Post on 19-May-2019
Alkylation of Metalated O-Silyl Cyanohydrins of β-Silyl-α,β-epoxyaldehydes
Takeda, K.;Kawanishi, E.;Sasaki, M.;Takahasi, Y.;Yamaguchi, K. Org. Lett. 2002, 4, 1511-1514.
1
tBuMe2Si
O
CN
OSiMe2But
H
tBuMe2SiO CN
OSiMe2But
H
tBuMe2SiO CN
OSiMe2But
H
tBuMe2Si
O
CN
OSiMe2But
tBuMe2Si CN
OSiMe2ButO
H
RXbase
-80 °C5 min
R = Me, Et, Pri, CH2CH=CH2, CH2Ph
base
LiNiPr2 (LDA)
LiN(SiMe3)2 (LHMDS)
NaN(SiMe3)2 (NHMDS)
KN(SiMe3)2 (KHMDS)
yield (%)
58 - 98
15 - 90
80 - 98
80 - 95
tBuMe2SiO CN
OSiMe2But
H
R
A Proposed Reaction Pathway2
Sasaki, M.;Kawanishi, E;Nakai, Y.;Matsumoto, T.;Yamaguchi, K.;Takeda, K. J. Org. Chem. 2003, 68, 9330-9339.
OSiR3NC
HH
R3Si
O
CN
R3SiO
HH
R3Si
O
OSiR3NC
H
SiR3
OH
M
SiR3H
H
H
NC OSiR3
O
CNHR3SiO
HO
SiR3
NC
OSiR3
HO
SiR3
H
CNR3SiO
H
SiR3
OH
R3SiO CN
OSiR3
1A
CN
OSiR3R3SiO
CN
OSiR3R3SiO
R
CN
OSiR3
R3SiO
R
N
R R
SiR3
H
H
H
R3SiO CN
O
1B
N
R R
E-isomer
Z-isomer
An Approach to New Acrolein β-Anion Equivalent3
O
ZR3SiR3Si
O
Zbase
El+
Z
H
R3Si
O
El+
ZR3SiO
El
H
desilylationelimination
O El
H
Z = leaving group
O
ZR3Si
Acrolein !-Anion Equivalent
H
O
Equivalents of the Acrolein β-Anion Synthon
4
Corey, E. J.; Erickson, B. W.; Noyori, R. J. Am. Chem, Soc. 1971, 93, 1724-1729.Chinchilla, R.; Nájera, C. Chem. Rev. 2000, 100, 1891-1928.
RX YRn-BuLior LDA RX YR
Li RX YREl
El
1. hydrolysis2. elimination
El
H
O
H
O X = Y = S or Se
X = S, Y = O
X = SO2, Y = O
MeS SMe
1. LDA2. n-C5H11Br
-75 °C, 2hr(90%)
MeS SMe
C5H11
HgCl2
50 °C, 4 hr(84%)
C5H11
H
O
MeS SMe
1. LDA
2. R1R2CO
-75 °C to rt(89-97%)
MeS SMe
R2
R1 OH
HgCl2
85 °C, 4 hr(41%)
H
O
R1 = C2H5; R2 = H
R1 = R2 = CH3
R1 = R2 = Ph
HO
R2R1
R1 = C2H5; R2 = H
An Approach to New Acrolein β-Anion Equivalent
5
O
ZR3SiR3Si
O
Zbase
El+
Z
H
R3Si
O
El+
ZR3SiO
El
H
desilylationelimination
O El
H
Z = leaving group
O
ZR3Si
Acrolein !-Anion Equivalent
H
O
New Acrolein β-Anion Equivalents6
Preparation of γ-(p-Toluenesulfonyl)-α,β-epoxysilane
tBuMe2Si
O
S
N
tBuMe2Si
O
S S
N
tBuMe2Si
O
S
N
O
Me3Si
O
SO2pTol
tBuMe2Si
O
OTf
tBuMe2Si
O
SO2pTol
tBuMe2Si OH tBuMe2Si OH
OmCPBA
Na2HPO4, CH2Cl2
(100%)
MsCl
Et3N, CH2Cl2
tBuMe2Si OMs
O NaI
acetone tBuMe2Si I
O
p-TolSO2Na
DMF tBuMe2Si SO2p-Tol
O
(72% 2 steps)
(80%) mp 76 °C
7
PhCH2Br
NHMDS, THF-80 ° to -40 °C
tBuMe2SiO SO2p-Tol
CH2Ph
PhO
n-Bu4NF, THF
-70 °C, 15 min
(88%) (85%)
tBuMe2Si SO2p-Tol
O
H(E/Z = 2.0)
Reaction of γ-Methalated γ-Sulfonyl-α,β-epoxysilane with Electrophile Followed by Desilylation with Concomitant Elimination of the Sulfonyl Group (I)
1. BnBr (1.0 eq), NHMDS (1.0 eq), -80 ° to -60 °C, 40 min2. TBAF (1.1 eq), THF (0.1 M), -80 ° to -60 °C, 30 min
