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11/03/2012
Allenes
Part 1. Introduction
A brief history
O
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
CHCOOH
"glutinic acid"
(Csp3) = 2.63
(Csp2) = 2.86
(Csp) = 2.96
cm-1
Me
Me
HOOC
Csp
R
HO
Met
Erel
[kcal/mol]
22.3
0.0
HO2C
nBu
H
Me
HO2C
nBu
H
Me
nBu
Me
mirror
CO2H
CO2H
Me
nBu
Hai Dao
11/03/2012
Allenes
Sigmatropic Rearrangements
[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
CO2Me
Me
[Rh]
R1
pentane
R2
OH
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
O
HO
O
Me
84%
kinetic cond.
64%
EtC(OEt)3
KOtBu
OH
R1
HO
OMOM
MeO2C
Rh2(S-DOSP)4
1mol%
OMOM
Me
C4H9
R2
quant.
H
.
OH
nBuLi
Me
OH
SnBu3
O
OMe
X Y
X
.
[3,3]
Y ZH
()-myltaylenol
O OH
Hai Dao
11/03/2012
Allenes
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
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
OH
+ H
Bu
syn
anti
n
n
n
syn: anti: Bu2CuLi = 60:40; Bu2CuLi.Me2S = 6:94; Bu2CuMgBr.Me2S = 1:99
OAc
(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
Hai Dao
11/03/2012
Allenes
1,2-Elimination
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.
R4
.
R2
TiCp2
R3
R1
Ph
up to 63% ee
R1
R4
Me R
OH
R1
PhCHO
R1
Cp2Ti(P(OEt)3)2
B(cat)
.
R2
R1
PdL*
50-80 oC
O Li
R2
Wittig-type Reaction
Pd(0)
SiMePhR*
Me
H
Ph
Ph
HR O
MeOH
R1
H
anti
R2
AH3
Olsson et al., J. Am. Chem. Soc. 1979, 7302.
Bn2N
()-sparteine
O
1,2-elimination
R2
Me
R4
OM
R1
R2
AlH3
2.tBuCO2H
R4
Y
OH
CO2Et
R3
R1
R2
N2
PPh3
CO2Et
PPh3
COCl
R2
R1
Et3N
CO2Et
.
R2
Hai Dao
11/03/2012
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)
1. nBuLi
Et2O:Hexane H
Cl
1. nBuLi
THF
.
Allenylmetal Compounds
H 2. Br(CH2)3Cl
2.C6H13CH2I H
88%
R2CHO
Ti(IV)/(S)-binaphthol
10 mol%
iPrSBEt
R1
CHO
CHO
R2
E, S
E 2'
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%
PivO
Me
Cy
OMe
.
Bpin
78%, d.r>95:5
InICl, AgP*
10 mol%
toluene, cpme
NHBoc
Me
MsOZn
transmetallation
fragmentation
OTf
R1
R2
NaNTMS2
CBr2
R1,
carbene approach
OTMS
E, SE2
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.
Hai Dao
11/03/2012
Allenes
thermal [2+2]
R2
125 oC
a: 31.2%
R1
. .
b: 62.5%
b, c
Me
2. CHD/ C6H5SH
h
46%
Ph
(R)
SOMO(*)
O
.
O
O
.
carbopalladation
H
R1
H
O
R2Pd(II)X
R
R1
PdX
complex
concave = major
73%, dr = 9:1
NAc
NAc
OR
LUMO
SOMO(*)
2. TMS3SiH, Et3B, O2
Br
O
. +
Br
Br
1. Bu3SnH, Et3B, O2
LUMO
Me
iPr
O
.
Me
biradical as intermediate
1. h/55 oC
CHD/NMC
photochemial [2+2]
R1
R2
Me
Me
OCOC6H4mCF3
iPr
disrot.
R2
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
Pd(OAc)2, PR3
back donation
2 most important orbital interaction in TM-alkyne
OH
Ph
HN
CO2Me
60%, 1:1
Me
CO2Me
Ph
.
TsN
PhI
Hai Dao
11/03/2012
Allenes
Pd(OAc)2, PR3
TsN
TsN
"In"
In, DMF, 80 oC
OH
93%
R1
Pd(0)/Pd(II)
PdHX
[Au]+
Ar
PdX
R1
ArB(OH)2
[Au]+
[Au]
[Au]+
carbene
bend
[Au]
allylic cation
Pd(II) 5mol%
Et3N
(HO)2B
+
Me
OMe
dioxane:H2O
80 oC
OH
Me
OMe
Ph
68%
Me
OMe
C1-C2: 1.340
C2-C3: 1.311
AuC1: 2.191
AuC2: 2.306
C1-C2-C3: 165.0
Hai Dao
11/03/2012
Allenes
.
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
PdX
Me
chiral counterion
interaction
R1
R1
Br
[Au]+
R2
R2Pd(II)X
- and attack
- attack is rare
A* .
Me
Me
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
[Au]
..
R1
R2
Br
O
R
O
E = COOMe
[Au]III
E
E
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
OTBS
O
CO
OPiv
Me
CO
Ru(CO)3
TsN
Me
R1
TsN
CO
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
[[M]
Hai Dao
11/03/2012
Allenes
DPS
OTBS
OTBS
iPr
Me
guanacasterpene A
Brummond and Gao et al., Org. Lett. 2003, 3491.
Allenes
Hai Dao
11/03/2012