n c au ses th e o b se rv e d re la tiv e r a te in c re a s e (anchim eric
a ss is ta n c e ) of [32] o v e r [24]?
We do n o t believe th e r a te enhancem ent is d ue to d iffe re n c e s in th e
g ro u n d s ta te e n e rg ie s of th e tric y c lic to s y la te s . A gain, th e s e to sy la te s w ere
modelled as th e ir c o rre sp o n d in g alcohol a n d m ethoxy d e riv a tiv e s in c h a ir
conform ations a n d exam ined b y th e MM2 a n d MNDO m ethods.
In each c ase ,
no sig n ific a n t e n e rg y d iffe re n c e s w ere o b s e rv e d betw een th e s y n - and a n ti­
isom ers
(T able 19).
53
Table 19.
Modelled tric y c lic to sy la te s ta b ilitie s,
Compound
( K cal/ mole) .
MM2 ( S te ric E n erg y )
MNDO
25
20.73
-120.32
26
20.59
-120.38
10
21.78
-115.06
11
21.72
-115.07
An ex p lan a tio n ,
how ever,
(H
f
)
to a cc o u n t fo r th is r a te in c re a se is a
m odification of th e re a c tio n schem e u s e d to d e sc rib e th e solvolysis of [1 9 ],
[2 4 ], an d [3 1 ]. In th e solvolysis of [3 2 ], we ag ain en v isio n a carb o catio n
form ed in th e r a te d eterm in in g s te p , d e p icted a s an IIP show ing ex p lic itly
th e n e a re s t so lv en t molecule (F ig u re 3 8 ). In th e case of [3 2 ], ho w ev er, th e
carbocation is sta b iliz e d , a lb eit s lig h tly , b y th e h y d ro g e n b o n d in g th a t can
e x ist betw een e th e re a l oxygen an d th e h y d ro x y h y d ro g e n of th e so lv en t.
T his stab ilize d IIP is c o n siste n t w ith th e o b se rv e d n e g a tiv e e n tro p y of
a ctiv atio n ob tain ed fo r [32] (T ab le 1 6 ).
A nd th is stab iliza tio n cannot e x ist
in [31] a n d th e re fo re seem s to a cco u n t fo r th e o b se rv e d r a te enhancem ent
in [3 2 ].
A gain a f te r form ation of th e IIP , p a rtitio n in g in to th e v ario u s
re a ctio n p ath w ay s o c c u r s . EUmination of p a r a -to lu en esu lfo n ic acid will once
again r e s u lt in a m ixture of olefins a n d s u b s titu tio n b y so lv e n t a ffo rd s th e
in v e rte d alcohol a n d m ethoxy com pounds.
A 1-2 h y d rid e s h ift followed b y
s u b s titu tio n a cc o u n ts fo r th e m ethoxy com pound a t C2 . B ecau se th e d riv in g
fo rce
to
m igration
in
solvolysis
is
th e
form ation
of a
more
stab le
c a rb o c a tio n ,59 carb o catio n stabiU ties w ere determ in ed b y th e MNDO m ethod.
T h ese calculations iU u stra te a therm odynam ic d riv in g fo rc e p rom oting th is
54
re a rra n g e m e n t.
T he carbocatio n a t C2 is fa v o re d b y ap p ro x im ately 5.
kcal/m ole o v e r th e carb o catio n a t C3 .
F ig u re 38.
T able 20.
P ro p o sed re a c tio n schem e fo r th e solvolysis of [3 2 ].
C alculated carbocation sta b ilitie s (K cal/m ole).
C arbocation
MNDO (H f )
140.32
(*) s ~ p
135.58
"CD
143.38
Co
141.28
55
Many im p o rtan t q u e stio n s w ere an sw ered from th is in v e stig a tio n .
Most n o ta b ly , no NGP was o b se rv e d in th e bicylic o r tric y lic to s y la te s .
T hese d a ta seem to re fu te th e in term ed iate in v o lv in g NGP b y th e o x y g en
atom p ro p o se d b y O tz e n b e rg e r in th e o x y m ercu ratio n of [1] (F ig u re 8 ).
T his in v e stig a tio n h a s g e n e ra te d a n u m b er of in tr ig u in g q u estio n s as
well.
F o r exam ple, if su c h a stab iliza tio n e x ists in [32] w hy does it no t
e x ist in th e closely re la te d [31]?
An exam ination of th e c ry s ta l s tr u c tu r e s
of s y n - to s y la te s , [19] a n d [2 4 ], in d ic a te s n e a rly id en tical s t r u c t u r e s . B oth
com pounds in th e c ry s ta l la ttic e a re in th e c h a ir conform ation w ith th e
to sy late
g ro u p
e q u a to ria l.
B oth to sy la te s
also h av e id en tic al O3-O 1
interatom ic d is ta n c e s , 4.20 ± I A° fo r [24] an d 4.18 ± I A° fo r [19].
One
could assum e th a t th e c ry s ta l s tr u c tu r e s fo r th e a n ti-to s y la te s , [31] an d fo r
[32] would b e as closely re la te d . Why th e n is th e re no t a r a te enhancem ent
in [31]?
P e rh a p s th e ab se n c e of stab ilizatio n in [31] is due to th e d ecrea se d
rig id ity
in
th is
com pound, [3 2 ].
com pound
re la tiv e
to
th e
more
c o n stra in e d
tric y c lic
T he bicyclic com pound e x p erien c e s more conform ational
freedom a n d th e re fo re th e IIP is of h ig h e r e n tro p y . T his is c o n siste n t w ith
th e e n tro p ie s of a ctiv atio n o b tain ed fo r th e bicyclic to s y la te s (T able 16).
T his in c re a se d d is o rd e r may b e re sp o n sib le fo r th e a b se n c e of th e h y d ro g e n
b o n d in g stab iliza tio n .
A n o th er q u e stio n a ris in g from th is s tu d y is , w hy is th e re a 1,2
h y d rid e e x istin g only in [32]?
An exam ination of carb o catio n stab ilitie s
in d ic a tes only a 2 Keal/m ole d riv in g fo rce fa v o rin g th e 1 ,2 h y d rid e s h ift in
th e bicyclic com pounds com pared to a 5 K cal/mole d riv in g fo rce in th e
tric y c lic system (T able 20).
T his d e c re a se d therm odynam ic d riv in g fo rce
56
could p o ssib ly explain th e ab se n c e of th e 1,2 h y d rid e s h ift in th e bicyclie
com pounds, b u t w hat ab o u t th e a b sen ce of th e 1 ,2 s h ift in [24]?
Y et a n o th e r q u e stio n s is , w hy is th e r e only a re a rra n g e d m ethoxy
p ro d u c t an d not th e c o rre sp o n d in g alcohol p ro d u c t in [32]?
Could th e
stab ilize d IIP form ed from m ethanol a n d [32] prom ote th e re a rra n g em e n t?
A tra n s itio n s ta te calculation on th e IIP , could p o s sib ly p ro v id e some
in s ig h t to th is q u e stio n .
T his q u e stio n s rem ain to b e a n sw e re d .
A S e a rc h fo r an O xygen C ataly st In te ra c tio n
T heodore a n d G lancy b o th o b s e rv e d w hat th e y b eliev ed to b e an
o x y g e n /c a ta ly s t
in te ra c tio n .
In a n
atte m p t to
d e te c t th is p ro p o se d
in te ra c tio n in a new sy stem , 3-m e th y l-8 -o x a tric y c lo [4 .3 .3 .0 ]d o d e c -3 -e n e ,
[3 5 ], was sy n th e s iz e d a n d su b jec te d to c ata ly tic h y d ro g e n a tio n .
35
T he rt-faces in [3 5 ], like th e n -fa c e s in [7 ], a re b y d e sig n ste ric a lly
e q u iv a le n t.
One face is s y n to th e p ro p a n o g ro u p while th e o th e r face
ex p erien c e s a n oxapropano g ro u p in c o n tra -d is tin c tio n .
B ecause of th is
s te ric e q u iv alen c e, [35] is a se n sitiv e sy stem in w hich to a tte m p t to d e te c t
an oxygen /c a ta ly s t in te ra c tio n .
If s u c h a n in te ra c tio n e x is ts , one could
e x p ec t a ste re o se le c tiv e re d u c tio n .
57
F ig u re 39 illu stra te s, th e p ro p o se d o x y g e n /c a ta ly s t in te ra c tio n an d th e
re s u ltin g ste re o c h e m istry of th e re d u c e d p ro d u c t.T h is in te ra c tio n would b e
re fle c te d a s a n o b se rv e d isom eric ab u n d an c e of th e a n ti- p ro d u c t.
F ig u re 39.
P ro p o sed o x y g e n /c a ta ly s t in te ra c tio n .
In th e s y n th e s is of [3 5 ], 1.1 e q u iv a le n ts of 1,3 dibrom opropane w ere
added
to
th e
lith iu m
d ie n o la te
of
cis - 1 ,6 - dicarb o m eth o x y - 3 -
m e th y lcy clo h ex -3 -en e, [3 6 ].
T he d ie s te r , [3 7 ], was o b tain ed in h ig h y ie ld .
R eduction
w ith
of
th e
d ie s te r
LAH
a ffo rd e d
th e
diol,
w hich
was
su b se q u e n tly rin g -c lo s e d to th e d e sire d p ro p e lla n e , [3 5 ]. F ig u re 40 outlines
the s y n th e s is .
58
COOMe
35
F ig u re 40. S y n th e sis of 3 -m e th y l-8 -o x a tric y lo [4 .3 .3 .0 ]d o d e c -3 -e n e , [3 5 ].
When [35] was e x p o sed to 10% P t on carb o n c a ta ly s t a t 50 p s i fo r 12
h o u rs , a ste re o se le c tiv e additio n was o b serv ed !
form ed in th e re la tiv e ra tio of 3 : I .
T he re d u c e d p ro d u c ts w ere
T he re a ctio n was com pleted th re e
tim es, each y ie ld in g th e id en tic al p ro d u c t ra tio .
U n fo rtu n a te ly , th e re d u c e d p ro d u c ts w ere se p a ra b le o n ly b y c ap illary
GC/MS a n a ly s is , le av in g th e ste re o c h e m istry of th e major isom er unknow n.
In o rd e r to determ ine th e ste re o c h e m istry
of th e se iso m ers, a sep a ra tio n
schem e will h a v e to b e developed an d m ost p ro b a b ly a two dim ensional NMR
ex perim ent em ployed.
T hese a re te c h n iq u e s w hich a re u n av ailab le to th is
re s e a rc h e r a t th e p r e s e n t time.
As a p rim a ry in v e stig a tio n h o w ev er, th e s e r e s u lts le n d s tro n g s u p p o rt
to th e p ro p o se d o x y g e n /c a ta ly s t in te ra c tio n of T h eo d o re a n d G lancy.
A
ste re o se le c tiv e a d d itio n is th e a n tic ip a te d re s u lt of su c h a n in te ra c tio n .
It
is th e re fo re b eliev ed th a t th e major isom er will b e p ro v e n , a t a la te r d a te ,
to b e th e a n ti- p ro d u c t.
59
An Exam ination of th e Palladium In d u ced Bond Isom erization
of c is-8 -o x a b icy c lo f4 .3 .0 1 n o n -3 -e n e
Palladium h as long been know n to prom ote bond isom erization d u rin g
cata ly tic h y d ro g e n a tio n of cyclic o lefin s.
We have o b se rv e d su ch an
isom erization d u rin g re d u c tio n of c is - 8 -o x ab icv clo f4 .3 .0 1 n o n -3 -e n e .
When
[1]
was
ex p o sed
to
10% Pd
on
[I].
c a rb o n , a t one atm o sp h ere of
h y d ro g e n g a s , ra p id bond isom erization was o b s e rv e d .
F ig u re 41 illu s tra te s
th e com pound(s) e x istin g in th e in itial re a ctio n m ixture ( a ) , th e composition
a t th re e m inutes ( b ) , an d upon complete re d u c tio n a t fifte e n m inutes ( c ) .
A liquots w ere rem oved from th e re a ctio n v essel a t th e v a rio u s times an d
analyzed b y GC/MS.
(a)
J
(b )
(c)
F ig u re 41.
GC tra c e s of th e palladium in d u ced bond isom erization of
c is -8-oxabicyclo[ 4 .3 .0 ]n o n -3 -e n e .
60
F ig u re 42 illu s tra te s a re a ctio n seq u en ce w hich d e sc rib e s th e o b serv ed
bond m igrations an d olefinic re d u c tio n s.
In th is se q u e n c e , [1] isom erizes to
[13]. T h is, in t u r n , re a rra n g e s to [14] w hich s u b se q u e n tly isom erizes to [1 5 ].
In a d d itio n , olefins [1 ] ,
[1 3 ], an d [1 4 ], a re re d u c e d to [1 2 ].
In th e
re d u c tio n of [ 14], h y d ro g e n ad d itio n cis_ to th e r in g ju n c tu re p ro to n also
re s u lts in [1 2 ], while ad d itio n a n ti to th e rin g - ju n c tu re p ro to n re s u lts in
tr a n s -8 -o x ab icy clo [ 4 .3 .0 ] n o n a n e , [1 6 ].
Pd/C
F ig u re 42. B ond m igrations an d olefinic re d u c tio n s of c is - 8oxabicyclo [4 .3 .0 ] non -3 -e n e .
The id e n titie s [1 ] , [1 2 ], [1 3 ], [1 5 ], a n d [16] w ere unam biguously
c h a ra c te riz e d b y com parisons of th e ir re te n tio n times a n d m ass sp e c tra l
frag m en tatio n p a tte r n s to th o se a u th e n tic sam ples. Com pounds [1] an d [13]
w ere p re p a re d b y h e a tin g th e m ixture of [19] an d [31] to 250° C, prom oting
elim ination
of p a r a -to lu en esu lfo n ic
a c id .
Olefins
[1]
p ro d u c e d in th e ra tio of 1 :4 , re s p e c tiv e ly (F ig u re 43).
th e n
cleanly
c h a ra c te riz e d ,
collected
in p a r t ,
by
p r e p a r a to r y
GLC
and
[13]
w ere
O lefin, [13], was
(10% DECS,
10"x^')
an d
b a se d u p o n an aHNMR s p e c tra co n tain in g two
d is tin c t o n e -p ro to n olefinic m ultiplets a t 5.63 ppm a n d 5.81 ppm . This is
c o n siste n t w ith th e non-sym m etrical d isp o sitio n of th e a lk e n e .
61
P
T sP
250° C
P
+
CD'
P
13
19. 31
F ig u re 43. P re p a ra tio n of cis - 8 -oxabicyclo [4.3.01 n o n - 2 -e n e .
In th e s y n th e s is of [1 5 ], p h th a lic a n h y d rid e was re d u c e d w ith LAH in
THF to th e c o rre sp o n d in g diol w hich was s u b se q u e n tly rin g -c lo s e d w ith T sC l
in p y rid in e to p h th a la n .
T he B irc h re d u c tio n of p h th a la n clean ly yield ed
- 1 ,6 - - 3 , 4 -8 -o x ab icy clo [4.3 .O jn o n d ien e, [2 6 ]. When [ 26] was h y d ro g e n a te d ,
w ith 10% P t / C c a ta ly s t fo r 5 m inutes a t one atm osphere of h y d ro g e n , only
two p ro d u c ts re s u lte d , 8- c is - o x ab icy clo [ 4 . 3 . Olnonane [12] a n d / \ - l , 6 - 8 o xabicyclo[ 4 .3 .0 ] nonene [1 5 ], in a 5 to I ra tio , re s p e c tiv e ly (F ig u re 4 4 ).
Note th a t [1] was n o t form ed in th e re d u c tio n .
O lefin, [15] was ag ain
collected b y p re p a ra tiv e GLC, (13% DEGS IOnX 1 /4 ') , an d c h a ra c te riz e d b y
xHNMR.
H ere, th e re was a n e x p e c te d ab se n c e of v in y l p ro to n s in th e
s p e c tru m .
P
12
F ig u re
44.
15
S y n th e sis o f /\- l,6 - 8 - o x a b ic y c lo [ 4 .3 .0 ]n o n en e.
