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

Csp2 R

Csp2

Classification

dCH ()

1.061

1.086

dCC ()

1.309

1.337

IP

10.07 eV
10.64 eV

10.51 eV

EDG

EWG

IR: antisymetrical streching vibration 1950-1960

(vs. alkene: 1680 cm-1, alkyne 2200 cm-1)
1H NMR: = 4.9-4.4 ppm
13C NMR:
C, C = 120-73 ppm; C = 220-200 ppm.

CHCOOH

"glutinic acid"

(Csp3) = 2.63
(Csp2) = 2.86
(Csp) = 2.96

cm-1

revised structure (1954)

initial proposal (1887)

Brown, J. Chem. Phys. 1960, 1881.

The most simple allene vs. ethylene

Me

Me

HOOC

Csp
R

HO

Met

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

H
Me

HO2C

nBu

H
Me

nBu

Me

mirror

CO2H

CO2H

Me

nBu

Hai Dao
11/03/2012

Allenes

Baran Group Meeting

Sigmatropic Rearrangements

Part 2. Synthesis of Allenes

[2,3]

Prototropic Rearrangements

OMe

C4H9

N
H

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

.

CO2Me
Me

[Rh]
R1

pentane

R2

OH

Marshall et al., J. Org. Chem. 1991, 6264.

O

COPh

OH

Me

R2

CO2Me

tBu

OEt

Me
tBu

Me

EtCO2H

O
tBu

CO2Et

.
H

dr = 9:1, 68% ee

H
O

COPh
Newton et al., J. Chem. Soc., Perkin Trans 1, 1985, 1803.

Au(I)LOTf

Ar

NaBH4

Ar

HO
.

Ar

Shi et al., Org. Lett. 2011, 2618.

Toste et al., J. Am. Chem. Soc. 2004 15978.

HO
220
O
microwaves
.
oC

O
HO
O

LDA then NH4Cl

Me

Heathcock et al., J. Org. Chem. 1988, 4736.

84%

kinetic cond.
64%

EtC(OEt)3

KOtBu

OH

R1

HO

OMOM

MeO2C

Rh2(S-DOSP)4
1mol%

Davies et al., J. Am. Chem. Soc. 2012, 15497.

OMOM

Me

C4H9

R2

quant.

H
.

Marshall et al., J. Org. Chem. 1989, 5854.

N

OH

nBuLi

Me
OH

SnBu3
O

OMe

X Y

X
.

[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.

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Allenes

Baran Group Meeting

Nucleophilic Substitution

H
Nu

R1
.

anti SN2'

1
H R

Nu

R1

OH

LG

H
1
H R

RCuX.MgX.LiX

R Cu

LG

LG

R Cu

LG

R Cu

Me

R1
.

Pd(0)

1
R2 R

XPd

Me

nC

Me

6H13

F3C

96% ee

Me

Me

O H

OSO2Ar

TMSO

nC H
PhZnCl, THF F3C
6 13
77% yield, 96% ee

O
.

AgNO3
73%
R
H : PPh3, MeCN

kallolide B

isolaurallene precursor
Crimmins et al., J. Am. Chem. Soc. 2001,1533.

Ph

RO2C

Pd(PPh3)4
5 mol%

75%

Br

LiCuBr2

O
H

reduction

Pd(PPh3)4
CO, ROH

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

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

OAc

Oehlschlager and Czyzewska , Tetrahedron Lett. 1983, 5587.

(III) X

CuX
pdt

Me

OH

nBu

OH

1
H R

(III)

back donation:
dCu to CC
dCu to CLG

OH

.
H

1
H R

Cu species

H
OH

Marshall et al., J. Org. Chem. 1995, 796.

O

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Allenes

Baran Group Meeting

1,2-Elimination

Additions to Enynes Systems

R3

X
R

R1
R2

EWG

EWG

R
1. Me2CuLi.LiI

CO2Et

Me

R1
H

Li

Ph

O
HS

1. PhCHO
2. separation

SiMePhR*

Tf2O

Me

OH

TASF

Ph

SiMe3

Br

dr = 7:3

1. tBuLi
2. R1COR2

Me3Si

(cat)B
R

(S)-MeO-MOP
O
BH
O

(cat)B

PdL*

R1

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

R1

PhCHO

R1

Cp2Ti(P(OEt)3)2

B(cat)
.

R2

Takeda, Synthesis 2006, 2577.

R1

PdL*

50-80 oC

O Li
R2

Wittig-type Reaction
Pd(0)

50% yield, 18% ee

SiMePhR*

Oestreich and Hoppe, Tetrahedron Lett. 1999, 1881.

Me

H
Ph

Ph
HR O

McGarvey, Tetrahedron Lett. 1988, 1355.

MeOH

R1
H

anti
R2
AH3
Olsson et al., J. Am. Chem. Soc. 1979, 7302.

Bn2N

()-sparteine
O

1,2-elimination
R2

Me

Krause, Liebigs Ann. Chem. 1996, 1487.

nBuLi

R4

OM
R1

R2

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

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

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

CHO

CHO

R2

E, S

E 2'

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

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%

Lawrence et al., J. Am. Chem. Soc. 2012, 12970.

PivO

Me

Cy

OMe

.
Bpin

78%, d.r>95:5

Marshall et al., Org. Lett. 2005, 1593.

InICl, AgP*
10 mol%
toluene, cpme

NHBoc

Me

MsOZn

transmetallation

fragmentation
OTf

R1

R2

NaNTMS2

CBr2

R1,

carbene approach

OTMS

E, SE2

Finn et al., J. Am. Chem. Soc. 1997, 3429.

Me

R2

R2

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

R1

98%

NHCbz
.
Cy

75%, 88% ee

NHCbz

Cy

18%, 25% ee

Kobayashi and Schneider et al., Angew. Chem. Int. Ed. 2011, 11121.

