Silyl Ethers - Thieme Chemistry

Scheme 17 Silylation with tert-Butyldimethylsilyl Chloride and Imidazole [47]
HO
O
NMe 2
34
OH
OH
TBDMSCl, imidazole
DMF, 70 oC 94%
TBDMSO
O
NMe 2
35
OTBDMS
OTBDMS
(4S,5E)-9-(tert-Butyldimethylsiloxy)-4,8-bis(tert-butyldimethylsiloxymethyl)-N,N,4-trimethylnon-5-enamide
(35): [47]
A mixture of the triol 34 (100 mg, 0.366 mmol), imidazole (177 mg, 2.6 mmol), and
TBDMSCl (200 mg, 1.3 mmol) in dry DMF (5 mL) was kept at 70 8C overnight. The mixture
was partitioned between Et 2O and H 2O, and the ethereal soln was washed thoroughly
with H 2O, dried (MgSO 4), and evaporated. Purification on silica gel (Et 2O) afforded 35 as a
colorless liquid; yield: 214 mg (94%).
4.4.17.3.1.1 Variation 1:
In the Presence of4-(Dimethylamino)pyridine
Silylation of more sterically hindered alcohols, such as 36, with tert-butyldimethylsilyl
chloride requires replacement of imidazole (Section 4.4.17.3.1) with a stronger base such
as 4-(dimethylamino)pyridine. [48] Under these conditions, 36 can be converted into its tertbutyldimethylsilyl
ether 37 in high yield (Scheme 18). [49]
Scheme 18 Silylation with tert-Butyldimethylsilyl Chloride in the Presence
of 4-(Dimethylamino)pyridine [49]
H
HO
36
CN
TBDMSCl, DMAP
DMF, 21
81%
oC, 3 d
H
TBDMSO
rac-(5R)-5-[(1R,2E)-1-(tert-Butyldimethylsiloxy)penta-2,4-dienyl]-2,6,6-trimethylcyclohex-1eneacetonitrile
(37): [49]
To a soln of alcohol 36 (213 mg, 0.87 mmol) in dry DMF (5 mL) was added sequentially
TBDMSCl (170 mg, 1.13 mmol) and DMAP (270 mg, 2.21 mmol). The resulting soln was
stirred at 21 8C for 3 d. H 2O was added, the mixture was extracted with Et 2O, and the combined
extracts were washed with brine, dried, and concentrated. The residual oil was
chromatographed (petroleum ether/Et 2O 19:1) to give 37; yield: 254 mg (81%).
4.4.17.3.1.2 Variation 2:
In Dichloromethane
FOR PERSONAL USE ONLY
384 Science of Synthesis 4.4 Silicon Compounds
Replacement of dimethylformamide as the solvent (Section 4.4.17.3.1.1) by dichloromethane
has the effect of moderating the reactivity of tert-butyldimethylsilyl chloride, so that
the reagent becomes more selective in silylation of alcohols. Thus, the primary alcohol of
38 was protected as its tert-butyldimethylsilyl ether 39 in the course of work on lankacyclins
by using dichloromethane as the solvent (Scheme 19). [50] An advantage of dichloromethane
over dimethylformamide is its easier removal from the product, but since imi-
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG
37
CN