62
T heodore had p re v io u sly s y n th e siz e d [1 6 ]. T his com pound was isolated
from th e reactio n m ixture an d c h a ra c te riz e d b y com paring its 1HNMR to
th a t
of
th e
a u th e n tic
sam ple.
T he
only
d a ta
o b tain ed
o x a b ic y c lo [4 .3 .0 ]n o n -l-e n e ,
[1 4 ], was its mass s p e c tru m ,
frag m en tatio n
re te n tio n
p a tte r n
an d
time c o n siste n t
on
cis-8 -
which had a
w ith th a t of th e
com pound.
The id e n titie s of th e p eak s in th e reactio n m ix tu re a t th re e m inutes
an d upon complete re d u c tio n w ere th e re fo re determ ined an d a re illu s tra te d
in F ig u re 45.
CO
CD
CD
OD
12
CD
CD12
(b )
_
F ig u re
45.
a
•
-
^
R eaction composition of th e h y d ro g e n a tio n (P d /C ) of cisbicylco [4 .3 .0 ] non - 3 -e n e a t 3 m inutes (a) an d 15 m inutes ( b ) .
63
T he mechanism s of olefin h y d ro g e n a tio n s a re complex a n d many d etails
a re still u n know n, how ever,, a mechanism p ro p o sed lo n g ago b y H oriuti and
Polanyieo (F ig u re 46) s till p ro v id e s a n a c c u ra te w ay of a c c o u n tin g fo r all
a sp e c ts of olefin h y d ro g e n a tio n of in te r e s t to th e o rg a n ic chem ist.
In s te p ( I ) , h y d ro g e n is d isa sso c ia te ly a b so rb e d on tw o c a ta ly st s ite s
(in d ica te d b y a s t e r i s k ) .
T h ese s ite s n eed no t b e on d iffe re n t ato m s. T he
olefin is th e n (!!absorbed onto two a d jac e n t site s as show n in s te p (2 ).
In
s te p (3 ) , a h y d ro g e n atom ad d s to one carb o n le av in g a m onoabsorbed
sp ecies a n d s u b s e q u e n t ad d itio n of a second h y d ro g e n atom form s th e
re d u c e d alkane w hich is d e ab so rb e d from th e c a ta ly st (s te p 5 ).
Olefin
m igration will o c cu r if th e m onabsorbed sp ecies r e tu r n s to a d ia b so rd ed .
sp ecies d iffe re n t th a n th e o rig in al a s show n in s te p (4 ) , followed b y
d e ab so rb tid n (s te p (2) in r e v e r s e ) . All s te p s e x ce p t th e la s t a re th o u g h t to
be re v e rs ib le .
(1 )
H2
+
2»
J
l-
H
+
H
»
(2 )
-(C H 2-C H =C H -C H 2) -
+
2»
-*
"
*
-(C H 2-C H -C H -C H 2) -
#
(3 )
-(C H 2-C H -C H -C H 2) I
*
(4 )
+
H
I
-=
-
I
.*
*
»
-(C H 2-C H -C H 2-C H 2) -
2»
*
-(C H =C H -C H 2-C H 2) -
-(CH2-CH-CH2-CH2)-
+
1
+
H
I
»
*
(5 )
-(C H 2-C H -C H 2-C H 2) I
»
+
H
I
»
F ig u re 46. P o lan y i's h y d ro g e n a tio n m echanism .
-(C H 2-C H 2-C H 2-C H 2) -
+
2»
64
B ecause olefin m igration d u rin g cata ly tic h y d ro g e n a tio n is co n sid ered
to b e an equilibrium p r o c e s s , c a lc u la tio n ^ a p p ro a ch e s w ere employed to
in v e stig a te th e therm odynam ic sta b ilitie s of olefins [1 ], [1 3 ], [1 4 ], an d [1 5 ].
Table 21 lis ts th e MM2 g e n e ra te d s te ric e n erg ies (ES) a n d olefinic s tra in
e n e rg ie s (O S ).
T he OS is th e e n e rg y d ifferen c e betw een th e olefin an d th e
p a re n t h y d ro c a rb o n b o th in th e ir most sta b le co n fo rm atio n s. All reaso n ab le
conform ations fo r each compound w ere exam ined, an d th e most sta b le
conform ations a re re p o rte d .
T h ese e n e rg ie s a re b eliev ed to b e th o se of th e
global minima how ever th e r e is no rig o ro u s w ay to d em o n strate th is b e lie f.
Table 21.
MM2 C alculated E nerg ies (K cal/m ole)
Olefin
ES
OS
I
10.14
1.99
13
7.02
-1.13
14
6.94
-1.21
15
5.04
-3.11
: H y drocarbon
12
8.15
R ecen tly S c h le y er61-62, e t. a l . , h a s defined a class of " h y p e rsta b le
o lefin s",
medium sized polycyclic r in g system s w ith b rid g e h e a d double
bon d s th a t h av e n e g a tiv e OS e n e rg ie s .
h y d ro g e n a tio n .
T hese olefins h a v e low h e a ts of
Some, h a v in g OS e n e rg ie s le ss th a n ap p ro x im ately -13
K cal/m ole, a re com pletely r e s is ta n t to h y d ro g e n a tio n . 63-6 4 -65 T his re d u c e d
therm odynam ic d riv in g fo rc e , " h y p e r s ta b ility " , h as b e en u s e d to ex p lain th e
65
d ifficu lties in h y d ro g e n a tin g th e se com pounds. In a d d itio n ,
th e s te ric
h in d ra n c e in h ib itin g th e a p p ro a ch of s u b s titu te d olefins to th e c a ta ly st
s u rfa c e h a s also b e e n u s e d to acco u n t fo r th e d ifficu lties in h y d ro g e n a tin g
th e se o le fin s. 66>67
R e p re se n ta tiv e exam ples of th e se o lefin s, re s is tin g
h y d ro g e n a tio n a n d e x h ib itin g la rg e h y p e rs ta b ilitie s , h a v e re c e n tly b e en
re p o rte d b y S ch ley er a n d o th e rs 68, a n d some re p re s e n ta tiv e com pounds a re
illu s tra te d in F ig u re 47.
F ig u re 47.
H y p e rsta b le o lefins.
Note th a t olefins [1 3 ],
[1 4 ], a n d [15] hav e n e g a tiv e OS en erg ies
(T able 21) a n d th e re fo re also e x h ib it
in c re a s in g
" h y p e rs ta b ility " , a
therm odynam ic d riv in g fo rce prom oting b o n d isom erization.
F u r th e r exam ination of th e se olefins b y th e MNDO m ethod, ag ain ,
re v e a ls a la rg e therm odynam ic d riv in g fo rc e prom oting b o n d isom erization
(T able 22).
T he geom etries of th e se olefins w ere optim ized a t th e SCF
level b y minimizing th e h e a ts of form ations w ith th e D av id o n -F le tc h erPowel (DFP) algorithm .
T he initial, geom etries u s e d in th e s e calculations
w ere th o se of th e global minima as d eterm in ed b y MM2 calcu latio n s.
66
T able 22. MNDO calcu lated h e a ts of form ation ( Kcal/m ole)
Olefin
Hr
I-
-42.90
13
-44.47
14
-47.36
15
-50.43
To f u r th e r s tu d y th e olefins in v o lv ed in th is iso m erizatio n , HOMO
71-
bond o rd e rs w ere calculated (T able 23) an d HOMO c o n to u r p lo ts w ere
exam ined (F ig u re 48) b y th e MNDO m ethod.
From a n exam ination of th e
HOMO n -b o n d o rd e rs of th e se com pounds, it is c lea r th a t as th e double
m ig rate s, th e e le c tro n d e n sitie s on th e c arb o n s c o n s titu tin g th e double
b o n d s a re d e c re a sin g .
T h e re is a 20% d e c re a se in th e HOMO n -b o n d o rd e rs
betw een olefins [1] a n d [15]! The m olecular o rb ita l a re e x h ib itin g in c re a s in g
e lec tro n delocalization, ie . h y p e rc o n ju g a tio n .
Table 23.
HOMO P zs atomic o rb ita l co efficien ts of olefinic c arb o n sa n d
HOMO Ti b o n d o rd e rs .
Olefin
. C2 rf
HOMO TtBO
I
.65062
.65060
.8466
13
.64978
.64484
.8380
14
-.61811,
-.62237
.7694
15
-.58179
-.58200
.6772
67
I
13
F ig u re 48. HOMO c o n to u r p lo ts of olefins [1 ], [1 3 ], [1 4 ], an d [15].
From th e
calculational a p p ro a ch e s u sed to in v e stig a te th is simple
sy stem , th e re c lea rly seems to be a s tr o n g therm odynam ic d riv in g fo rce
fa v o rin g bond isom erization.
T his therm odynam ic d riv in g fo rce has been
calculated b y two in d e p e n d e n t m eth o d s, MM2 an d MNDO.
68
In a d d itio n , a n d p e rh a p s more im p o rtan tly , in th is sy stem th e re also
a p p e a rs to b e a s tr o n g co rre la tio n b etw een in c re a s in g " h y p e rsta b lility " an d
d e c re a sin g HOMO Tt-bond o rd e r d e n sity ; a s th e h y p e rs ta b ility in c re a se s th e
HOMO n -b o n d o rd e r d e c re a se s .
T his lead s u s to q u e stio n , does sig n ific a n t
e lec tro n delocalization, a s m easu red b y HOMO n -b o n d o r d e r s , also e x it in
some of th e polycyclic rin g s
sy stem s e x h ib itin g g re a t h y p e rs ta b ility ?
S ch ley er re c e n tly h a s s ta te d , " Em pirical fo rce field calcu latio n s a re th e
only
com putational
m ethods
w hich
allow
to ta l
optim ization
of
all
conform ational isom ers of la rg e molecules while consum ing m odest am ounts
of com puter tim e " .60
T h e re fo re , th e se la rg e , conform ationally flex ib le,
h y p e rs ta b le olefins h av e n o t as y e t b e e n exam ined b y MO calculations an d
th is q u e stio n rem ains u n a n sw e re d .
If delocalization e x ists in th e HOMOs of th e se o lefin s, p e rh a p s th is
h y p e rc o n ju g atio n
is
re s p o n sib le ,
in
ad d itio n
to
th e ir
h y p e rs ta b ilitie s
(therm odynam ic sta b ilitie s) an d s te ric h in d ra n c e s , fo r th e d ifficu lties in th e
h y d ro g e n a tin g
th e s e
com pounds.
As
ex p erim en tal
s u p p o rt
fo r
th is
c o n je c tu re , re call th a t th e re la tiv e s ta b ility of [15] o v e r [1] seem ed to b e
o b se rv e d
in
th e
h y d ro g e n a tio n
of
[26]
w hich
therm odynam ically sta b le (a n d h y p e r s ta b le ) , [1 5 ].
y ield
only
th e
more
T his h y p e rs ta b le olefin
was n o t o b s e rv e d to isom erize an d h a s a HOMO e x h ib itin g sig n ific a n t
e lec tro n
delocalization.
P e rh a p s
th is
delocalization is ,
m olecular o rb ita l b a se s fo r th e co n cep t of h y p e rs ta b ility .
in p a r t,
a
69
An Exam ination of th e Mass S pectrum of
cis-8-oxabicy clo [ 4 . 3 . 01non-3-ene
Mass sp ec tro sc o p y was w idely a c c e ssed to aid in th e c h a ra c te riz a tio n
of th e v a rio u s com pounds a p p e a rin g in th is th e s is . B ecause com pounds [ I ]
an d [7] w ere th e " p a re n t" com pounds of th e se in v e stig a tio n s (com pounds
from w hich all o th e rs w ere d e r iv e d ) , th e ir mass s p e c tra w ere ro u tin e ly
a c q u ire d an d exam ined.
The mass s p e c tra of [1] and [7] a re shown below
in F ig u re s 49 an d 50.
15 26
F ig u re 49.
70 eV EI mass sp ectru m of c is - 8 - oxabicycol[ 4 3 .0 ]n o n -3 -e n e ,
[I].
70
F ig u re 50.
70 eV EI mass sp ectru m of 8 -o x a tric y c lo [4 .3 .3 .0 ]u n d e c -3 e n e , [7 ].
Note th a t in th e sp ectru m of each com pound, a loss of w ater is
o b se rv e d .
It is obvious as to w here th e oxygen o rig in a te s in th is lo ss;
th e re is only one oxygen in each com pound.
B ut w here do th e h y d ro g e n s
orig in ate?
A ssum ing a sim ilar mechanism a cc o u n ts fo r th e loss of w a ter in each
com pound, one could ru le o u t th e rin g - ju n c tu re p r o to n s .
not e x ist in [7 ].
T h ese p ro to n s do
T h e n , b y th e p ro c e ss of elim ination, th e re a re only th re e
rem aining p ro to n p o sitio n s in [ I ] .
E quivalent p ro to n s e x is t a t C2-C 5 , a t
C7-C 0 , an d a t th e v in y l p o sitio n s.
To a d d re s s th e q u e stio n as to w here th e p ro to n s o rig in a te in th e loss
of w a te r, a se rie s of deu teriu m labelled analogues of [1] w ere p r e p a r e d . In
th is s e r ie s , th e C2-C
S
...
,
. . .
p o sitions w ere d eu teriu m labeled to form [4 2 ], th e
C7-C s po sitio n s w ere deuterium labelled to form [4 3 ], a n d b o th th e se
71
positio n s w ere labelled to form [4 4 ].
below (F ig u re 51).
T hese com pounds a re illu s tra te d
From an exam ination of th e mass s p e c tra of th e se
com pounds, it was h o p ed th a t th e major ions in th e sp e c tru m of [1]
(m /z
= 93, 79, an d 69) could be id e n tifie d in ad d itio n to th e q u e stio n as to th e
loss of w a ter.
F ig u re 51.
D2
°2
44
43 .
42
D euterium labeled analogues of c is-8 -o x a b ic y c lo [4 .3 .0 1non-3ene, [ I ] .
In th e s y n th e s is of [4 2 ], cis -te tra h y d ro p h th a lic a n h y d r id e , [1 6 ], was
re d u c e d w ith LAD in T H F.
T he r e s u ltin g d eu teriu m lab elled diol was th e n
rin g -c lo se d w ith T sC l in p y rid in e (F ig u re 52).
0
16
F ig u re 52.
n
0
S y n th e sis of c is - 7 ,7 ,9 ,9 -te tra d e u te ro -8 o xabicyclo[4 .3 .0 ] n o n -3 -e n e ,. [4 2 ].
72
In th e s y n th e s e s of [43] an d [4 4 ], b u ta d ie n e su lfo n e was d isso lv ed in
deu teriu m oxide to w hich was ad d ed a c ata ly tic am ount of m etal sodium .
A fte r s tir r i n g
th is
solution fo r 48 h r s
a t room te m p e ra tu re ,
1HNMR
in d ic a ted th a t d eu teriu m e x ch an g e h a d o c c u rre d in h ig h y ie ld (>95%).
T he
deuterium labelled b u ta d ie n e su lfo n e, [4 6 ], was th e n re flu x e d w ith maleic
a n h y d rid e in xy len e to y ield th e D iels-A ld er p ro d u c t, [4 7 ].
R eduction of
[47] w ith LAH in THF followed b y rin g -c lo s u re w ith T sC l in p y rid in e
r e s u lts in
[4 3 ].
Sim ilarly, re d u c tio n of [47] w ith LAD in THF followed b y
rin g -c lo s u re w ith T sC l in p y rid in e re s u lts in [4 4 ]. F ig u re 53 o u tlin es th e se
s y n th e s e s .
'0
F ig u re 53.
The
S y n th e se s of c is - 2 , 2 , 5 , 5 -te tra d e u te ro -8 -o x a b ic v c lo [4 .3 .0 ]n o n -3 -e n e , [43] a n d c js - 2 , 2 , 5 , 5 , 7 , 7 , 9 . 9 -o c ta d e u te ro 8 -oxabicylo[ 4 .3 .0 ] n o n -3- e n e , [4 4 ].
e le c tro n im pact
(E I)
m ass
illu s tra te d below in F ig u re s 54-56.
s p e c tra
of th e se
com pounds a re
73
F ig u re 54.
70 eV EI mass sp ectru m of c is - 7 , 7 , 9 , 9 -te tra d e u te ro -8 o x a b ic y c lo [4 .3 .0 ]n o n -3 -e n e , [42].
F igure 55.
70 eV EI Mass Spectrum of c is - 2 ,2 ,5 15 -te tr a d e u te r o - 8oxabicyclo [4 .3 .0 ] non - 3- e n e , [43 ].
74
F ig u re 56.
70 eV EI Mass S pectrum of cis_-2, 2 , 5 , 5 , 7 , 7 , 9 , 9 -o c ta d e u te ro 8 -o x ab icy lo [4 .3 .0 ]n o n -3 -e n e , [44].
From an exam ination of th e se s p e c tr a , it a p p e a rs th a t th e re is a loss
of 18, (H 2O ), in [1] an d a loss of 20 (D 2O) in [4 4 ].
While in [42], th e re
a p p e a rs to be th e loss of 18 (H 2O) an d 19 (HDO) an d in [43] th e re a p p e a rs
to th e loss of 19 (HDO) an d 20 (D 2O ) .
T h ese d a ta s u g g e s t th a t th e loss of w ater re s u lts from a t le ast two
d iffe re n t p ro c e s s e s .
In th e loss of 18 from [4 2 ], th e two p ro to n s a p p e a r to
o rig in ate from th e C2-C 5 p o sitio n .
While in th e loss of 19 from [4 2 ], a
p ro to n a p p e a rs to o rig in a te from th e C2-C 5 position a n d a d euterium atom
a p p e a rs to o rig in a te from th e C7-C a p o sitio n . Sim ilarly, in th e loss of 20
from [43] two deu teriu m atoms a p p e a r to o rig in ate from th e C2-C 5 p o sitio n .
While in th e loss of 19 from [4 3 ], a d eu teriu m atom a p p e a rs to o rig in ate
from th e C2-C 5 p o sitio n a n d a p ro to n a p p e a rs to o rig in a te from th e C7-C a
p o sitio n .
75
Note th e second loss in [1 ] , [4 2 ], [4 3 ], an d [4 4 ]. In [1] th is loss
re s u lts in a ion m /z = 93, in [42] m /z = 95, in [43] m /z = 96, an d in [44]
m /z = 98.
[4 4 ].
T his is a loss of 31 fo r [1 ] , 33 fo r [4 2 ], 32 fo r [4 3 ], an d 34 fo r
T h ese d a ta s u g g e s t th e lo sses of (HOCH2) , (HOCD2) , (DOCH2) , an d
(DOCD2) , re s p e c tiv e ly , fo r [1 ],
[4 2 ],
[4 3 ], an d [4 4 ].
T he following
m echanism , illu s tra te d on [1 ], a p p e a rs to acco u n t f o r all of th e o b serv ed
lo sses. (F ig u re 57).
H
H
CH2
+
HOCH2
(m/z = 93)
F ig u re 57.
Loss of HOCH2 from cis^S-o x ab icy clo [ 4 .3 .0 ] n o n -3-e n e , [ I ] .
Note th e major io n , m /z = 69, in [1] an d [42]
T h is ion seems to
c o rre sp o n d to th e major io n , m /z = 72 in [43] an d [4 4 ].
T h ese ions a re
th e re s u lt of a loss of 55, 56, 59, an d 60, re s p e c tiv e ly , f o r [1 ] , [4 2 ], [4 3 ],
an d [4 4 ].
T h ese d a ta s u g g e s t th e loss of (CH3-CH=CH-CH2) fo r [1 ],
( CH2D-CH=CH-CH2)
CD3CH=CH-CD2)
fo r
fo r [4 4 ].
[4 2 ],
(CD2H-CH=CH-CD2)
fo r
[4 3 ],
an d
T he follow ing m echanism , a g ain illu s tra te d on
[1 ], seem s to acco u n t fo r all of th e se lo sse s.
(
76
F ig u re 58.
Loss of CH3-C H -C H -C H 2- from c is -8 -o x a b ic y c lo r4 .3 .01non-3ene, [ I ] .
Note th e loss of th e major ion m /z = 79 in [1] a n d in [4 3 ].
th e major ion m /z = 82 in [43] a n d in [4 4 ].
Note also
T h e se ions a re th e re s u lt of a
loss of 45 in [1 ] , 49 in [4 2 ], 46 in [43] a n d 50 in [4 4 ]. T h e se d a ta s u g g e s t
the loss of (CH3-O -C H 2) , (CHD2-O -C D 2) , (CH2D -0 -C H 2 ), an d (CD3-O CD2) , re s p e c tiv e ly , fo r [1 ] , [4 2 ], [4 3 ], a n d [4 4 ]. A m echanism acco u n tin g
fo r all th e s e o b s e rv e d lo sses is illu s tra te d fo r [1] in F ig u re 59.
77
(m/z = 79)
F ig u re 59. Loss of CH3-O -C H 2 from c is - 8 -o x ab icy clo f4 .3 . O ln o n -3 -en e.
[I]'
From th is s tu d y , th e oxygen atom 's role in a nu m b er of frag m en tatio n
p ro c e sse s h av e b e e n s tu d ie d .
T he major ions in th e (E I) m ass sp ectru m of
[1] h av e b een d eterm ined an d m echanism s, illu s tra tin g th e ox y g en atom 's
role in th e frag m en tatio n p ro c e s s e s , h a v e b e en p ro p o se d .
78
CHAPTER 3
CONCLUSIONS
Summary of th e R esearch
We h av e c a rrie d o u t a com prehensive p ro g ram com bining experim ental
an d calculational m ethods to exam ine th e ro le th e o x y g en atom p lay s in
im p artin g
s tr u c tu r e
an d
re a c tiv ity
on a
se rie s
of o x y g en co n tain in g
h e tero cy c le s . T h ese s tu d ie s hav e c le a rly a n d e le g a n tly a d d re s s e d a num ber
of fundam ental q u e stio n s w hich a re sum m arized below.
An
ab se n c e
of
s te re o s e le c tiv ity
electro p h ilic a d d itio n s c o n d u cted on [7 ] .
was
o b se rv e d
in
a
num ber
of
T his was in te r p r e te d to mean th e
oxygen atom does n o t in flu en ce ste re o s e le c tiv ity in th is sy stem .
T h ese
r e s u lts a re c o n siste n t w ith calculation stu d ie s co n d u cted on [7] which
s u g g e s t:
(I)
T he Tt-faces of th e double b o n d a re s te ric a lly eq u iv alen t
(b ecau se th e two a n tic ip a te d b o a t conform ations of [7] a re e n e rg e tic a lly
e q u iv alen t a n d th e re fo re b o th conform ations e x ist in ap p ro x im ate eq u al
equilibrium a b u n d a n c e ).
(2)
T h ese conform ations h a v e HOMOs of equal
e n e rg y a n d th e re fo re sh o u ld h av e id e n tic al re a c tiv itie s .
(3)
T h e re is ho
c o n trib u tio n b y th e ox y g en atom in th e HOMOs of th e s e conform ations
w hich could h av e p o s sib ly d ire c te d th e in itia l electro p h ilic ad d itio n (b a se d
upon h a rd a n d s o ft acid b a se th e o r ie s ) .
T he m odest s te re o s e le c tiv ity o b s e rv e d in a n u m b er of electro p h ilic
a d d itio n s co n d u cted on [1] w ere a ttr ib u te d to th e s te r ic no n eq u iv alen ce of
th e u -fa c e s of th e double b o n d .
T he in itia l electro p h ilic a tta c k a p p e a rs to
79
o c cu r on th e le ss s te ric a lly h in d e re d face a n ti to th e o x y g en atom.
Id en tical re a c tiv itie s an d p ro d u c ts
(a m ix tu re of alk en es an d th e
com pletely in v e rte d alcohol a n d m ethoxy com pounds) w ere o b se rv e d in th e
solvolysis of th e s y n - an d a n ti- to sy la te s of [ I ] .
T h is was in te rp re te d to
mean th e ox y g en atom is not in v o lv ed in in flu en c in g th e re a c tiv ity of
th e se com pounds.
intim ate ion p a ir
A re a ctio n schem e,
(IIP )
in th e r a te
in v o lv in g th e form ation of an
d eterm in in g s te p
of th e re a ctio n
followed b y p a rtitio n in g in to v a rio u s re a ctio n p ath w ay s of elim ination a n d
s u b s titu tio n , was p ro p o se d to d e sc rib e th e se p ro c e ss e s .
A su b tle r a te enhancem ent (1 .5 3 ) was o b se rv e d f o r th e a n ti- to sy la te
d e riv e d from [7] re la tiv e to th e s y n -iso m er.
In a d d itio n to a m ixture of
alk en es an d com pletely in v e rte d alcohol a n d m ethoxy com pounds (fo u n d in
th e sy n -is o m e r), a m ethoxy com pound, a p p a re n tly r e s u ltin g from a 1,2
h y d rid e s h if t, was o b se rv e d in th e p ro d u c t s tu d y of th e a n ti- isom er.
A
re a ctio n schem e, in v o lv in g a h y d ro g e n b o n d ed stab ilized IIP form ed in th e
ra te d eterm in in g s te p of th e re a ctio n followed b y p a rtitio n in g in to re a ctio n
p ath w ay s of elim ination, s u b s titu tio n , a n d a 1,2 h y d rid e s h if t, was p ro p o sed
to ratio n alize th e r a te enhancem en t.
While, a reactio n schem e id en tical to
th a t p ro p o se d in th e bicyclic to sy la te s was u s e d to d e sc rib e th e sy n -to s y la te
of [7 ].
M odest
s te re o s e le c tiv ity
h y d ro g e n a tio n of [35].
(3
:
I)
was
o b se rv e d
in
th e
cataly tic
A lthough th e a b so lu te stereo c h e m istrie s of th e
p ro d u c ts w ere n o t d eterm in ed , as a p re lim in a ry in v e stig a tio n , th is d a ta
seems
to
sug g est
h y d ro g e n a tio n .
an d W ilkening.
an
o x y g e n /c a ta ly s t
in te ra c tio n
d ire c tin g
th e
T his in te ra c tio n was p re v io u s ly su g g e s te d b y O tz e n b e rg e r
80
T he olefins
re s u ltin g from double bond isom erization d u rin g th e
c ataly tic h y d ro g e n a tio n of [1] w ere c h a ra c te riz e d .
An exam ination of th e ir
therm odynam ic s ta b ilitie s , b y th e MM2 a n d MNDO m eth o d s, rev ealed a
therm odynam ic
c o rrelatio n
d riv in g
b etw een
fo rce
th e
p rom oting
h y p e rs ta b ility
th e
(a
bond
m easure
iso m erization.
of
A
therm odynam ic
sta b ility as, d eterm in ed b y MM2 calcu latio n s) of th e se com pounds an d th e ir
HOMO n -b o n d o rd e rs was o b s e rv e d .
As h y p e rs ta b ility in c re a s e d , th e
HOMO n -b o n d o rd e rs d e c re a se d , (th e HOMOs e x p erien c e d more electro n
d elo calizatio n ).
T his e le c tro n delocalization was u s e d , alo n g w ith th e
in c re a se d therm odynam ic s ta b ility an d s te ric h in d ra n c e to ratio n alize th e
d ifficu lty in h y d ro g e n a tin g h y p e rs ta b le o lefin s.
T he major ions in th e BI m ass s p e c tra of [1] w ere d eterm in ed b y an
exam ination of a se rie s of deu teriu m lab elled analogues of [1 ] , w hich w ere
s y n th e s iz e d .
S u g g e sted F u tu re Work
An obvious ex ten sio n of th is w ork would b e to p re p a re th e n itro g e n
an d s u lfu r analogues of [1] an d [7] a n d determ ine th e ro le of th e n itro g en
an d
s u lfu r
atoms
in
in flu en c in g
a d d itio n s to th e se a lk e n e s .
th e to sy la te s
th e
ste re o c h e m istry
of electro p h ilic
In a d d itio n , a n exam ination of th e solvolysis of
d e riv e d from th e se
com pounds would also illum inate th e
n itro g e n an d s u lfu r atoms role in im p a rtin g re a c tiv ity on th e molecule in
th e se r a th e r conform ationally rig id s y s te m s . B ecause th e lone p a ir electro n
o rb itals of th e s e heteroatom s a re more p o larizab le th a n o x y g e n , one would
e x p ec t g r e a te r in flu en c es in. im p a rtin g b o th ste re o c h e m istry a n d re a c tiv ity
on th e molecule th a n was o b se rv e d in th is w ork.
81
It would also be in te re s tin g to exam ine th e role th e o x y g en atom p lay s
in in flu en c in g s tr u c tu r e a n d re a c tiv ity in a more conform ationally flexible
sy stem .
A
sy stem
in
w hich
to
a d d re s s
th is
q u e stio n
is
8 ,1 2 -
b io x a tric y lo [4 .3 .5 .0 ]te tra d e c -3 -e n e a n d th e to sy la te s d e riv e d from th is
a lk en e .
H ere, b e ca u se f a r g r e a te r conform ational fle x ib ility e x ists (as
com pared to [ 7 ] ) , th e o x y g en atom h a s th e p o ssib ility of g e ttin g much
c lo ser to th e
re a c tiv e
s ite .
One m ight th e re fo re p re d ic t a g re a te r
in flu en ce im p arted b y th e oxygen atom .
To f u r th e r exam ine th e role th e o x y g en atom im p a rts on in flu en cin g
S tereo ch em istry in c ata ly tic h y d ro g e n a tio n s,
one sh o u ld s y n th e s is a n d
su b je c t to c ata ly tic h y d ro g e n a tio n 7, ll-d io x a -3 -m e th y ltric y lo [4 .3 . 3 . 0 ]u n d ec-3
e n e.
H ere, one would p re d ic t in c re a se d re a c tiv ity to w ard s h y d ro g e n a tio n
re la tiv e to [3 5 ].
If th is is in d eed th e c ase , ad d itio n al s u p p o rt fo r th e
o x y g e n /c a ta ly s t in te ra c tio n , p ro v id in g a n e n tro p ic ra tio n a l to acco u n t fo r
th e in c re a se d re a c tiv ity of oxygen co n tain in g h e tero cy le s w ould b e g ain ed .
An obvious e x ten sio n to th e w ork c o rre la tin g h y p e rs ta b ility an d n -b o n d
o rd e r would b e to exam ine b y th e MNDO m ethod a n u m b er of S ch ley er’s
h y p e rs ta b le olefins to determ ine if la rg e e lec tro n delocalization e x ists in
th e HOMOs of th e s e o le fin s.
T h is w ould a d d re s s th e q u e stio n re g a rd in g ,
th e u n iv e rs a lity of th e co rrelatio n in v o lv in g h y p e rs ta b ility , a n d HOMO tibond o rd e r.
82
CHAPTER 4 '
EXPERIMENTAL
G eneral P ro c e d u re fo r Solvolysis
A g la ss c o n d u c tiv ity cell was tre a te d w ith p a r a -to lu en esu lfo n ic acid
(th e acid g e n e ra te d u p o n solvo ly sis) fo r 24 h o u rs .
T he acid solution was
th e n rem oved from th e cell an d th e cell o v e n -d rie d .
T h en 25 ml of th e
s ta n d a rd 50% aqu eo u s m ethanol so lu tio n w ere ad d ed to th e cell which was
th e n p laced in a c o n sta n t te m p e ra tu re b a th an d allowed to e q u ilib ra te .
Upon te m p e ra tu re e q u ilib ra tio n , ap p ro x im ately 2 mg of th e s u b s tr a te was
ad d ed
to
th e
cell.
T he
s u b s tr a te
was allowed to d isso lv e a n d th e
te m p e ra tu re e q u ilib ra te (2-4 m in u te s).
Upon e q u ilib ra tio n , th e solvolysis
re a ctio n s w ere followed fo r 3-5 h a lf-liv e s a n d , a f te r 15 h a lf liv e s, an
in fin ity con d u ctan ce value (c„) was m easu red .
T he in fin ity value was
checked to in s u re th a t it was n o t c h a n g in g . ’ If th e in fin ity was c h an g in g
th e
k in e tic
ru n
was
re p e a te d .
T he
con d u ctan ce
and
m easurem ents w ere re c o rd e d w ith a L a b o ra to ry In te rf a c e .
te m p e ra tu re
T h is d ig ital to
analog c o n v e rte r in te rfa c e d th e c o n d u c tiv ity cell an d th e rm is to r to a PC ,
allow ing fo r sim ultaneous acq u isitio n of co n d u ctan ce, te m p e ra tu re , an d time
m easu rem en ts. R ate c o n sta n ts w ere calcu lated b y a le a s t-s q u a re s tre a tm e n t
of In(Cro-Cx) v s time (s e c o n d s ).
w ere o b ta in e d .
C o rrelatio n co efficients g r e a te r th a n 0.9995
A ctivation p a ra m e te rs w ere calcu lated b y le a s t s q u a re s
tre a tm e n t of ln (k ) v s 1 /T (K 0) . C o rrelatio n coefficients g r e a te r th a n 0.9998
w ere o b ta in e d .
All k in e tic ex p erim en ts w ere com pleted u s in g th e same
83
conductance cell.
T he p ro d u c ts of solvolysis fo r each to sy la te w ere com bined an d most
of th e m ethanol was rem oved b y g e n tle column d istilla tio n .
T h e n , th e
re sid u e was e x tra c te d se v e ra l times w ith d ieh lo ro m eth an e, a n d th is solution
was d rie d o v e r MgSO4 .
P ro d u c t a n a ly se s a n d p e ak in te g ra tio n s w ere
o b tained b y GLC e q u ip p ed w ith a DB5 .5 Sm-ID cap illary column an d FID.
P lots of ln (c „ -c x ) v s time (se co n d s) fo r th e 50% aq u eo u s m ethanolysis
fo r each to sy la te a t th re e d iffe re n t te m p e ra tu re s a re illu s tra te d in F ig u res
60-71.
P lots of ln (k ) v s 1 /T (K°~^) fo r each to sy la te a re illu s tra te d in
F ig u res 72-75.
In (C0O- C)
O
id
0.0
F ig u re 60.
1380.0
2760.0
4140.0
5520.0
TIME (Sec.)
Plot of ln (c _ - c , ) vs time (se co n d s) fo r th e 50%
a q u eo u s m ethanolysis of [19] a t 35.84° C . fv = 0 6 0 7 1 4
*
I O--4V
4.
A
O S 1 7 .
D
- I
Ar>AA I
j
’
6900.0
O
In(C0 0 -C)
CO
0.0
Figure 61.
1260.0
2520.0
3780.0
5040.0
Plot of ln(c_ - c„) vs time (seconds) for the 50%
aqueous methanolysis of [19] at 50.00° C. [y = 3 4 7 1 4 4
* 10 x + 5.2682; R = 1.0000].
6300.0
In(C00-C)
300.0
600.0
900.0
1200.0
TIME (Sec.)
Figure 62.
Plot of ln(c_ - Cx ) vs time (seconds) for the 50%
aqueous methanolysis of [19] at 62.87° C. [v = 1 4 Ti4
* 10r+x + 5.9913; R = 1.0000],
1500.0
In(C0 0 -C)
CO
1380.0
2760.0
4140.0
5520.0
TIME (Sec.)
Figure 63.
Plot of ln(c„ - c„) vs time (seconds) for the 50%
aqueous methanolysis of [31] at 35.78° C. [y = 0.60730
* 10 "x + 5.2310; R = 0.9999].
6900.0
In(C0 0 -C )
o
CO
CO
960.0
F ig u re 64.
1920.0
2880.0
3840.0
I IIVic t o e c . /
Plot of ln (c_ - c x ) v s time (se c o n d s) fo r th e 50%
o0l3LSiS 0J J 3H a t 50.20° C. [y = 3.3231
*10-*x + 5.6252; R = 0 .9 9 9 6 ].
4800.0
O
CO
).0
300.0
RS
igure 65.
600.0
900.0
TIME (Sec.)
1200 0
Plot of ln(c_ - c x ) vs time (seconds) for the 50%
aqueous methanolysis of [31] at 63.00° C . [v = 1 3 9 1 9
* 10“ x + 6.2719; R = I.0000].
1500.0
In(C0 0 -C)
o
1380.0
2760.0
4140.0
5520.0
TIME (Sec.)
Figure 6 6 .
Plot of ln(c_ - c„) vs time (seconds) for the 50%
aqueous methanolysis of [ 2 4 ] at 35.82° C . [y = 1.9123
* 10~*x + 4.6321; R = 0.9999].
6900.0
In(Cco-C)
O
480.0
960.0
1440.0
1920.0
TIME (Sec.)
Figure 67.
Plot of ln(c_ - C j t ) vs time (seconds) for the 50%
aqueous methanolysis of [24] at 50.10° C. [y = 9.3501
* IO-11X + 4.9987; R = 0.9998].
2400.0
In(C0 0 -C)
o
.0
120.0
Figure 68.
Plot of ln(c_ - C j t ) vs time (seconds) for the 50%
aqueous methanolysis of [24] at 63.00° C . [y = 37.923
* I Q - 1X + 45.3860; R = 1.0000].
240.0
360.0
480.0
TIME (Sec.)
600.0
In(C0 0 -C)
1380.0
2760.0
4140.0
TIME (Sec.)
F ig u re 69.
5520.0
( seconds)
a q u eo u s m ethanolysis of [32] a t 35.70° C . [y - 1.4270
* 10"*x + 4.9175; R = 0 .9 9 9 9 ].
6900.0
In(C0 0 -C )
O
300.0
F ig u re 70.
600.0
900.0
TIME (Sec.)
1200.0
Plot of In (c_ - Cjt) v s time (s e c o n d s ) fo r th e 50%
a q u eo u s m ethanolysis of [32] a t 50.15° C. [y = 2.9031
* 10"*x + 4.7612; R = 0.9 9 9 9 ].
1500.0
In(C0 0 -C)
30
F ig u re 71.
120.0
240.0
360.0
480.0
Plot of ln (c _ - C
3t) v s time ^(seconds) fo r th e 50%
aqueouB m ethanolysis of [32] a t 62.90° C . [y = 52 731
* 1 0 - x + 5.6532; R = 0 .9 9 9 7 ].
Y
1
600.0
6.0
-
7.0
-
8.0
-
9.0
-
10.0
-
2.95
3.00
3.05
3.10
.
3.15
3.20
V
J xIOd (0K'1)
F ,g u r e 7 2 -
,o r 1191 • ' y = I = H i = X +
6.0
-
7.0
-
8.0
-
9.0
-
10.0
-
VT x 10° (uK'1)
F ig u re 73.
Plot of In(It)
5.0
-
6.0
-
7.0
-
8.0
-
9.0
-
I
2.95
I
I
I
3.00
3.05
3.10
I
Q 3.15
I
I—
3.20
3.25
VT x IOd (0K'1)
F igure 74.
Plot of ln (k ) v s 1 /T (K -1 ) fo r [2 4 ]. [y = 11446.82x +
28.470; R = 1.0000].
3.30
5.0
-
6.0
-
7.0
-
8.0
-
9.0
-
2.95
3.00
3.05
3.10
Q 3.15
3.20
1/T x IOd (0K"1)
F ig u re 75.
Plot of ln (k ) v s 1 /T (K -1 ) fo r [3 2 ]. [y = 11077.5x +
100
R ep o rted b o ilin g an d m elting p o in ts a re u n c o rre c te d .
p ro to n
NMR s p e c tra
w ere re c o rd e d
on a
250 MHz sp ec tro p h o to m ete r
e q u ip p ed w ith a n ASPECT 2000 d a ta p ro c e s s in g sy ste m .
!obtained u s in g deuterochlorofo rm a s
re p o rte d in ppm re la tiv e to TMS.
C arbon an d
so lv en t an d
S p e c tra w ere
chemical s h ifts w ere
E lectron im pact (E I) an aly ses w ere
co n d u cted on a VG MMl 6 m ass sp e c tro m e te r in te rfa c e d w ith a V arian Model
3700 gas
ch ro m ato g rap h
e q u ip p ed
w ith
a
SOmDB-I
c ap illary
column.
A ccu rate m ass a n d chemical ionization (C l) mass s p e c tra l m easurem ents w ere
com pleted on a VG 707OE m ass sp e c tro m e te r.
X -ra y c ry sta llo g ra p h ic d a ta
w ere ob tain ed w ith a N icolet R3mE d iffra cto m e te r an d p ro c e ss e d b y d ire c t
m ethods u s in g Solve o r R a n t.
FT -IR sp e c tro m e te r.
IR d a ta w ere o b tain ed u s in g a Nicolet DX
Sem i-em pirical m olecular o rb ita l calculations w ere
com pleted b y th e MNDO m ethod a n d fo rce field calcu latio n s b y th e MM2
m ethod.
T h ese calculations w ere p refo rm ed u s in g th e TRIBL p ro g ram
re s id in g on a VAX-8550 com pu ter.
A n h y d ro u s TH F, d ie th y l e th e r , a n d
hexane w ere o b tain ed b y distillatio n from b enzophenone k e ty l.
amine
an d
p y rid in e
dichlorom ethane
was
w ere
d istilled
d istille d
from
from
P 2Os .
calcium
F lash
D iisopropyl
h y d rid e
and
sep a ra tio n s
w ere
com pleted u s in g a 500 ml fla sh column p a ck e d w ith 40 pm diam eter silica
gel an d e q u ip p ed w ith a UV a b so rb a n c e m onitor.
A so lv en t system of
dichlorom ethane : h e x an e : e th y l a c e ta te in th e re la tiv e ra tio 20 : I : I
was u s e d in all s e p a ra tio n s .
B aseline re so lu tio n s w ere o b ta in e d only w hen
th e column was sp o tte d w ith le ss th a n 200 mg of p ro d u c t.
101
P re p a ra tio n of ( c is ) - 8 -o x ab icy clo f 4 .3 .0 1n o n -3 - e n e , F l l .
A solution of c is - 1 , 2 , 3 , 6 -te tra h y d ro p h th a lic a n h y d rid e (4 0 .0 g , 0.264
moles) in 150 ml of d r y THF was a d d e d to a s tir r in g solution of LAH
(1 1 .0 g , 0.240 moles) in 100 ml of d r y T H F.
A fte r a d d itio n was com pleted
th e g ra y m ix tu re was s tir r e d fo r 12 h r s . a t room te m p e ra tu re .
T he re a ctio n
was th e n cooled to 0°C a n d h y d ro ly z e d b y dropw ise ad d itio n of 100 ml of
w et e th e r .
T he re s u ltin g w hite s a lts w ere su ctio n filte re d off an d th e
so lv en t rem oved b y r o ta r y e v ap o ratio n to y ield 22.4 g of th e c le a r diol (60%
y ie ld ) .
T he diol was th e n ta k e n u p in 200 ml of d r y p y rid in e a n d s tir r e d ,
u n d e r a rg o n a t a g en tle re flu x , while a solution of T sC l (3 3 .4 g , 0.125
moles) in p y rid in e was ad d ed d ro p w ise.
A fte r th e a d d itio n was com pleted,
th e m ix tu re was s tir r e d a t re flu x fo r a n ad d itio n al 12 h r s .
T he re s u ltin g
d a rk e n e d solution was th e n p o u re d o v e r a c o n c e n tra te d s u lfu ric acid on
1
c ru s h e d ic e.
T he re s u ltin g acidic so lu tio n was e x tra c te d th r e e times w ith
dichlorom ethane.
T he e x tra c ts w ere com bined an d w ashed w ith s a tu r a te d
sodium b ic a rb o n a te solution followed b y a n aq u eo u s w a sh .
A fte r d ry in g
o v e r Mg(SO4) 2 a n d th e rem oval of so lv en t b y r o ta r y e v a p o ra tio n , th e
re s u ltin g c le a r liq u id was d istilled to y ie ld 16.0 g (0.129 moles) of a c lea r
liq u id (80 % y ie ld ).
BP2 . 3 = .45-48°C
IR:
lite ra tu re BPi a = 90-93oC
3024, 2968, 2925, 2843, 1088, 1055, 468, 462 cm"1
1HNMR:
1.90 (2 H ), 2.15 (m ethylene en v elo p e, 4H ), 3.51 ( q , 2H ),
3.85 ( q , 2H ), 5.65 ( t , 2H ).
13C NMR:
MS (E l):
23.80 (2 C ), 34.97 (2 C ), 72.80 (2 C ), 125.58 (2 C ).
M+ = 124, 106, 93, 79 (b a s e ), 69, 54, 39, 27.
102
MS (C l):
MH+ = 125 (b a s e ), 107 .
'
a n aly sis - HRMS calcu lated fo r CaH12O = 124.18424; fo u n d = 124.08879.
P re p a ra tio n of ( c i s ) - l , 6 -d icarb o m eth o x y b icv clo l4.3.01 -n o n -3 -e n e . (181.
A solution of 250 ml of d r y TH F, 203 ml of 2.6 M n -B u L i (0.528 moles)
a n d 75.0 ml of diisopropylam ine (0.528 moles) was s tir r e d u n d e r a rg o n a t78°C
fo r
15
m in u te s.
T h en
41.7
g
(0.211
dicarbom ethoxycyclohexene was addled d ro p w ise,
so lu tio n .
moles)
of
c is -3 ,4 -
c re a tin g a b r ig h t re d
A fte r a d d itio n was com pleted, th e solution was allow ed to s t i r fo r
15 m in u tes. T he solution was th e n w arm ed to -IO0C a n d 25.0 ml (0.230
moles) of 1 , 3-dibrom opropane w ere a d d e d d ro p w ise, s lig h tly lig h te n in g th e
b r ig h t r e d so lu tio n .
T he solution was allowed to warm to room te m p e ra tu re
a n d s tir r e d fo r 2.5 h r s .
T he so lu tio n was th e n n e u tra liz e d w ith a d ilu te
HCl solu tio n . T he re s u ltin g p h a se s w ere s e p a ra te d a n d th e aq u eo u s la y e r
e x tra c te d th r e e tim es w ith diclorom ethane.
T he com bined e x tra c ts w ere
d rie d a n d th e so lv en t rem oved b y r o ta r y e v ap o ratio n . T h e re s u ltin g lig h t
yellow liq u id was d istille d to yield 25.6 g (0.108 moles) of a c le a r v isco u s
liq u id (52% y ie ld ).
BP1 . s = 104-111°C
IR:
2900, 1730, 1690, 1140, 1320, 1280, 1205, 1176, 735 cm"1 .
1H NMR:
5.64 ( t , 2H ), 2.65 (m, 4H ), 2.50 (d d d , 2H ), 2.21 (m, 2H ), 2.19
(d d d , 2H ).
MS (E l): 207 (-O M e), 206, 178, 163, 152, 119 ( b a s e ) , 105, 91.
P re p a ra tio n of S -o x a tric y c lo !4 .3 .3 .0 1 u n d e c-3 -en e , [7 ].
A solution of 16.0 g of [18] (0.067 moles) in 40 ml of d r y THF was
ad d ed dropw ise a t 0°C to a s tir r i n g so lu tio n of 3.60 g of LAH (0.095
moles) in 350 ml of d r y T H F.
T he re a c tio n was s tir r e d o v e rn ig h t an d th e n
h y d ro ly z e d w ith w et e th e r .
The w hite lithium s a lts w ere filte re d off a n d
th e so lv en t rem oved b y r o ta r y ev ap o ratio n to y ield 9.14 g (0.053 moles) of
th e diol, a w hite solid.
. .
T he diol was d isso lv ed in 200 ml of d r y p y rid in e an d b ro u g h t to re flu x
u n d e r a rg o n .
T h en 1 1 .7 g of T sC l (0.062 moles) in 50 ml of p y rid in e w ere
ad d ed dropw ise to th e s tir r i n g so lu tio n .
o v e rn ig h t.
T he re a ctio n was s tir r e d a t re flu x
T he d a rk e n e d solution was th e n
H2SO4 on ice to a c id ify .
p o u re d o v e r c o n c e n tra te d
E x trac tio n w ith diclorom ethane y ield a c lea r
liq u id , w ith a cam phor-like fra g ra n c e , w hich was d istille d re s u ltin g in 7.38
g (0.045 moles) of th e d e sire d p ro d u c t (88% y ie ld ).
