Silyl Ethers - Thieme Chemistry

Trimethylsilyl cyanide (TMSCN) is a reagent used for silylation where the presence of a
base must be avoided. [26] Since the byproduct, hydrogen cyanide, is volatile and not sufficiently
acidic to be deleterious, silylation can be carried out with the neat reagent or in a
neutral solution. The reagent rapidly silylates alcohols, phenols and carboxylic acids, but
reacts only slowly with amines and thiols. Amides are not silylated with this reagent. An
example illustrating the application of this reagent is the conversion of the sensitive
calicheamicinone precursor 5 into its trimethylsilyl ether 7 via the tris(silyl ether) 6
(Scheme 3). [27] It is noteworthy that only the primary trimethylsilyl ether of intermediate
6 is cleaved during workup in the presence of aqueous acetic acid.
Scheme 3 Silylation with Trimethylsilyl Cyanide [27]
TESO
NHCO2Me
OH
FOR PERSONAL USE ONLY
374 Science of Synthesis 4.4 Silicon Compounds
OBoc OBoc
Me 3SiCN
TESO
HO TMSO
5 6
AcOH, H2O, THF
99%
NHCO2Me
OTMS
TESO
HO
OBoc
7
NHCO2Me
OTMS
Methyl 11-(tert-Butoxycarbonyloxy)-13-(2-hydroxyethylidene)-1-(triethylsiloxy)-8á-
(trimethylsiloxy)bicyclo[7.3.1]trideca-4,9,11-triene-2,6-diyn-10-ylcarbamate (7): [27]
A soln of 5 (465 mg, 0.85 mmol) in TMSCN (1 mL) was stirred for 30 min and the volatiles
were evaporated in vacuo. The residue was dissolved in a mixture of THF (50 mL), H 2O
(10 mL), and glacial AcOH (1 mL). The mixture was stirred for 30 min (with close monitoring
by TLC, Et 2O/petroleum ether 1:1), diluted with Et 2O (150 mL), washed with sat. aq
NaHCO 3 (2 ” 50 mL), dried (MgSO 4), filtered, and evaporated in vacuo to give 7 as a pale
yellow, solid foam; yield: 518 mg (99%).
4.4.17.1.4 Method 4:
Silylation ofAlcohols with N,O-Bis(trimethylsilyl)acetamide
N,O-Bis(trimethylsilyl)acetamide (BSA) is a relatively unselective reagent that can convert
hindered alcohols into their trimethylsilyl ethers when used in dimethylformamide at elevated
temperature (80±1008C). [28] The byproduct acetamide must be removed, often requiring
chromatography for purification of the silyl ether. The related reagent N,O-bis(trimethylsilyl)trifluoroacetamide,
[29] although used less frequently, has the advantage that
the byproduct, trifluoroacetamide, is removed more easily since it is quite volatile. An application
of N,O-bis(trimethylsilyl)acetamide is seen in the conversion of the alcohol 8
into its trimethylsilyl ether 9 (Scheme 4), an intermediate in a synthetic route to azinomycin.
[30]
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG