Properties of Silicon
Baran Lab
Hafensteiner
Siliconium Ion
Si vs. C
- Si is less electronegative than C
- Not believed to exist in any reaction in solution
- More facile nucleophilic addition at Si center
J. Y. Corey, J. Am. Chem. Soc. 1975, 97, 3237
- Pentacoordinate Si compounds have been observed
Average BDE (kcal/mol)
C–C
83
C–Si
76
C–O
86
Si–Si
53
Si–O
108
MeSiF4 NEt4
C–F
116
C–H
83
Si–F
135
Si–H
76
Ph3SiF2 NR4
- Lack of cation justified by high rate of bimolecular reactivity at
Si
Mechanism of TMS Deprotection
OTMS
O
Average Bond Lengths (Å)
C–C
C–Si
C–O
Si–O
1.54
1.87
1.43
1.66
Silicon forms weak p-Bonds
Workup
O
Si
F NBu4
O
Si
F
p - C–C = 65 kcal/mol
p - C–Si = 36 kcal/mol
Pentavalent Silicon
Properties of Silicon
Baran Lab
Nucleophilic addition to Si
F
RO–SiMe3
b-Silicon effect and Solvolysis
RO
F–SiMe3
SiMe3
H
Me3C
OSiMe3
O
Li
H
Me3C
OCOCF3
H
B
H
b-Silicon Effect
H
kA / kB = 2.4 x 1012
Duhamel et al. J. Org. Chem. 1996, 61, 2232
- Silicon stabalizes b-carbocations
- Stabalization is a result of hyperconjugation
H
H
Me3C
H
SiMe3
vs.
H
Me3C
OCOCF3
H
Me
OCOCF3
kA / kB = 4 x 104
CR3
Evidence for Stepwise mechanism
vs.
Me3Si
B
*A is more stable than B by 38 kcal/mol *
Jorgensen, JACS, 1986,107, 1496
vs.
A
Me-SiMe3
A
H
Me
OCOCF3
H
MeLi
SiR3
Hafensteiner
SiMe2Ph
Me3Si
Me3Si
SiMe2Ph
SiMe2Ph
SiMe2Ph
Me3Si
Product ratios are equal from either starting material suggesting
common intermediate cation
Properties of Silicon
Baran Lab
Evidence for Rapid Nucleophilic Attack
SiMe3
Extraordinary Metallation
Me
SiMe3
SnCl4
Me3Si Cl
Cl
MeO OMe
OMe
Si
Me
Li
t-BuLi
Me2Si Cl
OMe
Me2Si
Cl
vs.
SiMe3
Gornowicz et al., J. Am. Chem. Soc. 1968, 90, 4478
SnCl4
Cl
MeO OMe
Hafensteiner
OMe
Cation-Anion Harmony
- Stabalization of a-anion and b-cation exemplified in
regioselectivity of the hydroboration of alkynlsilanes
OMe
Fleming et al., JCS Chem. Com. 1976, 182
Organosilanes Stabilize C–M Bonds
- Metallation occurs a to silicon
- Hyperconjugation gives stability
R
SiMe3
R2BH
R
d+
SiMe3
d-
BR
H d+ 2
d-
Zweifel et al., J. Am. Chem. Soc. 1977, 99, 3184
Me
Me
Me
M
Si
R
R
SiR3
R
BR2
H
Allylic and Vinylsilanes
Baran Lab
Hafensteiner
Silicon Migration
Vinylsilane Reactivity
- Conjugate addition can be followed by Si migration
- Migration aptitude enhanced when Si has bulky R groups
- React with electrophiles
- Regioselectivity governed by creation of b-carbocation
- Elimination of SiR3 occurs with retention of initial double bond
geometry due to principle of least motion
- Limited rotation also prevents eclipsing interactions between
silyl group and olefin substituents
O
Me
TiCl4
Me
(i-Pr)3Si
CH2Cl2
O
Vinylsilane Examples
(i-Pr)3Si
Et
OTiCl4
Et
OTiCl4
Me
SiMe3
ClCH(OMe)2
TiCl4
Et
Et
OMe
Me
Si(i-Pr)3
Si(i-Pr)3
A. I. Meyers, J. Org. Chem. 1998, 63, 5517
N
H
NH SiMe3
(CH2O)n
TsOH
N
N
H
Me
MeO2C
CO2Me
R(i-Pr)2Si
MeO2C
ZrCl4 MeO C
2
CH2Cl2
Ar
OMe
R = i-Pr, Ph
diasteromeric ratio 96:4, ~ 70% yeild
Ar
SiR3
Grieco et al. J. Chem. Soc. Chem. Comm., 1987, 185
Reactions with Silicon
Sakurai Reaction
- Lewis acid catalzed addition of allysilanes to aldehydes and
acetals
OMe
Me3Si
n-C4H9
MeO
OMe
Me3Si
O
OMe
R
TMS
H
TMS
H
OTMS
BF3•Et2O cat.