BP1 . o = 50-53°C
1H NMR: 5.86 ( t , 2H ), 3.57 ( s , 4H ), 2.03 ( s , 4H ), 1.60 (m ethylene en v elo p e,
6H ),
13C NMR:
128.5 ( d ) , 81.4 ( t ) , 55.1 ( s ) , 40.0 ( t ) , 32.5 ( t ) , 24.1 ( t ) .
MS (E l):
M+ = 164, 146, 133, 119, 105, 91 ( b a s e ) , 79, 77.
MS. (C l) :
MH+ = 165 ( b a s e ), 147, 135, 119, 109
A nalysis - HRMS: calcu lated fo r C11H16O = 164.1197, fo u n d = 164.1190
H ydro b o ratio n of (c is)-8 -o x a b ic v c lo [4 .3 .0 1 n o n -3 -e n e , [11.
T he a lk e n e , [1 ] , (6 .3 0 g , 0.044 moles) in 40 ml of d r y THE was ad d ed
to 1.68 g (0.044 moles) of NaBH4 .
A .n itro g e n atm o sp h ere was c re a te d an d
th e solution was cooled to 0°C. T h en 10.9 ml (0.088 moles) of BF3O (C 2Hs )
w ere ad d ed dropw ise to th e s tir r in g so lu tio n . A fte r I h r . , th e re a ctio n was
q u e n ch e d w ith a small am ount of w a te r followed b y th e slow a d d itio n of. 25
ml of 3N NaOH a n d 25 ml of 30% H2O2 .
A fte r th e ad d itio n was com plete,
th e solution was s tir r e d fo r 30 m in u tes.
T he solution was th e n e x tra c te d
w ith dichlorom ethane;- th e e x tra c ts w ere d rie d arid th e so lv e n t rem oved b y
104
r o ta r y e v ap o ratio n to a ffo rd th e c le a r liq u id w hich was d istilled to yield
4.81 g (0.034 moles) of th e alcohol m ix tu re .
GLC an aly sis show ed th a t th e
s y n - an d a n ti- alcohols w ere p r e s e n t in a 9 : I ra tio , re s p e c tiv e ly (75%
y ie ld ) .
B P .s = 90-92°C (m ix tu re)
sy n -B icy clic alcohol, [51.
IR :
3320, 2930, 2880, 1450, 1127, 1072, 1025, 987, 888 cm"1 .
1HNMR : 1 .4 5 -1 .2 0 (m ethylene en v elo p e, 2 H ), 1 .5 8 -1 .9 0 (m , 5H ), 2.10 -2 .3 5
(m, 2 H ), 3 .5 2 -3 .6 8 (m 3H ), 3 .7 4 -3 .8 4 (m , 2H ).
MS (E l): 124 (-H 2O ), 109, 95, 82, 79, 69 (b a s e ), 55, 43, 41.
MS (C l) : MH+ = 143, 125, 109
a n aly sis - HRMS calcu lated fo r Cs H12O2 = 142.1996; Found = 142.0979.
an ti-B icy clic alcohol, [6 ].
IR ;
3320, 2930, 2880, 1450, 1150, 1127, 970 cm"1 .
1H NMR: 1 .5 8 -1 1 15 (m ethylene envelope 4H ), 1 .8 5 -1 .6 5 (m , 3H ), 2.15 -2 .0 5
(m, 1H ), 2 .50-2.35 (M, 1H ), 3 .5 8 -3 .4 5 (m, 2H ), 3 .8 3 -3 .6 8 (m, 3H ).
MS (E l):
124 (-H 2O ), 114, 109, 95, 83, 79 (b a s e ), 68, 55, 43, 41.
MS (,C l):
MH+ = .143, 125, 107.
a n aly sis - HRMS calcu lated fo r Cs H12O2 = 142.1996; Found = 142.0949.
E poxidation of (c is)-8 -o x a b ic v clo F 4 .3 .0 1 n o n -3 -e n e , [11.
T he a lk e n e ,
[1 ] ,
(500 mg, 4.00 moles) was d isso lv ed in 15 ml of
chloroform to w hich was ad d ed 760 mg (4 .4 0 moles) of mCPBA.
solution was s tir r e d u n d e r a rg o n a t room te m p e ra tu re o v e rn ig h t.
The
T hen 10
ml of 10% NaS2O3 was ad d ed along w ith 10 ml of w a te r a n d 20 ml of
d ich lorom ethane.
T he
o rg an ic la y e r was
collected, a n d
w ashed w ith
s a tu r a te d NaHCO3 an d w a te r, d rie d o v e r MgSO4 , a n d th e so lv en t rem oved
105
b y r o ta r y e v ap o ratio n to yield 500 mg of a c lea r liq u id (80% y ie ld ).
GLC
(13% DECS, lO 'x l/4 " , 120°C) show ed th e s y n - an d a n ti- ep o x id es of [1] in
th e ra tio 1 : 4 ,
re s p e c tiv e ly .
To determ ine th e re la tiv e ste re o c h e m istry of th e two isom ers, th e
major epoxide was cleanly collected b y GLC.
T his ep o x id e was th e n
combined w ith 10 ml of d r y THF to w hich was ad d ed a "p in ch " of LAH.
T he solu tio n was allowed to s t i r u n d e r a rg o n o v e rn ig h t.
A small am ount of
w et e th e r was a d d e d to q u e n ch th e re a c tio n , th e s a lts w ere filte re d off an d
th e so lv en ts rem oved b y r o ta r y ev ap o ratio n to y ield a c le a r liq u id .
T he
GC/MS a n d 1H NMR of th is compound w ere id e n tic al to th a t of th e a n tialcohol, th u s d e term in in g th e re la tiv e ste re o c h e m istry of th e major epoxide
to b e th e a n ti-isom er.
In a sim ilar fa sh io n th e m inor epoxide was re d u c e d
y ie ld in g only th e s y n -alcohol.
sy n -b ic y lic e p o x id e , [2 0 ].
1H NMR: 2 .2 7 -1 .8 2 (m ethylene en v elo p e, 6H ), 3.18 ( s , 2H ), 3 .6 1 -3 .5 5 (d d d ,
2H ), 3.9 2 -3 .8 1 (d d d , 2H ).
MS (E l):
M+ = 140, 122, 92, 79 ( b a s e ) , 69, 53, 41.
a n ti-b ic y lic ep o x id e, [211.
1HNMR: 1.8 9 -1 .8 1 (d d , 2H ), 2 .1 5 -2 .0 5 (m, 2H ), 3.12 ( s , 2H ), 3 .2 5 -3 .2 0 (d d d ,
2H) 3 .9 4 -3 .8 8 (d d d , 2H ).
MS (E I)
M+ = 140, H O, 96, 81, 69 ( b a s e ) , 53, 41.
Q x y m e rc u ratio n /d em ercu ratio n of c is -8 -oxabicyclo 1 4 .3 .0 ]n o n -3- e n e , FH .
T he alkene (7 .0 0 g , 0.056 moles) w as d isso lv ed in 40 ml of a 50:50TH F:H2O solution a n d a d d e d to 20.0 g of m ercu ric a c e ta te (0.063 moles) in
100 ml of 50:50 - T H F: H2O.
A y ello w /o ran g e so lu tio n re s u lte d w hich
g ra d u a lly clea re d u p o n s tir r in g fo r I h r .
A fte r th e d ropw ise ad d itio n of 25
106
ml of SN NaOH, th e solution re g a in e d its y ello w /o ran g e a p p e a ra n c e .
T hen,
a f te r 5 m in u tes, 2.5 g (0.066 moles) of NaBH4 w ere d isso lv ed in 25 ml of SN
NaOH a n d a d d e d dropw ise to th e so lu tio n , lib e ra tin g fre e m e rc u ry .
T he
re a ctio n was allowed to s e ttle b e fo re vacuum filte rin g th ro u g h Celite.
Removal of so lv e n t a t re d u c e d p r e s s u r e y ield ed 3.89 g (0.027 moles) of th e
alcohol m ix tu re
(52% y ie ld ).
GC a n a ly sis in d ic a tes th e s y n : a n ti alcohol
ra tio a s 3 ; I .
M eth o x y m ercu ratio n /d em ercu ratio n of c is-8 -o x a b ic y c lo [4 .3 .0 ]n o n -3 -e n e , [1 ].
T he a lk e n e , [1 ] , (0.435 g , 3.51 moles) was a d d e d to a s tir r in g solution
of 1.12 g (3.51 moles) of m ercu ric a c e ta te in 25 ml of m ethanol to w hich
was ad d ed a c a ta ly tic am ount of n itric a cid .
A fte r s tir r i n g o v e rn ig h t,
0.190 g (3.51 moles) of sodium m ethoxide w a s.a d d e d a n d th e solution was
s tir r e d fo r I h r .
NaBH4 .
T h e n 5 ml of 0.50 M NaOH was a d d e d followed b y ex cess
The re a c tio n was s tir r e d b rie fly , re s u ltin g in a g re y s lu r r y w hich
was allowed to s e ttle a n d th e n vacuum filte re d th ro u g h c e lite .
Removal of
so lv en t a t re d u c e d p r e s s u r e a ffo rd e d 0.484 g (3 .1 0 moles) of a clear liq u id
(88% y ie ld ).
GLC
(13% DECS, 8 'x l/4 " , 130°C) show ed two p e a k s fo r th e
s y n - a n d a n ti- m ethoxy d e riv a tiv e s in th e ra tio 3 : 1 ,
re s p e c tiv e ly .
sy n -m e th o x y d e riv a tiv e , 1221.
1H NMR: 1 .4 3 -1 .2 7 (m, 2H ), 1.9 6 -1 .5 6 (m ethylene en v elo p e, 4H ), 2 .22- 2.10
(m, 1H ), 2.5 0 -2 .2 3 (m, IH ), 3 .2 2 -3 .1 0 (m , 1H ), 3.40 ( s , 3H ), 3 .7 0 -3 .5 9 (d d d ,
2H ), 3 .8 6 -3 .7 5 (m, 2H ).
MS (E l):
M+ = 156, 124, 109, 97, 95, 82, 69 ( b a s e ) , 58, 41.
MS ( C l) :
MH+ = 157, 139, 125 ( b a s e ) , 107.
a n aly sis - HRMS calcu lated fo r C bH16O2 = 156.2267; F ou n d = 156.1206.
107
an ti-m e th o x y d e riv a tiv e , [231.
IH NMR: 1 .4 5 -1 .3 5 (m, 1H>, 2 .7 5 -2 .0 5 (m ethylene en v elo p e, 4H ), 2 .2 0 -2 .1 0
(m, 1H ), 2 .45-2.35 (m, 1H ), 3.20 ( s , 3H ), 3 .3 3 -3 .2 5 (m, 1H ), 3 .6 5 -3 .5 1 (d d d ,
2H ), 3.8 8 -3 .9 3 (d d d , 2 H ).
MS (E l):
M+ = 156, 141, 124, 109, 97, 79, 64, 58, 41 ( b a s e ) .
MS (C l):
MH+ = 157 ( b a s e ) , 125, 107.
a n aly sis - HRMS c alcu lated fo r CeH16O2 = 156.1206; F ou n d = 156.1136.
H ydroboration of 8 -o x a tric y c lo [4 .3 .3 .0 1 n d e c -3 -e n e , [71.
T he p ro p e lla n e , [7 ] , (2 .0 0 g , 0.012 moles) was d isso lv ed in 100 ml of
d r y THF to w hich was ad d ed 4.00 g (0.011 moles) of NaBH4 .
atm osphere was c re a te d a n d th e re a c tio n was cooled to 0°C .
An a rg o n
T hen 1.20
m l,(0.010 moles) of BF3O (C 2H5) 2 w ere sy rin g e d in to th e sy stem .
T he
solution was w arm ed to room te m p e ra tu re an d s tir r e d o v e rn ig h t.
T he
re a ctio n
m ixture
was
th e n
n e u tra liz e d
e x tra c tio n w ith d ichlorom ethan e.
w ith
d ilu te
HCl
followed
by
T he so lv en t was d rie d o v e r MgSO4 an d
th e so lv en t rem oved a t re d u c e p r e s s u r e to y ield 2.30 g (0.016 moles) of th e
c lea r alcohol m ix tu re (80% y ie ld ).
C ap illary GC a n aly sis show ed th e s y n -
an d a n ti- alcohol in th e ra tio 1 : 1 . ,
(s v n )-8 -o x a tric y c lo [4 .3 .3 .0 ]u n d e c -3 -o l, i 25].
IR:
3350, 2930, 2870, 1453, 1180, 1009, 900 cm-1.
1H NMR:
1 .88-1.33 (m ethylene en v elo p e, 12 H ), 3 .8 4 -3 .5 8 (m, 6 H ).
MS (E l):
164 (-H 2O ), 146, 133, 119, 109 (b a s e ), 93, 91, 79, 67, 55, 41,
MS (C l) :
165 ( b a s e ) , 147, 133, 119
a n aly sis - HRMS calcu lated fo r C11H18O2 = 182.2542; F ou n d = 182.1540
108
(a n ti)-8 -o x a tric v c lo [4 .3 .3 .0 ]u n d e c -3 -o l, [261.
IR :
3350, 2930, 2820, 1460, 1170, 995, 900 cm"1 .
1H NMR:
MS (E l):
1 .8 4 -1 .2 3 (m ethylene en v elo p e, 12H ), 3 .6 0 -3 .3 7 (m, 6 H ).
M+ = 182, 164, 151, 133, 123, 119, 109, 93 (b a s e ), 91, 79, 67, 55,
41.
MS (C l):
MH+ = 183, 165 (b a s e ), 147, 135, 121, 109.
a n aly sis - HRMS calcu lated fo r Ca i H18O2 = 182.2542; F ou n d = 182.1323.
E poxidation of 8 -o x a tric y c lo f4 .3 .3 .0 1 u n d e c-3 -en e , (71.
T he p ro p e lla n e , [7 ] , (1.11 g , 6.77 moles) an d 1.40 g (8 .1 3 moles) of
mCPBA w ere com bined w ith 200 ml of d r y chloroform an d s tir r e d a t room
te m p e ra tu re u n d e r a rg o n o v e rn ig h t.
T h e n 30 ml of 10% NaS2O4 w ere ad d ed
to th e m ix tu re . T he o rg a n ic la y e r was s e p a ra te d an d w ashed w ith s a tu ra te d
sodium b ic a rb o n a te followed b y a n a q u eo u s w ash.
T he o rg a n ic la y e r was
d rie d o v e r MgSO4 an d th e so lv en t rem oved a t re d u c e d p r e s s u r e to a ffo rd
0.68 g (3.77 moles) of th e lig h t yellow epoxide m ix tu re (56% y ie ld ).
GLC,
(10% O V IT, 8 'x l/4 " , 180°C ), a n aly sis show ed two p e a k s in th e ra tio 1 : 1 .
To determ ine th e re la tiv e ste re o c h e m istry of th e ep o x id es * th e f ir s t
p e a k to elu te from GLC was cleanly collected an d re d u c e d w ith a ’’p in c h ”
of LAH in 5 ml of d r y T H F.
T he re a c tio n was s tir r e d u n d e r a rg o n
o v e rn ig h t a n d th e n h y d ro ly z e d w ith a small am ount of w a te r.
The sa lts
w ere filte re d off a n d th e so lv en t rem oved a t re d u c e d p r e s s u r e to y ield
only th e a n ti- alcohol as determ in ed b y 1H NMR an d GC/MS.
(s y n )-3 ,4 -e p 6 x v -8 -o x a tric y c lo [4 .3 .3 .0 ]u n d e c a n e , [81.
7lH NMR: 1 .7 0 -1 .4 0 (m, 6H ), 1.77 (d d , 2H ), 2.19 (d d d , 2H ), 3.13 (d d d , MS
(E l):
M+ = 180, 162, 132, 117, 91, 79 (b a s e ).
a n aly sis - HRMS calcu lated fo r C11H18O2 = 180.1150; Found = 180.1155.
109
2H ), 3.73 ( d , 2 H ).
( a n ti) - 3 , 4 -e p o x v -8 -o x a tric y c lo [4 .3 .3 .0 lu n d e c a n e , [ 9 1 .