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Allenes

Baran Group Meeting

Cycloadditions

Free Radical Addition

thermal [2+2]
R2

125 oC

a: 31.2%

R1

. .

b: 62.5%

b, c

Me

2. CHD/ C6H5SH
h
46%

CHD: 1,4 cyclohexadiene

NMC: N-methylcarbazole

Ph

(R)

SOMO(*)
O

.
O

O
.

carbopalladation

H
R1
H
O

R2Pd(II)X

R
R1
PdX

complex

Weisner, Tetrahedron 1975, 1655.

Nauguier and Renaud et al., Tetrahedron asymmetry 2003, 3005.

concave = major

73%, dr = 9:1

NAc

NAc

Palladium-catalyzed Addition to Allenes

Becker et al., Chem. Commun. 1975, 277.

OR

LUMO

SOMO(*)

2. TMS3SiH, Et3B, O2

Br

O
. +

Br

Br

1. Bu3SnH, Et3B, O2

LUMO

Me

iPr

Mayers et al., J. Am. Chem. Soc. 1993, 7926.

O

O
.

Me

biradical as intermediate

1. h/55 oC
CHD/NMC

photochemial [2+2]

R1

R2

Me

Me

OCOC6H4mCF3
iPr

disrot.

R2

in general, it is thermodynamic control

Me

disrot.
a

c: 6.3%

conrotatory

R1

Nu

R
R1

Nu

RN

I
N
Ts

N
H

+
OH

K2CO3, PhMe
110 oC

N
Ts
Grigg, Chem. Commun. 2001, 964.

O
O

interaction

PdX

PhMe
45 oC

Me

Ph

Pd(0)
CO, K2CO3

Carbophylic Activation by Solf Lewis Acids

Pd(OAc)2, PR3

back donation
2 most important orbital interaction in TM-alkyne

OH

Ph
HN

CO2Me

60%, 1:1

Me

CO2Me

Grigg, Tetrahedron Lett. 2000, 7129.

Ph

Ph
.

TsN

PhI

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Allenes

Baran Group Meeting

Pd(OAc)2, PR3

TsN

TsN

"In"

In, DMF, 80 oC

OH

Rayon and Frenking et al., J. Phy. Chem. A 2004, 3134.

calculated data (CuI, AgI, AuI):

- ethylene ligand is slightly stronger bonded to TM+
- interaction contributed to about 55-70%, 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 2 mode,
additions of arylboronic acid to allenes
- allenes have 2 and several 1 modes
.
R1

R1

Pd(0)/Pd(II)

PdHX

[Au]+

Ar

PdX

R1

ArB(OH)2

[Au]+

[Au]

[Au]+

carbene

bend

(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
C2-C3: 1.311
AuC1: 2.191
AuC2: 2.306
C1-C2-C3: 165.0

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Allenes

Baran Group Meeting

.
Me

dppm(AuCl)2

[TM]+

Nu

vs.

Br

PhMe, rt

91%, 97%ee

Ph
OH
Ph

complex

Ph

AgOTf

[Ag]
.

Ph

AuIIICl3

Ph

HO

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

[Au]+

R2

R2Pd(II)X

- and attack
- attack is rare

A* .
Me

Me

Widenhoefer et al., Organometalic 2010,4207.

O
O P
O
O

AgA*

face exchange
conclusions:
- gold tends to bind to less substituted C=C
- fluxional behavior: -face exchange via 1 intermediate

HO

HO

OH

AuCl3

OH
Ph

[Au]

O
H

PhMe, rt

Kim and Lee et al., Adv. Synth. Catal. 2008, 547.

[Au]

..
R1

R2

Br
O

R
O

E = COOMe

[Au]III

E
E

Gevorgyan et al., J. Am. Chem. Soc. 2008, 6940.

Me

LAuCl
AgSbF6

[Au]III

Br
H

R
H

Br

[Au]I

L = P(2,3-tBu2C6H3O)3
L = P(tBu2(o-biphenyl))3
alkyl migration

99:1 (91%)
4:96 (89%)
H shift

Me

HO

(PhO)3PAuCl/AgOTf
(5 mol%)
DCM, rt

H
O
O

LAu
O H
Me
Me

E
E

55%
Widenhoefer et al., J. Am. Chem. Soc. 2006, 9066.

LAu
H

LAu
H

[2+4]
[3C+4C]

exo like TS

H
H
Toste et al., J. Am. Chem. Soc. 2009, 6348.
Montserrat et al., J. Am. Chem. Soc. 2009, 13020.

O
R1

N
R

[M]

O
R2

[M]
R1

N
R

R2

Phosphine-catalyzed Cycloaddition

+
O

EtO2C

(-)-geniposide

63%
EtO2C

OPiv
O

OEt

R3

PH2R3

R1
.

PH2R3

OPiv

R3

[M]
R3

exo

+
R1

R1

R2
R3

iPr

DPS

[Rh(CO)2Cl]2
10 mol%
80 oC

PhMe,
65%

R2

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

R2

DPS: dimethylphenylsilyl

R1

R2

R3

Me

TsN
R

R1

OTBS
OEt

(CO)3
Ru Me

allenic Pauson-Khand reactions

OTBS
O

CO

OPiv

Me

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

Pt cat. favors carbenoid mechanism vs. Au cat. via carbocationic intermediate

PPh3 (10 mol%)

PhMe, 110 oC

Ru(CO)4

R1

[M]

R1

Ru(CO)4
H
TsN

[M]

N
R

N
R

[M] = PtCl2, CO

carbonylation

[M] = Au(I)
R2

R2

NHTs

N
R

R2

O
N
R

R2
R1

Carbonylation and Pauson-Khand Reaction

[[M]

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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