Silyl Ethers - Thieme Chemistry

Scheme 41 Silylation of a Secondary Alcohol with tert-Butyldiphenylsilyl Chloride [87]
OH
83
CO 2Et
TBDPSCl, imidazole
DMF, 80 oC, 7 h
92%
CO 2Et
OTBDPS
84
Ethyl (2S)-2-(tert-Butyldiphenylsiloxy)-3-methylbutanoate (84): [87]
To a soln of ethyl (2S)-2-hydroxy-3-methylbutanoate (83; 2.22 g, 15.2 mmol) in DMF
(20 mL) were added imidazole (1.24 g, 18.2 mmol) and TBDPSCl (5.00 g, 18.2 mmol) and
the mixture was stirred at 808C. After being stirred for 7 h, the mixture was diluted with
H 2O (60 mL) and extracted with CH 2Cl 2 (3 ” 60 mL). The combined extracts were washed
with brine, dried (MgSO 4), and concentrated in vacuo. Column chromatography (silica
gel, hexane) gave silyl ether 84 as a colorless oil; yield: 5.40 g (92%).
4.4.17.5.1.1 Variation 1:
In the Presence of4-(Dimethylamino)pyridine
Silylation with tert-butyldiphenylsilyl chloride can be carried out at room temperature if
4-(dimethylamino)pyridine is included in the reaction mixture, [88] as seen in the quantitative
conversion of the hydroxyspiroketal 85 into its silyl ether 86 (Scheme 42). [65]
Scheme 42 Silylation with tert-Butyldiphenylsilyl Chloride in the Presence of
4-(Dimethylamino)pyridine [65]
HO
O
85
O Pr i
TBDPSCl, DMAP
imidazole, DMF, 25 oC, 60 h
100%
TBDPSO
O
86
O Pr i
(2R,3S,8S,10S)-10-(tert-Butyldiphenylsiloxy)-2-isopropyl-3-methyl-8-vinyl-1,7dioxaspiro[5.5]undecane
(86): [65]
To a soln of alcohol 85 (4.470 g, 17.6 mmol), imidazole (2.64 g, 38.7 mmol) and DMAP
(220 mg, 1.8 mmol) in dry DMF (300 mL) at 25 8C was added TBDPSCl (4.83 g, 17.6 mmol),
and the mixture was stirred for 60 h. To this soln was added pentane (500 mL) and H 2O
(300 mL). The aqueous phase was extracted with pentane (2 ” 100 mL), and the organic extracts
were combined and dried (Na 2SO 4). The extracts were concentrated and the residue
was purified by flash chromatography to give silyl ether 86 as a clear viscous oil; yield:
8.67 g (100%).
4.4.17.5.1.2 Variation 2:
Using Butyllithium
FOR PERSONAL USE ONLY
402 Science of Synthesis 4.4 Silicon Compounds
The reaction of butane-1,4-diol (87) with tert-butyldiphenylsilyl chloride at ±788C using
butyllithium as a base gives the monosilylation product 88 in high yield (Scheme 43). [89]
This useful method of desymmetrizing a diol is undoubtedly assisted by the large steric
bulk of the tert-butyldiphenylsilyl group.
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG