the Role of Silicon in Substitution of Furan

By: Andy Arifin Tjeng

Outline

Introduction Role of Silicon in Furan substitution Conclusion

Carbon-Silicon bond

Bond Length: 1.89 Bond strength: ~ 300 kJ/mol Partly polarized bond Carbon-Silicon bonds does not occurs naturally. No natural product containing silicon has been found.

-Effects

+ R'

SiR3

Stabilization of carbocation at -position. Possibility from donation of C-Si bond to empty p orbital. Maximum stabilization at 90 angle from cations Other possibiltiy: hyperconjugation

Si

+Si

-Effects

R' ..

SiR3

Stabilization of carbanion at -position. Possible reason: backbonding interaction, similar to Si-O bond (full p orbital interaction with empty d orbital from Si)

SIR3

Arylsilanes

Synthesis: Grignard reaction

MgX SiR3

SiR3Cl

Cycloaddition reaction
SiMe 3 + SiMe 3 CpCo(Co)2 SiMe 3 SiMe 3

Removal: Fluoride ion

ipso-substitution

Ipso-Substitution with Electrophiles Reason: stabilization from -effects

SiMe 3 E+ E SiMe 3 + E

Substitution of Furan

Attack of electrophiles are C-2 or C-5 site Substitution at C-3 results in regioisomers of C-2 and C-5 position.
O

Silyl group in substitution of Pyrroles

Br NBS N Si(iPr)3 N Si(iPr)3 Br Bu4N+ FN

ipso-substitution of Furan

First reported in 1948 by Benkeser and Currie

1) BuLi 2) SiMe3Cl O O 1) BuLi 2) CO2 SiMe 3 HOOC O Br2 SiMe 3

HOOC

Br

3,4-substituted Furan
CH2OSiR3 BuLi, HMPA O THF, rt O SiR3 2.2 eq. BuLi electrophiles R' CH2OSiR3 NaH, DMF O O SiR3 R' CH2OH Bu4N+ FO R' CH2OH CH2OH

3,4-substituted Furan
O OSiR 3 O 1) BuLi, HM PA THF, rt 2) 10% HCl O O OH SiR 3 1) 2.2 e q. BuLi 2) e le ctrophile s 3) 10% HCl O R' OMe 1) n-Bu4NF, THF 2) CH2N2 O R'

O OH

SiR3

2,4-Substituted Furan
CH2OSiEt3 1) BuLi, HM PA O R Si(t-Bu)Me 2 THF, -40o 2) e le ctrophiles O Si(t-Bu)Me 2 Ac2O-THF-H2O (8:8:1) R O CH2OSiEt3 CH2OH

CH2OSi(t-Bu)Me 2

Bu4N+ FCH 2N2 R O

CH2OH

Si(t-Bu)Me 2

Synthesis of 3,4-Furan
Ph N O SiMe 3 SiMe 3 SiMe 3

+
SiMe 3 O

MeOOC

COOMe

MeOOC

COOMe

3,4-substituted Furan
SiMe 3 SiMe 3 SiMe 3 I SiMe 3 He ck, Stille , Suzuki coupling R O I2, CF3COOAg O O 1) BCl3, -78oC 2) 5% HCl I R I2, AgBF4 O R'CCH, PdCl2, CuI, Et2NH O R R O B R O O B B O R R'X, R' O Pd(PPh ) 3 4 tolue ne -M e O 120oC, 14-18 h R

R'

2,3-substituted benzene
SiMe 3 SiMe 3
o se ale d tube , 160 SiMe 3 (CF3CO)2O

BuLi, THF RX O SiMe 3

SiMe 3 SiMe 3 I2 CF3COOAg

cat CF3COOH, CCl4, 24 h

R'

1) BCl3 SiMe 3 2) R'X, Pd(PPh3)4 tolue ne -M e OH 120oC, 14-18 h R

LiAlH4 THF O

SiMe 3 I

2,3,4-substituted Furan
SiMe 3 SiMe 3 I SiMe 3 BuM gCl Ni(PPH3)2Cl2 THF, 80oC, 3 h O Br I I2, AgBF4 THF, -78oC Bu Bu tBuLi, THF Bu

2,3,5-substituted furan
Me 3Si p-C6H4M gBr Me Si 3 Ni(dppe )Cl 2 Et2O, 24 h I PhCH2 1) BCl3 2) ArX, Pd(PPh3)4 tolue ne-M e OH C6H4Me-p Ar

PhCH2

120oC, 1-3 h PhCH 2

C6H4Me-p

Conclusion

The properties of Silyl group: bulkiness, ease of attachment and removal, migration tendency and ipso-substitution has been used to control substitution in furan ring.

References

Keay, B. A. Chem. Soc. Rev., 1999, 28, 209-215