1. BnBr (1.0 eq), NHMDS (1.0 eq), -80 ° to -60 °C, 30 min2. EtOH (1.0eq), TBAF (1.1 eq), THF (0.08 M), -85 ° to -80 °C, 10 min
1. BnBr (1.05 eq), NHMDS (1.0 eq), -80 ° to -60 °C, 30 min2. EtOH (3.0eq), TBAF (1.1 eq), THF (0.08 M), -85 ° to -70 °C, 15 min
29
61
85
41
9
-
conditionsyield (%)
2 3
1. PhCH2Br, NHMDS2. n-Bu4NF
tBuMe2SiO SO2p-Tol
CH2Ph
PhO tBuMe2Si SO2p-Tol
O
2 31
+
Reaction of γ-Methalated γ-Sulfonyl-α,β-epoxysilane with Electrophile Followed by Desilylation with Concomitant Elimination of the Sulfonyl Group (II)
8
tBuMe2Si SO2p-Tol
O 1. El (1.05 eq), NHMDS (1.0 eq) -80 ° to -50 °C
H El
O
El
Br
I(CH2)7CH3
product
H (CH2)7CH3
O
yield (%)
8482
H
O85
H (CH2)4OTBS
O
68
CO2EtI
OHC(CH2)4CH3
H
O
74
H
O
(CH2)4CH3 77
CO2Et
OH
I(CH2)4OTBS
El product yield (%)
2. TBAF (1.0 eq), EtOH (3.0 eq) -80 ° to -70 °C
Br (CH2)4CH3
H
(CH2)4CH3
O
An Approach to New Acrolein β-Dianion Equivalent9
R3Si
O
SO2p-Tolbase
El1
desilylationelimination
O El2
H
Acrolein !-Dianion Equivalent
H
O
SO2p-TolR3SiO
El1
H
base
El2SO2p-TolR3SiO
H
El2El1
El1
H
tBuMe2Si SO2p-Tol
O 1. NHMDS (1.0 eq), R1X (1.1 eq), -80 ° to -40 °C
2. NHMDS (4.0 eq), R2X (1.3 eq), -80 ° to -55 °C
3. TBAF (1.0 eq), EtOH (3.0 eq), -80 ° to -70 °C H
O
THF
R2
R1
product yield (%)
I(CH2)7CH3
I(CH2)7CH3
R1X
H
O Et
(CH2)7CH3
H
O (CH2)7CH3
(CH2)7CH3
52
76
R2X
IEt
I(CH2)7CH3
Application of the Epoxysilane Rearragement to Wittig-Type Olefination Reaction
10
tBuMe2Si
O
IPPh3
R3Si
O
PPh3 I
conditions benzene, reflux ether, rt CH2Cl2, rt
tBuMe2Si I
O
80%
P(OMe)3 tBuMe2Si P(OMe)2
O O LDA, CH3(CH2)4CHO
tBuMe2SiO P(OMe)2
O
C5H11HO
38%THF-80 ° to 10 °C
R3Si
O
P(OR)2
O
R3Si
O
PPh2
O
R3SiO
R'
R
Horner-Wadsworth-Emmons Reaction
R3Si
O
PPh3Wittig ReactionX
tBuMe2Si
O
XtBuMe2SiO XtBuMe2Si
O
XBase
RCOR'
Wittig-Horner Reaction
Preparation of γ-Phosphinoyl-α,β-epoxysilane
11
Reactions of γ-Phosphinoyl-α,β-epoxysilane with Cyclohexanone
tBuMe2Si PPh2
O O1. base, -80 °C, 10 min
2. cyclohexanone tBuMe2SiO PPh2
OHO
2
tBuMe2SiO
tBuMe2SiO PPh2
OH
base
n-BuLi
n-BuLi
NaN(SiMe3)2
NaN(SiMe3)2
KN(SiMe3)2
additive
-
HMPA
-
HMPA
HMPA
3
-
13
20
15
-
2
31
3
-
-
-
1
29
26
28
31
53
yield (%)KHMDS, THF
-80 °C, 15 min
3
1
tBuMe2Si OH tBuMe2Si Br
NBS, Me2S
CH2Cl255% (4 steps)
1. LiPPh2, THF
2. H2O2
tBuMe2Si PPh2
O
tBuMe2Si PPh2
OOmCPBA
CH2Cl2
85%
78%
OEE3 steps
mp 108 °C
Reactions of γ-Phosphinoyl-α,β-epoxysilane with Ketones and Aldehydes
12
tBuMe2Si PPh2
O O1. n-BuLi, THF -80 °C, 10 min
2. ketone (aldehyde) -80 ° to -70 °C3. NaN(SiMe3)2 (3 eq) -80 °C to r.t.
tBuMe2SiO
R'
R
tBuMe2SiO
tBuMe2SiO
CH2CH3
CH3
tBuMe2SiO
CH(CH3)2
CH3
tBuMe2SiO
H
CH(CH3)2
tBuMe2SiO
H
yield (%) yield (%)
80
52
57
54
60
tBuMe2SiO
H
C5H1124
Preparation and Reactions of γ-Phosphonio-α,β-epoxysilane
13
tBuMe2Si
O
OH
Tf2O,pyridine
R3Si
O
PPh3
OTf
CH2Cl2
tBuMe2Si
O
OTf
PPh3
Et2O
86% (2 steps) mp 123 °C
tBuMe2Si PPh3
O 1. n-BuLi, THF -80 °C, 20 min
2. ketone (aldehyde) -80 ° to -30 °C
tBuMe2SiO
R'
R
tBuMe2SiO
tBuMe2SiO
H
tBuMe2SiO
H
Ph
tBuMe2SiO
H
yield (%) yield (%)
36
5174
63
tBuMe2SiO
H
C5H1159
OTf
Reactions of γ-Phosphonio-α,β-epoxysilane with Ketones and Aldehydes
14
tBuMe2Si PPh3
O 1. n-BuLi, THF/toluene (1 : 1) -80 °C, 20 min
2. ketone (aldehyde) -80 ° to -30 °C
tBuMe2SiO
R'
R
tBuMe2SiO
tBuMe2SiO
H
tBuMe2SiO
H
Ph
tBuMe2SiO
H
yield (%) yield (%)
54(-80 °C to rt)
77
76
69
tBuMe2SiO
H
C5H1173
OTf
Summary15
tBuMe2Si PPh3
O 1. n-BuLi
2. RCOR'
tBuMe2SiO
R'
R
tBuMe2Si PPh2
O O
1. n-BuLi
2. RCOR'
3. NaN(SiMe3)2 (3 eq)
OTf
El
tBuMe2Si SO2p-Tol
OH
O1. NHMDS, El
2. n-Bu4NF, EtOH
1. NHMDS, El1
2. NHMDS, El2
3. n-Bu4NF, EtOH
El2H
O El1
Reaction of γ-Methalated γ-Sulfonyl-α,β-epoxysilane with Electrophile Followed by Desilylation with Concomitant Elimination of the Sulfonyl Group (II)
16
tBuMe2Si SO2p-Tol
O1. El+ (1.05 eq), NHMDS (1.0 eq)2. TBAF (1.0 eq), EtOH (3.0 eq)
H El
O
El+
Br
(CH2)4CH3Br
I(CH2)7CH3
conditions
1. -80 ° to -50 °C, 40 min2. -80 ° to -70 °C, 20 min
product
H (CH2)7CH3
O
yield (%)
84
1. -80 ° to -50 °C, 30 min2. -80 ° to -70 °C, 15 min H
O
(CH2)4CH3 82
1. -80 ° to -60 °C, 30 min2. -80 ° to -70 °C, 15 min H
O
85
I 1. -80 to -40 °C, 45 min2. -80 ° to -70 °C, 15 min H
O
OTBS OTBS 68
Reaction of γ-Methalated γ-Sulfonyl-α,β-epoxysilane with Electrophile Followed by Desilylation with Concomitant Elimination of the Sulfonyl Group
17
tBuMe2Si SO2p-Tol
O
1. NHMDS (1.0 eq)2. El+ (1.05 eq), 3. TBAF (1.0 eq), EtOH (3.0 eq)
H El
O
El+
CO2EtI
conditions
1. -80 °C, 5 min2. -80 ° to -40 °C, 40 min3. -80 ° to -70 °C, 20 min
product
H
O
yield (%)
74
H
O
(CH2)4CH3 77
CO2Et
1. -80 °C, 5 min2. -80 ° to -60 °C, 20 min then CH3COOH (1.0 eq)3. -80 ° to -70 °C, 15 min
OH
OHC(CH2)4CH3
THF
OHC 1. -80 °C, 5 min2. -80 ° to -60 °C, 20 min then CH3COOH (1.0 eq)3. -80 ° to -70 °C, 15 min
H
O
OH
49
Methylation of Metalated O-Silyl Cyanohydrins of trans-β-Silyl-α,β-epoxyaldehydes
