Ready; Catalysis
Isomerization/cyclization-1
Olefin insertion into Metal alkyl can be followed by hydride elimination or additional olefin insertions:
R
R'
R'
R
R
M
-dimerization/oligomerization
-small molecules
MH
M
H
R'
R
H
M
R'
-polymerization
R'
Recall:
M
M
H
H
electron rich M (late transition metal) Keq < 1 ->dimerization, etc
electron poor M (early transition metal) Keq > 1 ->polymerization
Ready; Catalysis
Isomerization/cyclization-2
Shell Higher Olefin Process (SHOP)
Terminal Olefin
1-Hexene
1-Heptene
1-Octene
1-Nonene
1-Decene
1-Undecene
-SHOP process operates on 1 MILLION TON scale
-One of the largest applications of homogeneous transition metal catalysis
-Explains Adrich prices:
O
O
Ni
P
Ph2
H
S/C = 6000/1
n
C4-C8
+
>C20
Price (100mL)
$13
191
23
720
19
640
Isomerization
Catalyst
C4-C8
C10-C18
>C20
MoO3/Al2O3
(Olefin Metathesis)
m
n
Mixture of short
and long internal olefins
41%
40%
19%
sold (recall
hydroformylation)
C7-C14
C1-C3
Chauvin, Schrock, Grubbs: 2005 nobel prize in chemistry. For a history, see;
http://nobelprize.org/chemistry/laureates/2005/chemadv05.pdf
C7-C14
C1-C3
HCo(CO)4
H2/CO
Isomerization
Hydroformylation
Hydrogenation
HO
C10-C18
See CHNF, Capter 11, p593
Ready; Catalysis
Isomerization/cyclization-3
Ph
O
O
Ph
O
O
O
Ni
Ni
O
H
Ni
P
Ph2
P
PPh3
Ph2
O
O
P
P
Ph2 Ph2
Pre-catalyst
Catalytically inactive:
Catalyst death
J Mol Cat, 1987, 123
O
O
H
n
only linear products
are formed
Ni
P
H
Ph2
Migratory insertion
ethylene association
associative
displacement
O
O
O
Ni
P
Ph2
H
n
H
Ni
P
Ph2
"-Hydride
elimination
Relative rate of insertion vs
elimination/displacement
balanced to give low mw olefins
H
O
O
H
n
O
H
Ni
P
Ph2
!-complex
Ready; Catalysis
Isomerization/cyclization-4
Ligand change gives polymer insead of oligomer
note Ziegler-Natta catalysts (TiCl3/AlCl3) and cationic
metallocene catalysts not able to incorporate polar
monomers. Late TM = functional group tolerant
+
O
Ph
Ni
PPh3
N
i-Pr
1
1
n
i-Pr
m
HO
n
3.7 x 106g PE/mol Ni/Hr MW > 250,000
linear polyethylene
!-Hydride elim
ethylene association
H
HO
O
mw = >73,000
termination
Ni
H
n
H
Psycho-big ligand destabilizes 5-coordinate
intermediate en route to termination
N
O
H
Ni
H
N
O
Ni
ethylene association
N
polymer
Grubbs, Science, 2000, (287) 460
Ready; Catalysis
Isomerization/cyclization-5
Cl
Ni-Catalyzed Dimerization
aka hydrovinylation
catalyst activation
Cl
Ni
Ni
1/2
Cl
Ni
Ni
Cl
P(iPr)2(tBu), EtAlCl 2
Cl
PR3
Ni
major product
Cl---AlCl2Et
EtAlCl2
Cl---AlCl2Et
Ni
PR3
Ni
PR3
PR3
H
H
H
Cl---AlCl2Et
Ni
Cl---AlCl2Et
PR3
Ni
PR3
Cl---AlCl2Et
Ni
PR3
minor product
Catalytic cycle
Cl---AlCl2Et
rate = 60,000/sec at rt!!
