Hai Dao
11/03/2012
Allenes
Baran Group Meeting
Part 1. Introduction
A brief history
O
1828: Synthesis of urea = the starting point of modern organic chemistry.
1875: Prediction of the correct structure, Van't Hoff, La Chimie dans I'Espace, Bazendijk, P.M., Rotterdam 1875, 29.
1887: First synthesis of an allene (glutinic acid), Burton and Pechmann, Chem. Ber. 1887, 145.
Confirmation of the structure of "glutinic acid", Jones et al., J. Chem. Soc. 1954, 3208.
1924: Isolation and characterization of first natural allene, pyrethrolone, Staudinger and Ruzicka, Helv. Chim. Acta 1924, 177.
1928: First review on allenes, Bouis, Ann. Chim. (Paris) 1928, 402.
1935: Synthesis of first chiral allene, Maitland and Mills, Nature 1935, 994.
Last decade (2002-2012): Shengming Ma (148 publications); Norbert Krause (42 publications), Benito Alcaide and Pedro
Almendros (33 publications). Scifinder, key word: allenes. Google gave 184000 (vs. alkyne 999000) (Nov 2012).
Structure and physical properties
pyrethrolone
HOOCHC
COOH
R
R
α
.
Csp2 R
Csp2
Classification
.
H
H
H
H
H
H
dC−H (Å)
1.061
1.086
dC−C (Å)
1.309
1.337
IP
10.07 eV
10.64 eV
10.51 eV
.
EDG
EWG
R
IR: antisymetrical streching vibration 1950-1960
(vs. alkene: 1680 cm-1, alkyne 2200 cm-1)
1H NMR:δ = 4.9-4.4 ppm
13C NMR: δ
Cα, Cγ = 120-73 ppm; δCβ = 220-200 ppm.
H
CHCOOH
"glutinic acid"
χ(Csp3) = 2.63
χ(Csp2) = 2.86
χ(Csp) = 2.96
cm-1
H
.
revised structure (1954)
initial proposal (1887)
Brown, J. Chem. Phys. 1960, 1881.
The most simple allene vs. ethylene
Me
Me
HOOC
Csp
R
γ
β
.
HO
.
δ−
.
δ+
Met
δ−
.
δ−
δ−
R = alkyl, alkenyl, aryl, alkynyl
EWG = CO2R,CN, SO2R...
EDG = OR, SR, NR2, Hal, ...
Met = Li, Mg, B, Si, Sn, Zn, In, Ti, Cu, Pd
Erel
[kcal/mol]
22.3
- allenes can react as both nucleophiles and electrophiles
- changing the substitutes can alter the reactivity preferences
Determination the configuration of chiral allenes
.
2.1
0.0
isomers of smallest allene and
their relative energies
many substituted allenes are thermodynamically more stable than
the corresponding alkynes.
HO2C
nBu
R
H
Me
HO2C
.
nBu
H
Me
R
H
.
nBu
Me
mirror
CO2H
S
H
CO2H
Me
nBu
S
Hai Dao
11/03/2012
Allenes
Baran Group Meeting
Sigmatropic Rearrangements
Part 2. Synthesis of Allenes
[2,3]
X
Prototropic Rearrangements
Y
Y
X
.
Z
.
OMe
H
C4H9
N
H
N
KOH, K2CO3
OH
PhMe, reflux
68%
H
R1
Me
Et3N
71%, 93%ee
[2,3]-Wittig Rearr.
N2
Hoffmann et al., Helv. Chim. Acta 2000, 777
.
O
O
CO2Me
Me
+
[Rh]
R1
pentane
R2
OH
Marshall et al., J. Org. Chem. 1991, 6264.
O
O
COPh
OH
Me
R2
CO2Me
tBu
OEt
Me
tBu
Me
EtCO2H
O
tBu
E
CO2Et
.
H
H
dr = 9:1, 68% ee
O
.
H
O
COPh
Newton et al., J. Chem. Soc., Perkin Trans 1, 1985, 1803.
Au(I)LOTf
Ar
NaBH4
.
Ar
HO
.
Ar
.
R
R
Shi et al., Org. Lett. 2011, 2618.
Toste et al., J. Am. Chem. Soc. 2004 15978.
HO
220
O
microwaves
.
oC
O
HO
O
H
O
R
LDA then NH4Cl
O
Me
.
Heathcock et al., J. Org. Chem. 1988, 4736.
84%
kinetic cond.
64%
EtC(OEt)3
O
O
KOtBu
O
OH
R1
HO
OMOM
O
MeO2C
Rh2(S-DOSP)4
1mol%
Davies et al., J. Am. Chem. Soc. 2012, 15497.
OMOM
O
Me
C4H9
R2
quant.
O
H
.
Marshall et al., J. Org. Chem. 1989, 5854.
N
N
OH
nBuLi
Me
OH
.
SnBu3
O
OMe
X Y
X
.
H
[3,3]
Y ZH
(−)-myltaylenol
Winterfeldt et al., Chem. Eur. J. . 1998, 1480.
O OH
98%, dr > 98%
Barriault et al., Org. Lett. 2002, 1371.
Hai Dao
11/03/2012
Allenes
Baran Group Meeting
Nucleophilic Substitution
H
Nu
R1
.
anti SN2'
H
1
H R
Nu
R1
H
OH
LG
H
1
H R
RCuX.MgX.LiX
R Cu
LG
LG
R Cu
LG
H
H
R Cu
Me
R1
.
Pd(0)
H
1
R2 R
XPd
X
Me
nC
Me
6H13
F3C
.
96% ee
Me
Me
.
O H
.
OSO2Ar
TMSO
O
H
.
nC H
PhZnCl, THF F3C
6 13
77% yield, 96% ee
O
.
AgNO3
73%
R
H : PPh3, MeCN
kallolide B
O
isolaurallene precursor
Crimmins et al., J. Am. Chem. Soc. 2001,1533.
Ph
H
RO2C
H
H
Pd(PPh3)4
5 mol%
75%
Br
H
LiCuBr2
O
O
H
reduction
Pd(PPh3)4
CO, ROH
.
H
O
carbonylation
R2
Kono and Yamanaka et al., Chem. Lett. 2000, 1360.
Me
Me
Me
Fallis et al., Angew. Chem. Int. Ed. 2008,568. MsO
TMSO
.
Me
OAc
O H
coupling
R1
allylpalladium species
.
Me
Me
AcO
n
H
MsO
THF, 0 oC, 3.5 h
15 min 0 oC
85%
OH
Cu-promoted racemization of allenes through SET
Me2S stablizes Cu species
mechanism of organocopper-mediated stereospecific substitution
MeMgBr (30 equiv)
OAc LiBr (30 equiv)
CuI (30 equiv)
+ H
Bu
syn
anti
n
n
n
syn: anti: Bu2CuLi = 60:40; Bu2CuLi.Me2S = 6:94; Bu2CuMgBr.Me2S = 1:99
H
OAc
.
Oehlschlager and Czyzewska , Tetrahedron Lett. 1983, 5587.
(III) X
CuX
pdt
Me
OH
nBu
OH
1
H R
X
(III)
back donation:
dCu to π∗C−C
dCu to σ∗C−LG
OH
.
H
1
H R
X
Cu species
O
H
OH
Marshall et al., J. Org. Chem. 1995, 796.
O
Hai Dao
11/03/2012
Allenes
Baran Group Meeting
1,2-Elimination
Additions to Enynes Systems
R3
X
R
.
R1
R2
EWG
EWG
R
.
H
R
1. Me2CuLi.LiI
R
n
R
CO2Et
.
Me
R1
H
Li
Ph
O
HS
N
1. PhCHO
2. separation
SiMePhR*
Tf2O
Me
OH
TASF
Ph
O
SiMe3
N
R
Br
O
dr = 7:3
1. tBuLi
2. R1COR2
Me3Si
R
R
(cat)B
R
(S)-MeO-MOP
O
BH
O
(cat)B
PdL*
R
R1
H
R3
Cl
R2
Me
R2
Cl
CO2Et Fe cat.
Hayashi, J. Chem. Soc., Chem. Commun 1993, 1468.
.
R4
.
R2
TiCp2
R3
R1
Ph
up to 63% ee
R1
R4
Takeda, Org. Biomol. Chem., 2005, 2914.
Me R
OH
O
R1
PhCHO
H
.
R1
Cp2Ti(P(OEt)3)2
B(cat)
.
R2
R
Takeda, Synthesis 2006, 2577.
R1
PdL*
H
50-80 oC
O Li
R2
Wittig-type Reaction
Pd(0)
.
50% yield, 18% ee
SiMePhR*
Oestreich and Hoppe, Tetrahedron Lett. 1999, 1881.
R
Me
H
Ph
O
Ph
HR O
.
McGarvey, Tetrahedron Lett. 1988, 1355.
.
MeOH
H
R1
H
anti
R2
AH3
Olsson et al., J. Am. Chem. Soc. 1979, 7302.
Bn2N
(−)-sparteine
O
1,2-elimination
R2
H
Me
Krause, Liebigs Ann. Chem. 1996, 1487.
nBuLi
R4
H
OM
R1
R2
R
R = tBu, n = 1, 90% (1,8 addition); R = Me, n = 2, 68% (1,10 addtion);
R = Me, n = 3, 26% (1,12 addtion)
NBn2
AlH3
n
2.tBuCO2H
R4
.
Y
OH
CO2Et
R3
R1
R2
N2
PPh3
CO2Et
PPh3
COCl
R2
R1
Et3N
CO2Et
.
R2
Dai et al., J. Am. Chem. Soc. 2007, 1494.
Hai Dao
11/03/2012
Allenes
Baran Group Meeting
Part 3. Reactions of Allenes
Other Methods
NOT to be covered:
- allenes as an alkenes (eg: Diels-Alder reaction, coupling)
- allenes as enones, unsaturated esters...(eg. 1,4-addition inEWG substituted
allenes)
allenyl and propargyl metal reagents
C6H13
1. nBuLi
Et2O:Hexane H
H
.
Cl
1. nBuLi
THF
.
Allenylmetal Compounds
H 2. Br(CH2)3Cl
2.C6H13CH2I H
88%
Hooz et al., Tetrahedron. Lett. 1985, 271.
Arseniyadis et al., Tetrahedron 1979, 353
SnnBu3
R2CHO
+
Ti(IV)/(S)-binaphthol
10 mol%
iPrSBEt
R1
n
CHO
O
n
CHO
E
R2
E, S
E 2'
E
General rule (can be altered depend on
and/or metals, electrophiles):
- allenic isomer is more table than propagylic one
- reaction in both SE2 (Li, Mg...) and SE2' (Sn, B, In, Zn...) manners
- syntheses: metal-halogen exchange/propargylic deprotonation (Li), Babier
type oxidative addition (Mg, Zn, In...), transmetallation (Li, Mg to Cu, Sn, B,
Si, Zn, Ti...), or palladium catalyzed hydrogenation (B, Si)
- some allenic and propargylic metals can be isolated (M=B, Si, Sn)
O
.
Pd(OAc)2.PPh3
Me
H
Me + H
PivO
OPiv
O
OMs
40-50%
NHBoc
OH
Me
Et2Zn, THF
Me
Pd(0)
MeLi
PivO
.
Br
.
[Pd]
Br
Thies et al., J. Org. Chem. 1975, 585.
NHCbz
TBAF
HO
Me
.
52%
H
O
Lawrence et al., J. Am. Chem. Soc. 2012, 12970.
PivO
H
.
Me
Cy
OMe
.
Bpin
78%, d.r>95:5
Marshall et al., Org. Lett. 2005, 1593.
InICl, AgP*
10 mol%
toluene, cpme
H
NHBoc
Me
MsOZn
transmetallation
fragmentation
OTf
R1
R2
NaNTMS2
CBr2
H
H
R1,
carbene approach
OTMS
E, SE2
E
Finn et al., J. Am. Chem. Soc. 1997, 3429.
Me
M
R2
.
R2
.
M
R1
n =2,4,6,8,10
TMSO
R1
R2
(iPrO)2TiCl2
O
R2
.
2 ,DCM
(Me2N)3P=CH2
[1,3]
R1
OH
titanium-phosphorus ylides
O
R1
E
98%
NHCbz
.
Cy
75%, 88% ee
NHCbz
+
Cy
18%, 25% ee
Kobayashi and Schneider et al., Angew. Chem. Int. Ed. 2011, 11121.
Hai Dao
11/03/2012
Allenes
Baran Group Meeting
Cycloadditions
Free Radical Addition
thermal [2+2]
R2
125 oC
a: 31.2%
R1
+
.
H
R
. .
b: 62.5%
α
.
b, c
Me
2. CHD/ C6H5SH
hν
46%
.
. δ−
hν
δ−
CHD: 1,4 cyclohexadiene
NMC: N-methylcarbazole
O
Ph
(R)
O
SOMO(π*)
O
O
.
O
O
.
hν
carbopalladation
δ−
.
H
R1
H
O
R2Pd(II)X
R
R1
PdX
π complex
O
δ−
Weisner, Tetrahedron 1975, 1655.
R
Nauguier and Renaud et al., Tetrahedron asymmetry 2003, 3005.
H
concave = major
R
73%, dr = 9:1
NAc
NAc
H
.
O
Palladium-catalyzed Addition to Allenes
Becker et al., Chem. Commun. 1975, 277.
.
OR
O
LUMO
SOMO(π*)
hν
O
2. TMS3SiH, Et3B, O2
Br
O
. δ+
δ−
O
Br
Br
1. Bu3SnH, Et3B, O2
LUMO
O
Me
O
O
H
iPr
Mayers et al., J. Am. Chem. Soc. 1993, 7926.
O
O
.
H
H
Me
H
biradical as intermediate
O
H
1. hν/55 oC
CHD/NMC
photochemial [2+2]
.
R1
R2
Me
H
Me
O
R
β
OCOC6H4mCF3
iPr
disrot.
R2
in general, it is thermodynamic control
Me
disrot.
a
β
.
H
c: 6.3%
conrotatory
R1
α
Nu−
R
R1
Nu
RN
.
I
N
Ts
N
H
+
OH
K2CO3, PhMe
110 oC
N
Ts
Grigg, Chem. Commun. 2001, 964.
N
O
O
σ−interaction
PdX
PhMe
45 oC
Me
Ph
R
Pd(0)
CO, K2CO3
.
I
Carbophylic Activation by Solf Lewis Acids
Pd(OAc)2, PR3
+
π−back donation
2 most important orbital interaction in TM-alkyne
O
OH
Ph
HN
CO2Me
60%, 1:1
Me
CO2Me
Grigg, Tetrahedron Lett. 2000, 7129.
Ph
Ph
.
TsN
PhI
+
Hai Dao
11/03/2012
Allenes
Baran Group Meeting
Pd(OAc)2, PR3
TsN
TsN
"In"
In, DMF, 80 oC
O
OH
O
Rayon and Frenking et al., J. Phy. Chem. A 2004, 3134.
calculated data (CuI, AgI, AuI):
- ethylene ligand is slightly stronger bonded to TM+
- σ−interaction contributed to about 55-70%, π−back donation contributed
to about 20-33% of covalent bonds.
that means:
- reactions at the alkyne (allenes) vs. olefin sites are kinetic in origin (steric?)
- TM interacted multiple bonds become more electrophilic
Furstner and Davies, Angew. Chem. Int. Ed. 2007, 3410.
93%
allenes vs. alkenes (and alkynes):
Kang et al., J. Org. Chem. 2002, 4376. - alkynes and alkenes coodinate to TM in η2 mode,
additions of arylboronic acid to allenes
- allenes have η2 and several η1 modes
.
R1
R1
Pd(0)/Pd(II)
PdHX
[Au]+
Ar
PdX
+
R1
.
ArB(OH)2
[Au]+
[Au]
[Au]+
carbene
bend
.
η2
(Pt, Rh give terminal olefin adducts)
[Au]
allylic cation
X-ray and NMR studies of first gold allenes complexes
OMe
OH
.
Ph
Pd(II) 5mol%
Et3N
(HO)2B
+
Me
OMe
dioxane:H2O
80 oC
OH
Me
OMe
Ph
68%
Me
OMe
Yoshida et al., Org. Lett. 2009, 1441.
C1-C2: 1.340 Å
C2-C3: 1.311 Å
Au−C1: 2.191 Å
Au−C2: 2.306 Å
C1-C2-C3: 165.0
Hai Dao
11/03/2012
Allenes
Baran Group Meeting
.
Me
dppm(AuCl)2
[TM]+
α
γ
.
β
Nu−
vs.
Br
R
O
PhMe, rt
H
R
91%, 97%ee
Ph
OH
Ph
π complex
Ph
AgOTf
[Ag]
.
Ph
AuIIICl3
Ph
HO
O
Br
.
R
R = 2,4,6-iPrC6H3
Me
Me
Halminton and Toste et al., Science 2007, 496.
PdX
TM = "cationic" Au, Pt, Ag, Pd
PEt3AuICl
Me
chiral counterion
interaction
R1
R1
Br
H
[Au]+
R2
R2Pd(II)X
.
- α and γ attack
- β attack is rare
A*− .
Me
Me
Widenhoefer et al., Organometalic 2010,4207.
O
O P
O
O−
O
AgA*
π−face exchange
conclusions:
- gold tends to bind to less substituted C=C
- fluxional behavior: π-face exchange via η1 intermediate
R
HO
HO
OH
AuCl3
OH
Ph
[Au]
O
H
PhMe, rt
R
O
Kim and Lee et al., Adv. Synth. Catal. 2008, 547.
O
[Au]
..
R1
O
R2
.
Br
O
H
R
O
O
H
+
E
E = COOMe
[Au]III
E
E
E
Gevorgyan et al., J. Am. Chem. Soc. 2008, 6940.
Me
LAuCl
AgSbF6
E
.
[Au]III
O
E
Br
H
R
H
R
H
.
Br
[Au]I
H
L = P(2,3-tBu2C6H3O)3
L = P(tBu2(o-biphenyl))3
alkyl migration
99:1 (91%)
4:96 (89%)
H shift
Me
HO
O
(PhO)3PAuCl/AgOTf
(5 mol%)
DCM, rt
H
O
O
LAu
O H
Me
Me
2π
O
.
E
E
55%
Widenhoefer et al., J. Am. Chem. Soc. 2006, 9066.
4π
LAu
H
LAu
H
[2π+4π]
[3C+4C]
E
E
exo like TS
E
E
H
H
Toste et al., J. Am. Chem. Soc. 2009, 6348.
Montserrat et al., J. Am. Chem. Soc. 2009, 13020.
O
O
R1
N
R
O
[M]
O
O
R2
.
[M]
R1
H
N
R
R
R2
Phosphine-catalyzed Cycloaddition
.
+
O
EtO2C
O
(-)-geniposide
O
63%
EtO2C
OPiv
O
H
H
OEt
R3
PH2R3
4π
R1
.
PH2R3
OPiv
R3
+
[M]
R3
exo
+
R1
R1
R2
R3
M
iPr
DPS
[Rh(CO)2Cl]2
10 mol%
80 oC
PhMe,
65%
O
R2
O
endo
general rules:
- Co2(CO)8 is not effective, causing polymerization
- Mo(CO)6 favors exo-cyclized products
- [Rh(CO)2Cl]2 favors endo-cyclized products
- R3 = H: endo products are prefered
.
R2
O
M
R2
DPS: dimethylphenylsilyl
2π
R1
R2
R3
Me
O
TsN
R
R1
OTBS
OEt
(CO)3
Ru Me
O
allenic Pauson-Khand reactions
OTBS
O
CO
R
OPiv
O
Me
R
CO
Ru(CO)3
TsN
Me
R1
General conclutions (noble metals catalyzed reactions of allenes,
alkynes):
- "importance of charge in synthetic design: introduction of a charged atom
into a molecular skeleton undergoing bond reorganization usually lowers the
activation of energy of the process, which leads to milder reaction conditons
and greater selectivities"
- effect of noble metals on TS: play important roles in various points of the
reaction ( not just as solf Lewis acids).
topics in current chemistry, 302, p125-6.
TsN
CO
.
R
Pt cat. favors carbenoid mechanism vs. Au cat. via carbocationic intermediate
PPh3 (10 mol%)
PhMe, 110 oC
Ru(CO)4
.
R1
[M]
R1
O
O
Ru(CO)4
H
TsN
O
[M]−
N
R
H
N
R
[M] = PtCl2, CO
O
carbonylation
+
[M] = Au(I)
R2
R2
NHTs
H
N
R
R2
O
N
R
O
R2
R1
O
Carbonylation and Pauson-Khand Reaction
O
[[M]
O
Hai Dao
11/03/2012
Allenes
Baran Group Meeting
DPS
OTBS
OTBS
iPr
Me
guanacasterpene A
Brummond and Gao et al., Org. Lett. 2003, 3491.
Baran Group Meeting
Allenes
Hai Dao
11/03/2012
other important topics: oxidation (including epoxidation), electrophilic additions...
Part 4. Important References
1. Modern allene chemistry, vol. 1 and 2; edited by Krause and Hashmi, Wiley-VCH, 2004.
2. Computational mechanism of Au and Pt catalyzed reactions, topics in current chemistry, 302, Soriano and Marco-Cotelles, Springer, 2011.
3. Allenes in organic synthesis, Schuster and Coppola, Wiley, 1984.
4. Recent development in allene chemistry, tetrahedron, 1984, 2805.
5. Allenes in catalytic asymmetric synthesis and natural product synthesis, Ma et al., Angew. Chem. Int. Ed. 2012, 3074.
6. Gold-catalyzed nucleophilic cyclization of functionalized allenes: a powerful access to carbo-heterocycle, Krause et al., Chem Rev. 2011, 111.
7. Catalytic carbophilic activation: catalysis by platinum and gold p acids, Furstner and Davies, Angew. Chem. Int. Ed. 2007, 3410.
8. how easy are the synthesis of allenes?, Ma et al., Chem. Commun. 2011, 5384