R
H
n-C4H9
83%
Intramolecular Sakurai Reaction
O
H
Me3Si
Me
TMS
R
R
O
LA
RCHO
R
R
O
Me3Si
O
Markó et al. Tett. Lett.,1992, 33, 1799
R
R
Me
Me
~65
:
35
O
Me3Si
75 %
OTiCl4
Me
Me
O
Me3Si
Me3Si
OTMS
17 %
Fleming, Org. Reactions 1989, 37, 127-133
Me
H
OH
Me
TMS
H
OH
CH2Cl2
Me
Me
H
TiCl4
O
SiMe3
Me
EtAlCl2
OH
O
R
Me
Conjugate Addition
H
R
>95:5
syn:anti
R
Hyashi, Tett. Lett. 1983, 2865.
OTMS
H
H
OTMS
OH
CH2Cl2
ene reaction
H
TiCl4
n-C4H9
80%
TiCl4
n-C4H9
MeO
O
R
OMe
TiCl4
Examples of Addition to Carbonyls
O
CH2Cl2
78%
Majetich, Tetrahedron 1987, 43, 5621
O
Brook Rearrangement
Baran Lab
Pioneering Work By A. G. Brook
- Rearrangement of organosilyl alcohols under base catalysis
- Retention at silicon and inversion at carbon
R3Si
OH
Ph
Ph
Ph
SiR3
Ph
O
H
Et2NH
DMSO
- Brook rearrangement can be used to access homoallylic
enolate anions
O
R
Li
SiR3
Et2NH
Ph
Ph
PhS
H
N
LiO
PhS
Examples of Brook Rearrangement
R
SiR3
Li
R1
R3Si
R
O
SiR3
O
OLi
OSiR3
[1,2]
PhS
E
O
R
R
OSiR3
OLi
SiR3
R
R
Takeda, J. Am. Chem. Soc. 1993, 115, 9351
Takeda, Synlett. 1994, 178
Takeda, Synlett. 1997, 255
OLi
Moser, Tet. 2001, 57, 2065-2084
PhS
R
O
R3Si
R
R
H
Brook, Accts. Chem. Res. 1974, 7, 77-84
El
OLi
O
H N
O
R
OSiR3
SiR3
R3Si
O
Ph
Ph H
O
(CH2)4 I
Reich, J. Am. Chem. Soc. 1980, 102, 1423
O
R3Si
Hafensteiner
PhS
PhS
R
Moser, Tett. 2001, 57, 2065-2084
OLi
R
Peterson Olefination
Baran Lab
Pioneering Work By Peterson
- Investigation aimed at finding a silicon analog to phosphorous
ylides
- Same cyclic four-membered transition state can be envisioned
O
R3Si
M
R3Si
OM
R3Si
O
H
O
H
H
R
O
R1
Li
TMS O H
H
O
OMe
H
H
2. SiO2, benzene
R1
OM
R3Si
TMS
1.
R
R1
R
H OMe
OMe
Hafensteiner
TMS O H
H O
R
R1
H
O
H
1. H2·Rh-Al2O3
H
2. BF3·Et2O
H
O
OMe
H
H
Peterson, J. Org. Chem. 1968, 33, 780-784
LA
- Mg alkoxides are stable and do not breakdown to give olefin
product
- Li, Na, and K alkoxides are reactive and breakdown to give
olefin product
- b-silyl-alcohols can be converted to olefins with dilute acid
OH
R3Si
R
R
10% H2SO4
RT
R
R
R3Si
OH
OH
O
TMS
BF3•Et2O,
MeOH
OH
OMe
OH
O
TMS
MeOH
OH OH
SiMe3
OMe
Whitmore et al., J. Am. Chem. Soc. 1947, 69, 1551
Ager, Org. Reactions 1990, 38, 1.
Tamao Oxidation
Tamao Oxidation
Representative Silanes
- Conversion of organosilanes to corresponding alcohols
- Pioneered by Tamao in 1984 (Tett. Lett. 1984, 25, 4249)
CH2MgBr
Me2Si
O
O
O
RMe2Si
N
RMe2Si
O
RMe2Si
S
RMe2Si
SPh
Si
Me2
CuI cat.