Wilke, ACIEE, 1980, 622
ACIEE, 1988, 186
Historical account: ACIEE, 2003, 5000
Ni
PR3
Ready; Catalysis
Isomerization/cyclization-6
Enantioselective Hydrovinylation
common side products
Ethylene (1atm), [Ni(allyl)Cl]2
NaBAr4, CH2Cl2, low temp
+ oligomers
+
Ligand
Br
Br
Br
Ligand
Ph
O
O
(Ph-Me-5,3)2P
Ni
1 mol% Ni
98% y
>99% selectivity
89% ee
O
O
NHAc
OBn
1
Ph
0.04 mol% Ni
82% y
92% ee
O
P
little
N
~1%
<1%
O
2
Bulky ligand minimizes
styrene dimerization
Ph
O
Ni
3 steps
Br
Active olefin minimizes
ethlene polymerization
i-Bu
ibuprofen
OH
hydrovinylation of i-Bu-Styrene
with 1: 74% ee
w/ 2: 68% ee
1: Rajanbabu, JACS, 2001, 734
2: Leitner, JACS, 2001, 736
Ready; Catalysis
Isomerization/cyclization-7
Metal-mediated dimerization:
-common use
-mild conditions
-many applications
General Story:
Concerted
M
Mn+2
n
1 new C-C bond
2 new C-M bonds
stepwise
Mn+2
R3P
Ni
R3P
favored for e- rich PR3
Ni(COD)2 R P
3
PR3
Ni
Ni
w/ PPhEt2
Ni
-2 COD
w/P(OMe)3
Ni
PR3
favored for small e- poor PR3
Product distribution dependent on
nature of ligand and L/Ni.
PR3
Houk, JACS, 1994, 330
Weimann, ACIEE, 1980, 569
PR3
R3P
Ni
Ni
w/ P(OPh)3
favored for big e- poor PR3
Ready; Catalysis
Isomerization/cyclization-9
Metal-Catalyzed [4+4] cycloaddition
H
E
E
Ni(COD)2 (11 mol%)
PPh3 (33 mol%)
60 oC
E
E
+
E
E
H
70% (19:1 cis:trans)
2.6% (major product if P(tol)3 is used)
PR3
Ni
Ni
cis 5,5 system favored
E
E
H
E
Ni(COD)2 (11 mol%)
PPh3 (33 mol%)
60 oC
Ni
H
PPh3
H
H
85% y
20:1 cis:trans
99:1 d.r.
Trans 6,5 system favored
Recall thermal [4+4] forbidden under Woodward-Hoffman rules
Wender JACS, 1986, 4678; TL 1987, 2451
Ready; Catalysis
Isomerization/cyclization-10
Synthetic Applications of [4+4]
O
O
O
O
O
Ni(COD)2 (11 mol%)
PPh3 (33 mol%)
60 oC
Me
Me
67%
O
H
H
H
O
(+)-Asteriscanolide
Wender, Jacs, 1988, 5904
H
Ni(COD)2 (11 mol%) PO
PPh3 (33 mol%)
PO
110 oC
AcO
52%
O
OH
Ni(COD)2 (11 mol%)
PPh3 (33 mol%)
RO
110 oC
92%
H
E
H
O
OH OBz
Taxol
E
But in the end...
O
O
O
O
O
Ni(0): Wender, TL, 1987, 2221
Taxol syn: Wender, JACS, 1997, 2755, 2757
DABCO (cat)
HO
OH
O
OP
Ready; Catalysis
OP
Isomerization/cyclization-11
Catalytic [4+2] Cycloadditions
R
R'
Ni(COD)2 (10 mol%)
P(O-Biphenyl)3 (30 mol%)
X
H
H or CH2OP
R
1:1 - 2:1
n
alkynes poor dienophiles for
thermal diels-alder
X
Me, TMS
R'
O, NTs, NBoc, CH2
n
1 or 2
Ni
Wender Jacs 1989, 6432
jacs 1995, 1843
Ni(0)
Ni
OTBS
OTBS
H
Ni(COD)2 (10 mol%)
P(O-Biphenyl)3 (30 mol%)
97%
[Rh(COD)Cl]2 (5 mol%)
P(O-Biphenyl)3 (48 mol%)
90%
Ni(0) may prefer the less hindered olefin while Rh(I) prefers the more e- rich olefin
H
OTBS
Ready; Catalysis
Isomerization/cyclization-12
Ready; Catalysis
Isomerization/cyclization
Ni(cod)2 (20 mol%)
PR3 (40 mol%) (mostly PAr3)
O
+
+
H
Ar
Et3SiOTf
OSiEt3
+
Et3N HOTf
Ar
Et3N
O
R
H
Ar
Et3SiOTf
Ni(cod)2 (20 mol%)
Et3N, tol, rt
PCy2Ph (40 mol%)
(big, e- rich)
P(OEt)Ph2 (40 mol%)
(small, e- poor)
cf.
R
H/M
+ O
OSiEt3
R'
Ar
OTES
OTES
C5H11
Ph
85%
95:5 homoallyl:allyl
75:25 E/Z
C5H11
OTES
Ph
75%, 71:29 E/Z
M
O
+
Ar
OTES
O
O
H3C
64%
95:5
78:22 E/Z
cf. R
OSiEt
R
OTES
N
82%
84:16 allyl:homoallyl
60%
83:17
Jamison, JACS, 2006, 11513
Ph
Ready; Catalysis
Isomerization/cyclization
Dissociation
required for
good alignment
Favored with big P,
Small substrates
Ready; Catalysis
Intercepted hydrogenation
Ready; Catalysis
Isomerization/cyclization-13
[5+2] Cycloaddition
E
alkenes/alkynes
RhCl(PPh3)3 (0.1 mol%-0.5 mol%)
AgOTf (0.1 mol%- 0.5 mol%)
110 oC
R
X
H
83%
allenes
H
R = Me, 83%
TMS, 83%
CO2Me, 74%
t-Bu
E
E
H
H
RhCl(PPh3)3 (0.1 mol%-0.5 mol%)
X
E
E
X
110 oC
R
Me
R
R'
R'
X
O
E
H
R'
H
Me
not clear if ring expansion or cyclization occurs first
96%
92%
RhIII
X
RhIII
X
or
X
Rh
X
Ready; Catalysis
X
Wender, Jacs 1995, 4720; 1998, 1998,
10976; 1940; 1999, 5348
Isomerization/cyclization-14
Ready; Catalysis
Isomerization/cyclization
Metal-mediated trimerization:
Key early discoveries: Vollhardt, ACIEE, 1984, 539
H
Ph
CpCo(CO) 2
+
CoIII
[4+2]/retro [4+1]
or
insertion/R.E.
Ph
Ph
48%
Volhardt, Bergman
JACS, 1974, 4996
Ph
H
Proposed Mechanism
Rovis, JACS, 2006, 12370
Ready; Catalysis
Isomerization/cyclization-15
Ru-Catalyzed enyne isomerization
R
R'
+
CpRu(COD)Cl (cat)
+
R'
R
Can tune b:l (better for b-selective)
Trost, JACS, 1995, 615; JACS, 2001, 12504
R
R'
Intramolecular version:
X = O, NTs, C(ewg)2
X
PhO2S
[CpRu(CH3CN)3]PF6
R
n
n = 1,2
R'
82%
E
80%
Ph
n
R
E
PhO2S
R
X
R
R'
O
N
Ts 75%
62% (8:1)
Rxns also referred to as Alder-ene or metallo-ene reactions, but that is misleading given the most likely mechanism:
oxidative cyclization
X
R
RuIV
X
!-Hydride
elim.
X
RuIVH
R.E.
H
X
R
H
R
RuII
Trost, jacs 1995, 615; 2000,
714
Ready; Catalysis
Isomerization/cyclization-16
Synthetic Examples:
O
O
Cp*Ru(CH3CN)3PF6
O
o
(10 mol%) 50 C
O
+
46%, 3.5:1 branched:linear
5 equiv)
OFmoc
O
OFmoc
O
O
O
O
O
O
L
Ru
Linear
R
L
Ru
R
Branched
RO
Bulky L (eg. Cp*) disfavors linear product
O
O
O
HO
O
O
1.CpRu(CH3CN)3PF6
(10 mol%) 0.001M
58% y
2. acid
61% y
O
HO
O
O
O
O
HO
OH
proposed structure of amphidinolide A
Trost, JACS, 2002, 12421
Ready; Catalysis
Isomerization/cyclization-16
Similar mechanism observed with Ti(II)...
E
Cp2Ti(CO)2
(10 mol%)
E
E
E
note thorpe-engold effect common
Only with E olefins
E
E
TiCp2
E
H
both CO's gone
89% 1 isomer
E
20 mol% Cp2Ti(CO)2
E
Buchwald,
JACS, 1999, 1976
E
[4+2] substrate with Ni(0)
...and Rh(I)
O
CH3
CH3
H3C
[Rh(COD)Cl]2
(S)-BINAP
(±)- O
O
H3C
+ O
CH3
OH
O
only with Z olefins
O
40%
>99% ee
O
OH
46%
>99% ee
Zhang, TL, 2005, 1823
Ready; Catalysis
Isomerization/cyclization
General mechanism with electron rich transition metals:
Catalytic Pauson-Khand type reactions (reveiw: ACIEE, 2003, 1800)
EtOOC
EtOOC
[Cp2Ti(CO) 2] (5 mol%)
1.2 atm CO
EtOOC
TiIVCp2
EtOOC
EtOOC
O
EtOOC
91%
Buchwald, JACS, 1999, 5881
"
Ru3(CO)12 (2 mol %)
CO (10 atm)
EtOOC
EtOOC
[RhCl(CO)2]2 (5 mol %)
CO2Et
CO (0.1 atm)
Ph
Ready; Catalysis
[RuIICO]
EtOOC
"
86%
Murai, JOC, 1997, 3762
EtOOC
[RhIII]
EtOOC
CO2Et
TolBINAP (20 mol%)
[Ir(cod)2Cl]2
CO (1atm)
O
EtOOC
O
[IrIII]
Ph
Isomerization/cyclization
EtOOC
O
EtOOC
CO2Et
91%
JOMC, 2001, 624, 73
O
Ph
Shibata
JACS, 2000, 9852
O
Ready; Catalysis
Isomerization/cyclization-17
O
NR2
NR2
NEt2
Starting Materials:
LiNEt2/HNEt2
+
or
geranylamine
NEt2
3
1
NEt2
NEt2
2
4
NEt2
LiNEt2/HNEt2
Nerylamine
NEt2
Isomerization/Rxns
NEt2
Catalyst
Substrate
4 (100%)
CoH(N2)(PPh3)3
1
3 (85%); 4 (15%)
[Rh(PPh3)3(COD)]+
1
3 (100%)
1
3 (100%)
22
[Rh(R-BINAP)(COD)]+
1
S-3 (100%)
97
+
2
S-3 (100%)
96
+
[Rh(S-BINAP)(COD)]
NEt2
H+
H2/Ni
ZnBr2
OH
OH
menthol
ee(%)
1
[Rh(DIOP)(COD)]
NEt2
Products
Cp2TiCl2/iPrMgBr
CHO
Citronellal
isopulegol
Ready; Catalysis
Isomerization/cyclization-18
Process Development
Catalyst
Modification
Turnover number
Rh(BINAP)(COD)+
none
100
Rh(BINAP)(COD)+
added Red-Al
1,000
Rh(BINAP)(COD)+
Substrate purification
8.000
Rh(BINAP)2
catalyst recycling
400,000
Red-AL = Vitride = (MeOCH2CH2O)2AlH2 Na
compound
ee (%)
Production
(tons/yr)
CHO
use
synthetic intermediate
those stinky candles
97
1,500
98
10
insect growth regulator
100
1,000
pharmaceuticals
tabacco
houshold products
CHO
OMe
OH
Ready; Catalysis
Isomerization/cyclization
Mechanism
+
Rh(S-BINAP)
R
R
+
Me
NEt2
Me
D H
Rh(R-BINAP)+
NEt2
D
NEt2
Me
R2
N
P
S
P
H
P
R2
N
Rh
Rh
H
R
D
P
enamine
H D
ee determining
step
amine, S
R2
N
P
+
P
Rh
R 2N
Rh
P
P
H
Axial chirality results in gearing of Ph.
It is the location of the Ph's that gives a good
"chiral environment" near the metal
D
Rh
H
NH
R
Big group (R) in empty quadrant
empty
=
empty
Noyori, JACS, 1990, 4897
+