"lH NMR: 1 .6 5 -1 .4 5 (m, 4H ), 1.92 ( d , 2H ), 2.10 (d d d , 2H ), 3,14 (d d d , 2H ),
3.37 ( d , 2H ), 3.66 ( d , 2H ).
MS (E l):
M+ = 180, 162> 132, 117, 91, 79 (b a s e ).
a n aly sis - HRMS c alcu lated f o r C11H16O2 = 180.1150; Found = 180.1160.
P r e p a r a tio n
of
(p a ra )-n itro b e n z o a te
d e r iv a tiv e s
of
(c is ) - 8 -
oxabicyclo[4 .3 .0 ]n o n -3 -e n e , (11.
T he
m ix tu re
of
th e
sy n -
and
a n ti- alcohols
d e riv e d
from
th e
o y m e rc u ra tio n /d e m ercu ratio n of [1] (3 .8 9 g , 0.0274 moles) was d isso lv ed in
50 ml of d r y p y rid in e a n d a n a rg o n atm o sp h ere was c re a te d .
T hen 5.89 g
(0.0301 moles) of T s C l, re c ry sta lliz e d from h e x a n e , w ere d issolved in
p y rid in e a n d a d d e d dropw ise to th e s tir r i n g solution a t room te m p e ra tu re .
T he re a c tio n was th e n allowed to s t i r o v e rn ig h t, th e n th e solution was
p o u re d o v e r ice w a te r, re s u ltin g in th e form ation of a yellow oil.
x
T his
m ixture was r e f r ig e r a te d fo r s e v e ra l h o u rs w h ereu p o n a solid form ed w hich
was filte re d off an d re c ry sta lliz e d in h e x a n e to yield 6.30 g (0.0208 moles)
of th e w hite p a r a -n itro b e n z o a te m ix tu re (76% y ie ld ).
F lash se p a ra tio n was
em ployed to cleanly s e p a ra te th e s y n - a n d a n ti- p r o d u c ts .
IR , (m ix tu re ): 2930, 2885, 1721, 1717, 1607, 1526, 1349, 1276, 1150, 830, 719
cm- 1 .
s y n - (p a ra )-n itro b e n z o a te d e riv a tiv e of ( c is ) -8 -o x ab icy clo (4 .3 .0 1 n o n -3 -e n e ^
mi.
MP:
127-129°C
xH NMR: 1 .8 4 -1 .6 3 (m ethylene en v elo p e, 6H ), 2 .4 0 -2 .3 0 (m , 2H ), 3 .7 1 -3 .6 4
i
HO
(m, 2H ), 3.87-81 (m, 2H ), 5.04 (m, 1H ), 8 .2 6 -8 .1 3 (d d , 4H ).
MS (E l):
M+ = 291, 261, 231, 150 ( b a s e ) , 141, 124, 94, 79, 69, 55, 41, 28.
a n aly sis - HRMS calcu lated fo r Ci s H17NO5 = 291.30867; Found = 291.1107.
a n ti-(p a ra )-n itro b e n z o a te d e riv a tiv e of ( cis ) -8 -oxabicvclo [4 .3 .0 1 non - 3- e n e ,
[281.
MP:
90-93°C
1H NMR:
2 .0 0 -1 .6 3 (m ethylene en v elo p e, 6H ), 2 .4 0 -2 .2 5 ( d d d , 1H ), 2 .6 0 -
2.45 (d d d , 1H ), 3 .7 4 -3 .6 2 (m, 2H ), 3 .9 5 -3 .8 3 (m, 2H ), 5 .3 2 -5 .2 0 (d d , 1H ), 8 .2 7 r
8.13 ( d d , 4H ).
MS (E l):
M+ = 291, 261, 232, 150 (b a s e ), 141, 124, 107, 94, 79, 69, 55, 41,
28.
a n aly sis - HRMS calcu lated fo r C15H17NO5 = 291.30867; F ou n d = 291.1102.
P re p a ra tio n of to sy la te d e riv a tiv e s of [11.
T he s y n - (p a ra )-n itro b e n z o a te d e riv a tiv e of [1] (0.527 g , 1.81 moles) was
disso lv ed in I ml of diehlorom ethane a n d ad d ed to 35 ml of 80% aq u eo u s
ethanol th a t was 0.50% b y w eight in KOH (2 .0 g of KOH in a solution of
200 ml of a b so lu te eth an o l an d 50 ml d istilled w a te r).
s tir r e d o v e rn ig h t a t room te m p e ra tu re .
T he re a ctio n was
T h e n , m ost of th e so lv en t was
rem oved a t re d u c e d p r e s s u r e ,a n d 15 ml of diehlorom ethane w ere ad d ed to
th e re s id u e .
T he o rg a n ic la y e r was co llected , d rie d of MgSO4 , an d th e
so lv en t rem oved a t re d u c e d p r e s s u r e y ie ld in g 0.169 g (1 .9 1 moles) of th e
s y n -alcohol (66% y ie ld ).
T he IR , 1H NMR, a n d MS (E I) s p e c tra of th is com pound w ere id en tical
to th o se of th e p re v io u s ly re p o rte d s y n -alcohol.
In
a sim ilar fa sh io n ,
saponification of th e a n ti- (p a ra ) -n itro b e n z o a te
d e riv a tiv e of [1] (1 .0 0 g , 3.44 moles) a ffo rd e d 0.255 g , (1 .8 0 m oles), of th e
Ill
a n ti- alcohol (52% y ie ld ).
A gain, th e IR , 1H NMR, a n d MS (E I) s p e c tra of th is compound w ere
id en tical to th a t of th e p re v io u s ly re p o rte d s y n -alcohol.
T he s y n -alcohol, (0.169 g 1.91 moles) was th e n d isso lv ed in 20 ml of
d r y chloroform to w hich was ad d ed 0.20 ml (2 .4 moles) of p y r id in e .
T he
solution was cooled to 0°C an d 0.340 g (1.79 moles) of T sC l w ere ad d ed in
small p o rtio n s.
T he re a c tio n was th e n warmed to room te m p e ra tu re an d
s tir r e d u n d e r a rg o n o v e rn ig h t.
A so lu tio n of 40 ml of e th e r a n d 10 ml of
w ater w ere a d d e d to th e re a ctio n m ix tu re , w hich was th e n w ashed w ith 2 N
HCL, 5% sodium b ic a rb o n a te , a n d w a te r, re s p e c tiv e ly .
T he o rg an ic la y e r
was d rie d o v e r MgSO4 a n d th e so lv en t rem oved a t re d u c e d p r e s s u r e to
yielded 0.505 g of th e c ru d e p ro d u c t.
of T s Cl.
TLC a n aly sis in d ic a te d th e p re se n c e
F lash s e p a ra tio n w as, th e re fo re , employed to c lean ly isolate th e
s y n -to s y la te .
T he p ro d u c t was c ry sta lliz e d in a so lu tio n of h ex an e : dichlorom ethane
in th e re la tiv e ra tio 50 : I , re s p e c tiv e ly .
With th e id e n tic al p ro c e d u re re p o rte d ab o v e, 0.250 g (1 .7 6 moles) to
th e a n ti- alcohol w ere d isso lv ed in 20 ml .Of chloroform to w hich was ad d ed
0.29 ml (3.52 moles) of p y rid in e a n d 0.503 g (2.64 mmoles)
TsC L
T he a n ti- to sy la te was clean ly a ffo rd e d 0.44 g (1 .5 moles) fla sh
s e p a ra tio n .
T he a n ti- p ro d u c t was a clear oil th a t could n o t b e c ry sta lliz e d .
112
(s y n )-to s y la te d e riv a tiv e of (c is )-8 -o x a b ic v c lo f4 .3 .0 1 n o n -3 -e n e , [191.
C12 I C9
F ig u re 76.
ORTEP d raw in g of [19].
Table 24. Atomic co o rd in ates (xlO 4) a n d iso tro p ic th erm al p a ram eters
(A 0XlO3) of [19].
X
y
Z
U
C d)
224(4)
3851(2)
4927(3)
78(1)*
C (2)
2641(5)
3901(2)
5392(3)
79(1)*
C (3)
3228(5)
3340(2)
6130(2)
73(1)*
C (4)
2930(6)
2666(2)
5613(3)
88(1)*
C(5)
519(5)
2580(2)
5171(3)
92(2)*
C(6)
-299(6)
3153(2)
4479(3)
80(1)*
C (7)
618(7)
3194(2)
3404(3)
103(2)*
0 (1 )
644(5)
3888(2)
3132(2)
113(1)*
C(8)
-168(8)
4275(2)
3959(3)
105(2)*
0 (2 )
5616(4)
3424(1)
6489(2)
93(1)*
113
(T able 24. c o n tin u e d )
S
6286(1)
3444(1)
7696(1)
83(1)*
0 (3 )
8675(4)
3483(2)
7745(2)
111(1)*
0 (4 )
5241(4)
2913(1)
8210(2)
104(1)*
C(9)
5213(5)
4212(2)
8096(2)
70(1)*
C(IO)
6304(5)
4799(2)
7913(3).
94(2)*
C ( I l)
5423(8)
5397(2),
8217(3)
106(2)*
C(12)
3497(7)
5426(2)
8733(3)
97(2)*
C(13)
2452(6)
4831(2)
8903(3)
98(2)
C(14)
3278(6)
4225(2)
8601(3)
85(1)*
C(15)
2536(9)
6069(2)
9086(4)
139(2)*
* E q uivalent
iso tro p ic
U d efin ed
as
one th ir d
of th e
tra c e
o rth o g o n alised Uy te n s o r .
Table 25.
B ond le n g th s (A 0) of [1 9 ].
C (l)- C ( 2 )
1.533(5)
C (I)-C (S )
1.504(5)
C (3 )-C (4 )
C (D - C O )
•
.
1.529(5)
C (2 )-C (3 )
1.490(5)
1.503(5)
C (3 )-0 (2 )
. 1.486(4)
C (4 )-C (5 )
1.527(5)
C (5 )-C (6 )
1.505(5)
C (6 )-C (7 ).
1,523(5)
C ( 6 ) -H (6)
0.960(7)
C (7 )-0 (l)
1.428(5)
O (I)-C (S )
1.426(5)
C (9 )-C (1 0 )
1.369(5)
C (IO )-C (Il)
1.373(6)
0 (2 )-S
1.568(2)
8 -0 (3 )
1.436(2)
S-O (4)
1:419(3)
S -C (9 )
1.754(4)
C (12)-C (13)
1.367(6)
C (1 2 )-C (1 5 )
1.490(6)
C (13)-C (14)
1.372(6)
,
.
. 114
Table 26. B ond a n g les (° ) of [1 9 ].
H ( l) - C ( l) - C ( 2 )
110.7(17)
H ( l) - C ( l) - C ( 6 )
113.4(20
C ( 2 )- C ( l)-C (6 )
111.6(3)
H (I)-C (I)-C (S )
108.3(19)
C ( 2 )- C ( l)-C (8 )
111.7(3)
G (6 )-G (l)-C (8 )
100.8(3)
C ( l)- C ( 2 )-C (3 )
111.7(3)
C (2 )-C (3 )-H (3 )
113,8(20)
C (2 )-C (3 )-C (4 )
112.1(3)
H (3 )-C (3 )-C (4 )
108.4(20)
C (2 )- C ( 3 )-0 (2 )
106.8(3)
H (3 )-C (3 )-0 (2 )
106,8(17)
C (4 )- C ( 3 )-0 (2 )
108.6(3)
C (3 )-C (4 )-C (5 )
110.0(3)
C (4 )-C (5 )-C (6 )
113.2(3)
C ( l)- C ( 6 )-C (5 )
114.8(3)
C (l)- C ( 6 )-H (6 )
102.6(22)
C (5 )-C (6 )-H (6 )
112.2(22)
C ( l)- C ( 6 )-C (7 )
102.2(3)
C (6 )-C (7 )-C (7 )
116.7(3)
H (6 )-C (6 )-C (7 )
106.8(21)
C ( 6 ) - G ( 7 ) - 0 ( l)
106.5(3)
C ( 7 ) - 0 ( l) - C ( 8 )
109.4(3)
C ( I ) -C (S )- O (I)
105.5(3)
C ( 3 )- 0 (2 )-S
118.7(2)
0 (2 )-S -0 (3 )
103.2(1)
0 (2 )-S -0 (4 )
110.4(1)
0 (3 )-S -0 (4 )
119.8(2)
0 (2 ) -S -C (9 )
103.7(1)
0 (3 ) -S -C (9 )
109.2(2)
0 (4 ) -S -C (9 )
109.3(2)
S -C (9 )-C (1 0 )
120.2(3)
S -C (9 )-C (1 4 )
119.8(3)
C (1 0 )-C (9 )-C (1 4 )
119.9(3)
C ( 9 ) -C (1 0 )-C (11).
119.5(4)
C (1 0 )- C (1 1 )- C (12)
121 .9 (4 )
C (ll) -C (1 2 )-C (1 3 )
117,0(4)
C (1 1 )-C (1 2 )- C (15)
122.7(4)
C (l3 )-C (1 2 )-C (1 5 )
120.3(4)
C (1 2 )-C (1 3 )- C (14)
122.5(4).
C (9 )-C (1 4 )-C (1 3 )
119.1(4) .
IH NMR: 1 .9 2 -1 .5 2 (m ethylene en v elo p e, 6H ), 2 .3 1 -2 .1 2 (m , 2H ), 2.42 ( s ,
3H ), 3 .6 7 -3 .5 2 (m , 2H ), 3.85^3.74 Cm, 2H ), 4.51 (m, 1H ), 7 .3 7 -7 .2 8 ( d , 2H ),
...
:
115
7 .83-7.7 5 ( d , 2H ).
MS (E I):. 124 (-TsO H )., 106, 93, 91, 79 (b a s e ), 69, 54, 41.
MS (C l) :
MH+ = 297 ,.1 7 3 , 141; 125 ( b a s e ) , 117.
a n aly sis - HRMS calcu lated fo r C15H20SO4 = 296.3897; Found = 296.1026.
(a n ti) -to s y la te d e riv a tiv e of ( cis ) -8 -o x ab icv clo 14.3.01 n o n -3 -e n e , 1311.
1H NMR: 1 .9 5 -1 .3 3 (m ethylene en v elo p e, 6 H ), 2 .3 1 -2 .1 8 (d d d , IH ), 2.43 ( s ,
3H ), 3.5 8 -3 .4 5 (m, 2H ), 3 .8 3 -3 .7 3 (m, 2H ), 4.67 (m, IH ), 7 .3 6 -7 .2 6 (d , 2H ),
7.8 2 -7 .7 2 ( d , 2H ).
MS (E l):
124 (-T sO H ), 106, 93, 91, 79 (b a s e ), 69, 54, 41.
MS ( C l) :
MH+ = 297, 173, 141, 125 ( b a s e ) , 117.
a n aly sis - HRMS calcu lated fo r C13H20SO4 = 296.3897; F o u n d = 296.1159.
P re p a ra tio n
of
( p a ra )-n itro b e n z o a te
d e r iv a tiv e s
of.
8-
from
th e
oxatricy clo r 4 .3 .3 .0 1 u n d e c -3 -e n e .
A
m ix tu re
of
th e
syn-
and
a n ti- alcohols
d e riv e d
h y d ro b o ra tio n of [7] (2 .3 0 g , 0.0126 moles) was d isso lv ed in 50 ml of d r y
p y rid in e to w hich was a d d e d 2.80 g (0.0150 moles) of PNBCl in 25 ml of
p y rid in e .
o v e rn ig h t.
T he re a c tio n was s tir r e d u n d e r a rg o n a t room te m p e ra tu re
T he solution was th e n p o u re d o v e r ice w a te r a n d a w hite
p re c ip ita te form ed w h ich was filte re d o ff, y ield in g 3 .5 g of th e c ru d e
p ro d u c t.
TLC
a n aly sis
in d ic a ted
th e
p re se n c e
th e
d e sire d
p a ra -
n itro b en z o ates a n d p a r a -n itro b en z o v l c h lo rid e . F lash c h ro m a to g ra p h y was
em ployed to cleanly isolate th e is o m e rs /
s y n -3 - (p a ra ) -h itro b en zo ate-8 -o x atricy clo T 4 .3 .3 . O lu h d ecan e. 1291.