KHF2
TFA
O
RMe2Si
RMe2Si
MeO
SPh
O
30% H2O2
OH
NaHCO3
F
Si
Me2
RSiMe2Tol-p
RSiPh3
Yoshida et al. J. Org. Chem. 1999, 64, 8709
68% overall
- Other substrates used and in all cases no Bayer-Villager
seen
O
O
O
Synthetic Example
1. BF3·AcOH
Me2Si
O
Ph
N
Ph
O
2. 35% H2O2
NaHCO3
95%
Weinreb et al. J. Org. Chem. 2002, 67, 4339
HO
N
Ph
O
Silicon in Synthesis
Baran Lab
Brook Rearrangement
Hafensteiner
Cyanthin Tricyclic Core
PhMe2SiO
O
SiMe2Ph
Me
MeO
OLi
0 °C to rt
47%
dysidiolide
i-Pr
O
Me
OMe
i-Pr
HO
HO
O
O
OTBS
O O
TMS OH
13 Steps
PhMe2Si
O
Me
i-Pr
O
PhMe2SiO
OLi
O
Me
OMe
i-Pr
OMe
H
TBDPSO
OH
O
1. BF3, –78°C
2. PPTS, EtOH
OLi
TMS Me
Me
6 steps
Product
i-Pr
–80 °C to 0 °C
60%
H
TBDPSO
Corey, Roberts, J. Am. Chem. Soc. 1997, 119, 12425 - 12431
O
TBS
Takeda et al. Org Lett. 2000, 2, 1907
OTBS
SiMe3
i-Pr
Silicon in Synthesis
Baran Lab
Brook Rearrangement
H
OH
Hafensteiner
O
(+)-onocerin
O
TMS
TfO
TMSCH2ZnBr
OTf
HO
Pd(PPh3)4
O
H
TMS
O
Li
O
Li
TBS
OTBS
-78 °C
O
H
OH
1. MeAlCl2
15 min
2. TBAF
O
0.5 equiv I2
O
CsF
TfO
OTf
O
O
TBSO
PhNTf2
HO
H
Mi, Schreiber, Corey, J. Am. Chem. Soc. 2002, 124, 11290-11291
OTBS
O
- Properties of silicon exploited
- b-carbocation stabalization
- a-anion stability
Silicon in Synthesis
Baran Lab
(+)-Tetronomycin
- Stabalization of b-cation
–MeO
OH
H
Hafensteiner
MeO
H
O
HOH
H
OH
OTBDPS
OH
+MeO
OTBDPS
OMe
OH
H
O
R
O
O
H
O
H
1
OH R
TMS
R
H
O
H
SiMe3
OMe
- Key coupling step in convergent synthesis uses allysilane
coupling reaction
H
H
O
H
PivO
MeO
TMS
H
PivO
H
H
H
OH
OTBDPS
OH
H
OH
H
OTBDPS
BF3•Et2O, 92%
O
O
PivO
OH
H
O
H
HOH
OH
OTBDPS
O H R1
H
O
O
O
Yoshi et al. J. Org. Chem. 1992, 57, 2888
OMe
Silicon in Synthesis
Baran Lab
O
H
(±)-Hirsutene
H
D
CO2Et
O
H
H
1. H2 / Pt / C
2.
CO2Et
HH
1. LiAlH4
2. PDC
72%, 2 steps
TMS
TMS
H
Me3SI, NaH
H
H
DMSO
60%
H
H
(±)-Sarain A Core Scaffold
O
O
N
OH
N
H
PdCl2, CuCl
O
O2
76%
H
Sarkar et al. Tett. Lett., 1990, 31, 3461
1. TiCl4
2. PCC
53%
H
H
H
97%
O
O
H
H
5% KOH
40%
TMS
TMS
Hafensteiner
HO
O
H
H
O
Sarain A
Silicon in Synthesis
(±)-Sarain A Core Scaffold
O
(+)-Pumiliotoxin A
O
O
BnN
OTHP
NBn O
65%
O
BnN
H Bn
N
H
H
Bn
N
1. Swern [O]
2.
MgBr
C4H9
BnN
O
BnN
3. Ac2O, TEA, DMAP
4. (TMS)2CNLi2Cu
27%, 4 steps
H C H
4 9
TMS
Li
OH
NCO2Bn
Li
H
NBn
N
TMS
N
H
38%
Al(i-Bu)2Me
KOH, MeOH
H2O
80%
C4H9
(CH2O)n
TMS
NH
HO
TMS
Weinreb et al., J. Org. Chem., 1991, 56, 3210
O TMS
C4H9
CSA
HO
H
Al(i-Bu)2Me
O
H C H
4 9
O
TsN
Dibal-H;
MeLi
H
OH
H Bn
N
TsN
H
C4H9
H Bn
N
H
H
TMS
3. ClCO2Me
4. MeMgBr; CuI
35%, 4 steps
1. o-DCB, 320 °C
2. TsOH, MeOH
70%, 2 steps
TMS
1. Na, NH3, t-BuOH
2. LHMDS, TsCl, DMAP
3. Dibal-H
62%, 3 steps
H
1. (–)-pinene, 9-BBN
2. MeLi; TMSCl; HCl
O
OTHP H
Overman et al., J. Org. Chem., 1985, 50, 3670
C4H9
Silicon in Synthesis
Baran Lab
Hafensteiner
Prostoglandins
- Fleming contributed greatly to the field of organosilicon
chemistry
TMS
TMS
O
Cl
70%
Cl
Cl
MeOCH2Cl
SnCl4
78%
O
MeO
1. O3
O
2. Me2S
47%, 2 steps
MeO2C
CO2Me
Fleming, J. Chem. Soc. Chem. Comm., 1977, 79 - 80
Fleming, J. Chem. Soc. Chem. Comm., 1977, 81
2. Zn–AcOH–H2O
62%, 2 steps MeO
Cl
Cl
(±)-Linaridial
TMS
H
TiCl4
Loganin
TMS
TMS
O
OAc
O
1. H2O2–AcOH
O
OAc
O
0–5°C
Cl
OH
ClCH2SMe
77%
O
O
SMe
1. Raney Ni
2. CH2Br2,
Zn, TiCl4
OAc
Cl
Cl
ClSO2NCO
H
1. NaNO2, Ac2O
OAc
MeO2C
2. NaOAc
3. CH2N2
61%, 4 steps
OAc
ClO2SN
OH
OTMS
1. KNH(CH2)3NH2
2. Hydroboration/ [O]
H
Silicon in Synthesis
Baran Lab
(±)-Linaridial
CN OMe
OH
O
O
1. Swern [O]
H
2. Wittig
2. NaH
CN OMe
(OEt)2P
O
TMS
1. O3; Zn / HCl
OMe
H
Hafensteiner
TMS
Ph3P
OMe
1. Dibal-H
2. 1M HCl, THF
EtAlCl2
53%
50%
O
O
O
CHO
CHO
H
2
:
1
Tokoroyama et al. Tett. Lett., 1987, 28, 6645
(±)-a-Acoradiene
O
Li
O
O
P(OMe)2
61%
O
Yamamoto et al. J. Org. Chem., 1990, 55, 3971
:
2
Hydrosilation
Baran Lab
Hafensteiner
Hydrosilation
Reduction with Silanes
- Metal and radical catalyzed addition to alkenes and alkynes
- Metal catalysis is done at room temperature and best yields
obtained with trichloro and methyldichlorosilanes
- Addition of methyl grignard converts chlorosilanes to TMS
H
Cl3SiH
SiCl3
R
R
H2PtCl6
H
Cl3SiH
Cl3Si
R
R
H2PtCl6
- Catalysis needed for convenient rates
- Catalysts include TBAF, protic and Lewis acids, Wilkinson's cat,
silatrane
Chalk; Harrod; J. Am. Chem. Soc. 1965, 87, 16
-Cr(CO)6 with light gives 1,4 reduction of dienes
Germanes and Dehalogenation
- Organohalides can also be reduced with various
organogermanes
- Can be used catalytically with PPh3 for reduction of C–X bond
- Reactivity of halide I > Br > Cl > F
- Solid support methods can be used
- Similar reactivity to silanes
- Furanylgermane reduces C–X bond under mild conditions
O
GeH
3
P
(CH2)nEt2GeH
O
HO
H Si N
OO
H
Attar-Bashi et al. Organometallic Chem. 1976, 117, C87
Silanes and Dehalogenation
- Organohalides can be reduced with various organosilanes
- Radical mechanism of hydrodehalogenation
- Reactivity of halide I > Br > Cl > F
- Reactions are fast and clean often giving quantitative yields
-Common Silanes
S(i-Pr)
H
Si
(i-Pr)S
S(i-Pr)
SMe
H
Si
MeS
SMe
Et
Si
Et
H
Et
- Common Radical Intiators
AIBN
-"Common" Germanes
GeCl2•PPh3
O
Dibenzoylperoxide
- Phenylsilane is also used
- Reactions with phenylsilane are refluxed neat with a radical
initiator