18
TBS
O
CN
OTBSH
TBS
O
CN
OTBSH
TBSO CN
OTBSCH3
H1B
SM
40
CH3I (1.2 eq)base (1.1 eq)
diastereomer
1A 1B
1A 1B 1A 1B 1A 1B
yield (%)
82 84
44 83
91 92
84 87
E/Z
2.522.0
23.031.0
40.047.0
0.9 9.7
base
LDA(in hexane/THF)
LiN(SiMe3)2 (1.0M in THF)
NaN(SiMe3)2 (1.0M in THF)
KN(SiMe3)2 (0.5M in toluene)
THF-80 °C !"5 min 2
R3Si
O
CN
OSiR3
H
R3Si CN
OSiR3O
R3Si
O
CN
OSiR3
Hbase
R3Si C
OSiR3O
N
base
1A 1B
1A
Solvent Effect on E/Z Selectivity
19
TBS
O
CN
OTBSH
TBSO CN
OTBSR
H1B
RX (1.2 eq)
Base (1.1 eq)
solvent/HMPA
-80 °C!"5 min 3
S#
1A 1B
1A1B
1A1B
1A1B
yield (%)
93 78
84 77
86 83
85 84
E/Z
1.5 6.0
1.928.0
1.024.0
28.052.0
solvent
hexane
ether
toluene
THF
1A
CN
OSiR3
CNR3SiO
OSiR3
CN
R3SiO OSiR3R
R3SiO Li
base
LDA
KHMDS
S#
1A 1A
1B1B
1A 1A
1B1B
HMPA
(–)(+)
(–)(+)
(–)(+)
(–)(+)
yield (%)
8261
8485
8492
8784
E/Z
2.528.0
22.0E
0.915.0
9.7E
SM (%)
-26
-8
--
--
Base: NHMDS, RX: BnBr solvent: THF, RX: CH3I
TBS
O
H
OTBSCN
CNR3SiO
OSiR3R
Alkylation of O-Silyl Cyanohydrins of β-Siloxyacrolein
20OTBS
H
CNTBSO
OTBSH
TBSO
CN THFH
CN
OTBSCH3
TBSO1.Base, 2.CH3I
-80 °C, 5 min(Z)-4
Base
LDA
LHMDS
NHMDS
KHMDS
LDA
LHMDS
NHMDS
KHMDS
yield (%)
76
46
81
75
41
0
30
76
E/Z
58.0
E
E
E
0.01
-
0.02
0.01
yield (%)
-
47
6
8
18
87
59
8
SM2
(E)-42
SM
E
E
E
E
Z
Z
Z
Z
or
CN
OSiR3
CNR3SiO
OSiR3
CN
R3SiO OSiR3
R
R3SiO Li
CNR3SiO
OSiR3
R
Base-Promoted Ring-Opening of Cyanohydrins of β-Silyl α,β-Epoxyaldehyde
21
TBS
O
CN
OTBSH
TBS
O
CN
OTBSH
TBSO CN
OTBSCH3
1B2
35
26
E/Z
6.6
25.0
1
40
67
A:B
1.00:0.70
1.00:0.76
HMPA
(–)
(+)
1A:1B = 1.00:1.04
CH3I (0.5 eq)LDA (0.5 eq)
2
THF-80 °C, 5 min
+
1
+
yield (%) yield (%)
H
O SiR3
HH
R3SiO CN
R'2N
M
1A
O SiR3
HH
NC OSiR3
R'2N
M
1B
syn-elimination
O SiR3
H
H
HNC OSiR3
NR2
O SiR3
H
H
HR3SiO CN
NR21B1A
anti-elimination
1A
TBS
O
H
OTBSCN
A-value: OTMS = 0.7 CN = 0.2
Substituent Effect of the Silyl Group on Rates of Ring Opening
22
1B 1B2
6B
ButPh2SiO CN
OTBSCH3
6B7
CH3I (0.7 eq) Base (0.7 eq)
THF -80 °C, 5 min
ButMe2SiO CN
OTBSCH3
O SiR3
H
H
HR3SiO CN
NR21B
!"
1B
24.4
18.1
19.4
6B
39.1
39.8
29.8
2
18.8
21.5
22.1
7
6.0
6.7
14.8
7 (TBDPS)/2 (TBS)
0.32
0.31
0.67
yield (%) yield (%)
base
LiNEt2
LDA
LTMP
ButMe2Si
O
H
OTBSCN
ButPh2Si
O
H
OTBSCN
ButMe2Si
O
H
OTBSCN
ButPh2Si
O
H
OTBSCN
LTMP =N
TBS = ButMe2Si
TBDPS = ButPh2Si