MP:
119-121 °C
1HNMR: 1 .8 3 -1 .5 3 (m ethylene en v elo p e, I OH), 2.08 (m , 2H ), 3 .8 7 -3 .6 1 (d q ,
4H ), 5.19 (m, IH ) , 8 .2 9 -8 .1 5 (d d d , 4H ).
116
MS (E l):
M+ = 164 (-PN B O H ),' 146, 133, 119, 105, 91 ( b a s e ) , 79, 77.
MS (N C I):
M+ = 331, 299, 167.
a n aly sis - HRMS calcu lated fo r C18H21NO5 = 331.3712; F ou n d = 331.1415.
a n ti- 3 - ( p a r a ) -n itro b e n z o a te -8 -o x a tric v c lo r4 .3 .3 .O lu n d e c -3 -e n e . ra n ).
1H NMR: 1 ,8 4 -1 .5 9 (m ethylene en v elo p e, I OH), 2.1 (m, 2H ), 3 .8 6 -3 .6 3 (d q ,
4H ), 5.20 (m, 1H ), 8 .2 9 -8 .1 6 (d d d , 4H ).
MS (E l):
M+.= 164 (-PN B O H ), 146, 133, 119, 105, 91 ( b a s e ) , 79, 77.
MS (N C I):
M+ - 331, 299, 167.
a n aly sis - HRMS calcu lated fo r C18H21NO5 = 331.3712; F ou n d = 331.2563.
P re p a ra tio n of to sy la te d e riv a tiv e s of f71.
T he s y n -p a ra -n itro b e n z o a te d e riv a tiv e of [7] (0.380 g ,
1 .1 5
moles) was
disso lv ed in 2 ml of dichlorom ethane a n d th e n a d d e d to a 80% aq u eo u s
eth an o l solution th a t was 0.5% b y w eig h t in KOH.
s tir r e d o v e rn ig h t.
was
a d d ed
to
T he re a ctio n was
Most of th e so lv en t was s trip p e d , th e n 10 ml of w a ter
th e
re s id u e .
T he
solution
was
e x tra c te d
w ith
dichlorom ethane, th e o rg a n ic s d rie d , a n d th e so lv en t s trip p e d to yield 0.20 g
(1,09 moles) of th e c le a r alcohol (73% y ie ld ).
T he IR , GC/MS, an d 1H
NMR of th is com pound w ere id en tic al to th e p re v io u s ly re p o rte d s y n alcohol.
S aponification, re p o rte d in th e p re p a ra tio n of to sy la te d e riv a tiv e s of
[1 ], of th e a n ti- p a ra -n itro b e n z o a te of [7] (0.450 g , 1.35 moles) re s u lte d in
0.18 g , (1.26 moles)
of th e a n ti-alcohol (93% y ie ld ).
T he sy n -alco h o l (0.130 g , 0.71 moles) was d isso lv e d in 10 ml of
dichlorom ethane to w hich was ad d ed 0.12 ml (1 ,4 moles) o f p y rid in e .
T he
solution was cooled to O0C a n d 0.16 g (0 .8 4 moles) of T sC l was ad d ed in
small p o rtio n s .
T he re a c tio n was w arm ed to room te m p e ra tu re an d s tir r e d
117
o v e rn ig h t.
A fte r th e id en tic al w orkup re p o rte d a b o v e , 0.200 g of a yellow
oil w ere o b ta in e d .
1H NMR an d TLC a n aly sis in d ic a ted th e p re se n c e of th e
d e sire d p a ra -n itro b e n z o a te along w ith a minor am ount of TsCL
ch ro m ato g rap h y was em ployed to isolate th e p ro d u c t.
Flash
C ry stallizatio n of th e
p ro d u c t was accom plished in hex an e : dichlorom ethane in a re la tiv e ra tio of
50 : I , re s p e c tiv e ly .
In a sim ilar fa sh io n , 90 mg of th e a n ti- alcohol (0 .4 9 moles) w ere
d e riv a tiz e d y ie ld in g 0.160 g of a yellow liq u id .
T sC l was in d ic a ted as a
m inor p ro d u c t b y TLC a n d fla sh c h ro m ato g rap h y was em ployed to isolate
th e d e sire d p ro d u c t.
T he isolated p ro d u c t was a c le a r oil th a t would not
c ry s ta lliz e .
s y n -3 -to s v l-8 -o x a tric y c lo [4 .3 .3 .0 lu n d e c a n e , [241.
1H NMR: 1 .9 0 -1 .3 0 (m ethylene en v elo p e, 12H ), 2.42 ( s , 3H ), 3.72 -3 .5 5 (d q ,
4H ), 4.65 (m , 1H ), 7 .3 5 -7 .3 0 ( d , 2H ), 7 .8 2 -7 .7 7 ( d , 2H ).
MS (E l):
M+ = 164 (-T sO H ), 146, 133, 119, 105, 91 ( b a s e ) , 79, 77.
MS (C l): MH+ = 337, 181, 165 (b a s e ), 147, 135, 117.
a n aly sis - HRMS calcu lated fo r Ci s HaoSO4 = 336.4259; Found = 336.1465.
X -ra y a n a ly sis:
F ig u re 77. ORTEP d raw in g of [2 4 ].
V
118
T able 27. Atomic c o o rd in a tes (xlO 4) an d iso tro p ic th erm al p a ra m ete rs
(A 0XlO3) f o r [2 4 ].
X
y
Z
U
C d)
7888(4)
6234(4)
5984(3)
53(2)*
C (2)
7622(5)
7453(4)
6392(3)
61(2)*
C (3)
7352(4)
7335(4)
7267(3)
49(2)*
C (4)
8504(5)
6696(4)
7896(3)
68(2)*
C (5)
8673(5)
5434(5)
7537(3)
73(2)*
C (6)
8870(4)
5445(4)
6622(3)
53(2)*
C (7)
10217(4)
5896(5)
6520(3)
81(2)*
O (I)
10018(3)
6470(5)
5700(3)
91(2)*
C (8)
8650(4)
6431(5)
5270(3)
73(2)*
C (9)
6618(4)
5516(4)
5682(3)
69(2)*
C(IO)
7089(5)
4205(5)
5739(4)
104(3)*
C ( I l)
8514(6)
4170(4)
6202(4)
86(3)*
0 (2 )
7279(3)
8563(3)
7607(2)
63(1)*
S
6005(1)
8925(1)
7937(1)
56(1)*
0 (3 )
6310(3)
101000(3)
8282(2)
73(1)*
0 (4 )
5688(3)
7993(3)
8476(2)
67(1)*
C(12)
4748(4)
9015(4)
6984(3)
. 48(2)*
C (13)
4670(5)
, 10006(4)
6449(3)
. 66(2)*
C (14)
3692(6)
10059(5)
5699(4)
81(2)*
C (15)
2768(5)
91489(5)
5470(3)
74(2)*
119
(T able 27. c o n tin u ed )
C(16)
2853(5)
8179(4)
6005(3)
67(2)*
C(17)
3831(4)
8096(4)
6759(3)
58(2)*
C(18)
1705(6)
9227(6)
4632(4)
121(3)*
* E q u iv alen t iso tro p ic
U defined
as
one th ir d
of th e
tra c e
o rth o g o n alised Uy te n s o r .
T able 28.
B ond le n g th s (A °) fo r [2 4 ].
C (l)- C ( 2 )
1.553(6)
C (l)- C ( 6 )
1.529(6)
C (I)-C (S )
1.527(7)
C (I)-C (S )
1.512(6)
C (2 )-C (3 )
1.473(7)
C (3 )-H (3 )
0.960(32)
C (3 )-C (4 )
1.534(6)
C (3 )-0 (2 )
1.477(5)
C (4 )-C (5 )
1.540(7)
C (5 )-C (6 )
1.501(7)
C (6 )-C (7 )
1.5177)
C ( 6 ) - C ( ll)
1.574(7)
C ( 7 ) - 0 ( l)
1.414(6)
O (I)-C (S )
1.416(5)
C (9 )-C (1 0 )
1.535(7)
C (IO )T C (Il)
1.481(7)
G (2)-S
1.569(4).
8 -0 (3 )
1.425(3)
8 -0 (4 )
1.424(3)
S-C (12)
1.746(4)
C (12)-C (13)
1.380(6)
C (12)-C (17)
1.382(6)
C (13)-C (14)
1.366(7)
C (1 4 )-C (1 5 )
1.381(8)
C (15)-C (16)
1.360(7)
C (1 5 )-C (1 8 )
1.511(7)
C (16)-C (17)
1.373(6)
.
of th e
. 120
T able 29.
B ond a n g les (? ) of [2 4 ].
C (2 > C (1 )-C (6 )
112.5(3)
C (G )-C (I)-C (S )
101.1(3)
C (G )-C (I)-C (S )
107.2(4)
C ( 8 )- C ( l)-C (9 )
1 1 3 .3 (3 ).
C ( l)- C ( 2 )-C (3 )
113.5(4)
C (2 )rC (3 )-H (3 )
114.0(28)
C (2 )-C (3 )-C (4 )
111.3(4)
H (3 )-C (3 )-C (4 )
110.1(24)
C (2 )- C ( 3 )-0 (2 )
107.0(3)
H (3 )- C ( 3 )-0 (2 )
107.2(25)
C (4 )- C ( 3 )-0 (2 )
107.0(3)
H (3 )- C ( 3 )-0 (2 )
108.7(3)
C (4 )-C (5 )-C (6 )
113.4(4)
C (I)-C (G )-C (S )
114.9(4)
C (l)- C ( 6 )-C (7 )
102.9(4)
C (5 )-C (6 )-C (7 )
115.6(4)
C (I ) - C ( G ) - C ( I l)
100.8(3)
C (S )-C (G )-C (Il)
109.1(4)
C (T )-C (G )-C (Il)
112.6(4)
C (G )-C (T )-O (I)
107.5(3)
C ( 7 ) - 0 ( l) - C ( 8 )
110.0(4)
C (I) - C ( S ) - O ( I )
105.9(3)
C ( I ) -C ( 9 ) -C (IO )
104.3(4)
: C ( 2 )- C ( l)-C (8 )
..
•
C ( 2 )- C ( i)-C (9 )
C( 9 ) -C (1 0 )- C (11)
. 110.4(4)
■ i l l . 8(4)
108.5(4)
C (G )-C (Il)-C (IO )
107.0(4)
C (3 )- 0 (2 )-S
118.3(3)
0 (2 )-S -0 (3 )
103.6(2)
0 (2 )-S -0 (4 )
109.4(2)
0 (3 )-S -0 (4 )
120.2(2)
0 (2 )-S -C (1 2 )
103.9(2)
0 (3 )-S -C (1 2 )
109.3(2)
0 (4 )-S -C (1 2 )
109.2(2)
S -C (1 2 )-C (1 3 )
119.9(3)
S -C (1 2 )-C (1 7 )
120.4(3)
C (1 3 )-C (1 2 )-C (1 7 )
119.7(4)
C (1 2 )-C (1 3 )-C (1 4 )
119.4(4)
C (IS )-C (1 4 )- C (15)
121.3(5)
C (1 4 )-C (IS )-C (IG )
118.6(4)
C (14)- C (1 5 )- C (18)
120.2(5)
C (1 6 )-C (1 5 )-C (1 8 ) .
121.2(5)
C (IS )-C (1 6 )- C (17)
121.3(4)
C (1 2 )- C ( 1 7)- C (16)
119.6(4)
121
a n ti-3 -to s y l-8 -o x a tric v c lo [4 .3 .3 . Q Jundecane, [321.
.
-
1H NMR: 1 .9 1 -1 .4 0 (m ethylene en v elo p e, 12H ), 2.43 ( s , 3H ), 3 .7 5 -3 .5 3 (m,
4H ), 4.61 (m, 1H ), 7 .3 4 -7 .2 9 ( d , 2H ), 7 .8 1 -7 .7 6 ( d , 2H ).
MS (E l):
M+ = 164 (-T sO H ), 146, 133, 119, 105, 91 ( b a s e ) , 79, 77.
MS (C l) : MH+ = 337, 181, 165 ( b a s e ) , 147, 135, 117.
a n aly sis - HRMS calcu lated fo r C^5 H 2 0 SO4 = 336.4259; F ou n d = 336.1469.
Mass s p e c tra l d a ta on 2 -m e th o x y -8 -o x atricv c lo [4 .3 . 3 . O lu n d ecan e, [341.
MS (E l):
M+ = 164, 146, 135, 120, 109 ( b a s e ) , 105, 91, 79, 77, 67, 55, 41.
MS (C l): MH+ = 197, 165 ( b a s e ) , 147, 135, 121, 109.
a n aly sis - HRMS calcu lated fo r C1 2 H 2 0 Oav = 196.2916; fo u n d = 196.1462.
P re p a ra tio n of (c is )-l,6 -d ic a rb o m e th o x v -3 -m e th y l-8 -o x a b ic v c lo f4 .3 .0 1 n o n -3 e n e , [371.
A solution of 100 ml of d r y TH F, 56.0 ml (2 .5 e q u iv a le n ts ) of 2.6 M n BuLi an d 18.8 ml (1 .1 e q u iv alen t) of diisopropylam ine w as s tir r e d u n d e r
a rg o n a t -78° C fo r 15 m in u te s.
T h e n 11.4 g (0.0538 moles) of c is - 3-
m e th y l-1 , 6 -d icarb o m eth o x y cy clo h ex -3 -en e w ere ad d ed d ro p w ise, c re a tin g a
b r ig h t r e d so lu tio n .
A fte r th e a d d itio n was com plete, th e solution was
s tir r e d fo r 15 m inutes a n d warmed to -10° C a n d 6.00 ml (1 .1 eq u iv alen t)
of 1 , 3-dibrom opropane w ere ad d ed d ro p w ise . T he re a c tio n was th e n warmed
to room te m p e ra tu re a n d s tir r e d fo r 2.5 h o u r s .
A fte r w o rk u p , a c lea r
liquid re s u lte d w hich was vacuum d istille d to yield 6.24 g (46% y ield ) of
th e d e sire d d ie s te r.
BP 0
IR:
.5
= 108-110° C
2930, 1732, 1434, 1251, 1232, 1207, 1173 cnT1 .
1H NMR:. 2 .5 2 -1 .5 0 (1 3 H ), 3.60 ( s , 3 H ), 3.65 ( s , 3H ), 5.29 ( b s , 1H ).
MS (E l): .220 (-M eO H ), 192, 161, 133 ( b a s e ) , 105, 91, 77, 59, 41.
122
P re p a ra tio n of 3-m eth y l-8 -o x atric y clo [4 .3 .3 .0 1 u n d e c -3 -e n e , [351.
T he d ie s te r, [3 7 ], (5 .1 0 g , 0.0202 moles) was a d d e d to 0.92 g (0.0243
moles) of LAH in 50 ml of d r y T H F.
T he re a ctio n was s tir r e d u n d e r a rg o n
o v e rn ig h t a n d th e n q u e n ch e d w ith a small am ount of w et e t h e r .
lithium
rem oved
sa lts
at
w ere
su ctio n
re d u c e
filte re d
p re ssu re .
off an d
T he
most of th e
re s id u e
was
T he
so lv en t was
e x tra c te d
w ith
dichlorom ethane w hich was d rie d a n d s trip p e d y ie ld in g 3.37 g (0.0171
moles) of th e c le a r diol.
IR a n aly sis confirm ed th e diol fu n c tio n a lity .
T he diol (3.37 g , 0.0171 moles) was combined w ith 50 ml of d r y
p y rid in e a n d h e a te d to re flu x u n d e r a rg o n .
T h en 3.58 g (0.0188 moles) of
TsCL d isso lv ed in 30 ml of p y rid in e w ere ad d ed dro p w ise to th e s tir r in g
so lu tio n .
A fte r w o rk u p , vacuum d istillatio n a ffo rd e d 2.10 g (0.0118 moles)
of th e d e sire d p ro p e lla n e , h a v in g a cam phor-like fra g ra n c e (67% y ie ld ).
BP1 . 5 = 67-69° C
IR:
2952, 2927, 2863, 2836, 1446, 1084, 1061, 944 C nr1 .
1HNMR: 1 .7 8 -1 .4 0 (m ethylene e n v e lo p e ), 1.95 (b s , 3H ), 3 .5 6 -3 .4 3
(m,
4H ), 5.47 ( t , 1 H ).
MS (E l):
M+ = 178, 160, 147, 145, 133, 119, 105 ( b a s e ), 91, 79, 67, 53, 41.
a n aly sis - HRMS calcu lated fo r C12H18O = 178.2767; fo u n d = 178.1355.
H ydrogenation of 3 -m e th y l-8 -o x a tric y c lo [4 .3 .3 .o lu n d e c - 3 -e n e , [35].
100 mg of [35] w ere combined w ith 10 mg of 5% P t/A l c a ta ly s t an d 10
ml of a b so lu te e th an o l.
T he re a ctio n v e sse l was sh a k e n u n d e r 20 p s i of H2
a t room te m p e ra tu re fo r 12 h o u rs .
T he c a ta ly s t was th e n filte re d off an d
p e ak in te g ra tio n b y GC/MS in d ic a te d th e re d u c e d p ro d u c ts w ere form ed in a
ra tio of 3 : I , re s p e c tiv e ly .
123
minor p ro d u c t
MS (E l):
M+ = 180, 162, 149, 135 (b a s e ), 121, 107, 95, 93, 79, 67, 53, 41.
a n aly sis - HRMS calcu lated fo r C12H20O1 = 180.2926; fo u n d = 180.1524.
major p ro d u c t
MS ( E I ) :
M+ = 180, 149, 135 ( b a s e ) , 121, 107, 95, 93, 79, 67, 55, 41.
a n aly sis - HRMS calcu lated fo r. C12H20O1 = 180.1524; fo u n d = 180.1507.
-
^
'
'
'-
/
:
-. .
- ' .
'
-
r
. = /
'
:
\
' :
' -
P re p a ra tio n of (c is)-8 -6 x ab icv lo f4 .3 .0 1 n o n T 2 -ie n e , [ 1 3 j. ,
T he m ix tu re
of to sy la te s
d e riv e d from
[1]
(
'
-
:
.
-
30 micro I) w ere
re p e a te d ly in je c te d onto a p re p a ra to ry GC (SE -30, 10' x 1 /4 " , column tem p.
= 150 °C , in jection p o r t tem p. - 250°C) an d th e olefins [1] a n d [13] in th e
re la tiv e ra tio of I : 4 , re s p e c tiv e ly , w ere co llected.
1H NMR: 1 .7 8 -1 .4 5 (2H , m ), 2.0 5 -1 .9 5 (2H , m ), 2 .4 1 -2 .3 0 (1H , m) 2 .7 3 -2 .6 0
(1H , m ), 3 .6 3 - 3.40 (2H , m ), 3 .9 7 -3 .9 0 (2H , m ), 5 .6 8 -5 .5 8 (1H , m ), 5 .8 5 -5 .7 8
(1H, m ).
MS (E l):
M+ = 124, 94, 91, 79 ( b a s e ), 77, 66, 41.
MS ( C l) :
MH+ = 125 (b a s e ), 107.
a n aly sis - HRMS calcu lated fo r Cs H12O1 = 124.1842; fo u n d = 124.0888.
P re p a ra tio n of 8 -o x a tric y lo [4 .3 .3 .0 ]u n d e c -2 -e n e , [3 3 ].
A m ixture
of th e to sy la te s
d e riv e d from
[7]
(30 micro I) w ere
re p e a te d ly in je c te d onto a p re p a ra to ry GC (SE -30, 10' x 1 /4 " , column tem p.
= 175° C , in jection p o r t tem p. = 250° C) a n d th e olefins [7] a n d [33] in th e
re la tiv e a re a of I : 4, re s p e c tiv e ly , w ere co llected.
xHNMR: 2 .0 0 -1 .4 5 (10H, m ), 3 .7 5 -3 .5 0 (4H , m ), 5 .7 0 -5 .6 1 (1H , d d ) ,
5.85 (m, 1H ).
MS (E l): M+ = 164, 146, 133, 119, 105, 91 ( b a s e ) , 77, 65, 41.
MS ( C l ) : MH+ = 165, 147, 133, 119.
124
a n a ly sis - HRMS c alc u la te d fo r C11H16O1 = 164.1197; fo u n d = 164.1208.
P re p a ra tio n of p h th a la n , [401.
P h th alic a n h y d r id e , [3 9 ], (10.0 g , 0.066 moles) w as d isso lv ed in 50 ml
of d r y THF a n d a d d e d dropw ise to a so lu tio n of 50 ml of THF an d 2.81 g
(0.074 moles)
of LAH a t 0° C.
T he re a ctio n was w arm ed to room
te m p e ra tu re a n d s tir r e d fo r 12 h o u r s .
A fte r th e p re v io u s ly d e sc rib e d
w o rk u p , 7.25 g (0.044 moles) of th e diol, a s d eterm in ed b y IR , was iso lated .
T he diol was th e n disso lv ed in 50 ml of p y rid in e a n d h e ate d to a
g e n tle re flu x u n d e r a rg o n .
p y rid in e
w ere
added
T hen 10.3 g (0.048 moles) of T sC l in 30 ml of
dropw ise
p re v io u s ly d e sc rib e d w o rk u p ,
to
th e
2.02 g
s tir r in g
so lu tio n .
(0.017 moles)
A fte r
th e
of p h th a la n w ere
is o la te d .
IR:
1696, 1684, 1675, 1489, 1455, 1372, 1219, 1088, 1043, 1015 cm”1 .
1H NMR:
5.10 ( b s , 4H ), 7.25 (b s , 4H ).
MS (E l) :
M+ = 120, 119, 91 ( b a s e ) , 77, 65, 63, 51.
P re p a ra tio n of 6 - 1 , 6 -A -3 ,4 -8 -o x ab icy clo [4 .3 .0 ] n o n d ie n e, [4 1 ].
To 200 ml of fr e s h ly d istilled ammonia, 0.146 g (0 .0 2 0 moles) of
lithium w ere a d d e d in small c h u n k s.
b r ig h t b lu e .
T h e n 1.1 ml (0.010 moles) of p h th a la n in a n h y d ro u s e th e r
w ere ad d ed d ro p w ise .
m in u te s.
d is s ip a te d .
Im m ediately th e so lu tio n tu rn e d
A fte r ad d itio n th e so lu tio n was allow ed to s tir fo r 20
A bsolute eth an o l was th e n a d d e d dropw ise u n til th e blue color
T h e n lithium (2 e q u iv a le n ts ) was ag ain a d d e d to th e solution
w hich re g a in e d its b r ig h t b lu e color.
T he solution w as allow ed to s tir fo r
an ad d itio n 20 m in u te s, a t w hich time a b so lu te e th an o l w as once a g ain
ad d ed dropw ise to d is c h a rg e th e b lu e co lo r.
T he r e s u ltin g solution was
p o u re d o v e r 50 g of c ru s h e d ice to w hich was a d d e d 200 ml of d ie th y l
125
e th e r .
Most of th e ammonia was allowed to e v a p o ra te , th e solution was
n e u tra liz e d an d th e n e x tra c te d w ith dichlorom ethane. T he so lv e n t was d rie d
an d .rem o v ed a t re d u c e d p r e s s u r e to y ield 0.71 g .(5 .8 2 moles) of th e d e sire d
p ro d u c t (58% y ie ld ).
xH NMR:
2.65 ( s , 4H ), 4.53 ( s , 4H ), 5.76 ( s , 2 H ).
MS (E l):
M+ = 122, 104, 93 ( b a s e ) , 91, 77, 65, 51, 41.
an aly sis - HRMS calcu lated fo r C8H10O = 124.18424; fo u n d = 122.0729.
P re p a ra tio n of A - 1 ,6 -8 -oxabicyclo [4 .3 .0 1 n o n e n e , 1151.
A solution of 100 ml of. a b so lu te e th an o l a n d 0.200 g of 10% P d / C
c a ta ly s t w ere s a tu r a te d w ith H2 g a s.
A fte r s a tu ra tio n , th e H2 p r e s s u r e
was re d u c e d to one atm osphere an d 0.40 ml of th e d ie n e ,
[4 1 ], w ere
sy rin g e d in to th e re a c tio n v e sse l a n d th e solution was s tir r e d a t room
te m p e ra tu re fo r 15 m in u tes.
T he c a ta ly s t was filte re d off a n d th e so lv en t
rem oved a t re d u c e d p r e s s u r e to y ield th e re d u c e d p ro d u c ts [12] a n d [15] in
a 5 : I ra tio , re s p e c tiv e ly , as d eterm in ed b y p re p a ra tiv e GC (13% DEGS, 10'
x 1 /4 " , T= 130° C ).
1H NMR:
1.66 (m, 4H ), 1.94 ( b s , 4H ), 4.48 ( b s , 4H ).
MS (E l):
M+ = 124, 95 (b a s e ), 93, 91, 81, 77, 67, 65, 55, 53, 41.
a n aly sis - HRMS calcu lated fo r CaH12O1 = 124.0889; fo u n d = 124.0889.
P re p a ra tio n of ( c is ) - 7 , 7 , 9 , 9 -te tra d e u te ro -8 -o x a b ic y c lo [4 .3 .0 ]n o n -3 -e n e , [4 2 ].
PhthaU c a n h y rid e (1 .5 0 g , 9.86 moles) was d isso lv ed in 10 ml of d r y
THE an d a d d e d a t 0° C .to 0.66 g (15.8 moles) of LAD.
T he re a ctio n was
warmed to room te m p e ra tu re a n d s tir r e d u n d e r a rg o n o v e rn ig h t.
A fte r th e p re v io u s ly d e sc rib e d w o rk u p , 0.68 g (4 .6 6 moles) of th e
deu teriu m labeled diol w ere o b tain ed (47% y ie ld ).
1'26
T he diol was th e n disso lv ed in p y rid in e a n d th e so lu tio n re flu x e d
g e n tly u n d e r a rg o n .
T h en 1.46 g (7.66 moles) of T sC l d isso lv ed in p y rid in e
w ere a d d e d dropw ise to th e s tir r in g so lu tio n . A fte r ad d itio n was com pleted,
th e re a ctio n was s tir r e d a t re flu x o v e rn ig h t.
A fte r w o rk u p , 0.48 g (3.35
moles) of th e d e sire d p ro d u c t w ere iso la ted (78% y ie ld ).
IR:
3024, 2927, 2903, 2839, 1437, 1160, 1036, 818, 852 cnT1 .
1H NMR:
2 .1 6 -2 .0 5 (m , 2H ), 2 .5 5 -2 .3 0 (m, 4H ), 5.80 ( b s , 2H ).
MS (E l):
M+ = 128, HO, 109, 95, 79 ( b a s e ) , 72, 68, 54, 39, 27.
P re p a ra tio n of ( c is ) - 2 ,2 ,5 ,5 -te tra d e u te ro p h th a lic a n h y d rid e , 1471.
B u tad ien e sulfohe (2 0 .0 g , 0.169 moles) was com bined w ith 50 ml of
deu teriu m oxide a n d a cata ly tic am ount of metallic sodium .
was
s tir r e d
under
d ichlorom ethane.
a rg o n
fo r
48
h o u rs
an d
th e n
T he solution
e x tra c te d
w ith
T he so lv en t was d rie d an d s trip p e d to y ield 19.0 g
(0.156 moles) of th e d e s ire d p ro d u c t (92% y ie ld ).
1H NMR in d ic a te d th a t
s u b s titu tio n was ach iev ed in h ig h y ield (> 95%).
T he d eu teriu m labeled b u ta d ie n e s u lfone (9 .1 g , 0.075 moles) was
disso lv ed in 8 ml of d r y x y len es a n d 5.24 g (0.053 moles) of maleic
a n h y rid e .
T he re a c tio n was re flu x e d a t 200° C fo r 0 .5 h r s an d th e n
allowed to cool to room te m p e ra tu re .
charcoal w ere a d d e d to th e so lu tio n .
70 ml of b e n ze n e an d I g of
T he solution was h e a te d to re flu x
fo r 10 m inutes a n d th e n filte re d to rem ove th e ch arco a l.
T he filte re d
solution was s lig h tly cooled a n d th e n h ex an e was slow ly ad d ed u n til a
p e r s is te n t cloudy solution rem ained.
A fte r f u r th e r cooling of th e so lu tio n ,
4.64 g of th e d e sire d p ro d u c t c ry s ta lliz e d o u t of th e so lu tio n .
MP = 98-102° C
1H NMR:
3.88 ( s , 2 H ), 6.78 ( s , 2H ).
127
MS (E l):
128 (-C O ), 83, 68, 53, 41.
P re p a ra tio n of ( c is ) - 2 , 2 , 5 , 5 -te tra d e iite ro -8 -o x a b ic v c lo T4 .3 .0 ] n o n -3 - e n e , [431.
T he d eu teriu m labeled p h th a lic a n h y d rid e (2.62 g , 0.0170 moles) was
disso lv ed in 25 ml of THF an d ad d ed dropw ise to a so lu tio n of 0.66 g
(0.0174 moles) of LAH in 20 ml of THF a t 0° C .
T he re a c tio n was warmed
to room te m p e ra tu re a n d s tir r e d u n d e r a rg o n o v e rn ig h t. ' A fte r w o rk u p ,
2.18 g (0.0149 moles) of th e d e sire d p ro d u c t, as d eterm in ed b y IR , w ere
iso lated (88% y ie ld ).
T he diol was th e n disso lv ed in 25 ml of p y rid in e to h e ate d to a
g en tle re flu x u n d e r a rg o n .
T h en 3.13 g (0.0164 moles) of T sC l d isso lv ed in
25 ml of p y rid in e w ere ad d ed dropw ise to th e s tir r i n g so lu tio n .
re a c tio n was s tir r e d a t re flu x o v e rn ig h t.
T he
A fte r w o rk u p , 1.6 0 g (0.0125
moles) of th e d e sire d p ro d u c t w ere iso la ted (76% y ie ld ).
IR:
3024, 2968, 2925, 2857, 1058, 1056, 965, 923, 864, 807 cm"1 .
H NMR:
2.32 ( b s , 2H ), 3.65 (d d , 2H ), 3.89 (d d , 2H ), 5.65 ( s , 2H ).
MS (E l):
M+ = 128, HO, 109, 96, 93, 84, 82, 69 ( b a s e ) , 56, 41, 29.
P re p a ra tio n o f ( c is )-2 ,2 ,5 ,5 ,7 ,7 ,9 ,9 - o c ta d e u te ro -8 -o x a b ic y c lo [ 4 .3 .0 ]n o n -3 -e n e ,
1441.
T he d eu teriu m lab elled p h th a lic a n h y d rid e , [4 7 ], (2.02 g , 0.0129 moles)
was d isso lv ed in THF a n d ad d ed to a s tir r i n g solution of 0.77 g (0.0184
moles) of LAD in 20 ml of THF a t 0° C.
T he re a ctio n was warmed to room
te m p e ra tu re a n d th e n s tir r e d u n d e r a rg o n a t 0° C.
A fte r w o rk u p , 1.30 g ,
(8.55 moles) of th e d eu teriu m lab elled diol, a s d eterm in ed b y IR , w ere
iso lated (66% y ie ld ).
T he diol was th e n disso lv ed in d r y p y rid in e a n d h e a te d to re flu x
u n d e r a rg o n .
T h e n 1.79 g (9.41 moles) of T sC l d isso lv ed in p y rid in e w ere
128
ad d ed dropw ise to th e s tir r i n g so lu tio n .
o v e rn ig h t.
T he re a ctio n was s tir r e d a t re flu x
A fte r w o rk u p , 0.67 g (5 .1 0 moles) of th e d e sire d p ro d u c t w ere
iso lated (60% y ie ld ).
IR:
3023, 2926, 2192, 2088, 1778, 1304, 1208, 1183, 1143, 1119, 1096, 1083,
1067, 1059, 1036, 1000, 922 cm"1 .
"lH NMR:
2.30 ( s , 2H ), 5.62 ( s , 2H ).
MS (E l):
M+ = 132, 112, 98, 95, 87, 83, 82, 80, 72 ( b a s e ) , 69, 58, 52, 44,
41, 29.
129
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