Silyl Ethers - Thieme Chemistry

4.4.17.2.2 Method 2:
Silylation ofAlcohols with Triethylsilyl Trifluoromethanesulfonate
Triethylsilyl trifluoromethanesulfonate (TESOTf) [40] is now available commercially. It is often
employed for the triethylsilylation of less reactive alcohols and is invariably used in
the presence of pyridine or a substituted pyridine. The conversion of alcohol 24 into its
triethylsilyl ether 25, an intermediate in a route to various macrolides, illustrates an
application of this reagent (Scheme 12). [41] The presence of both triethylsilyl and triisopropylsilyl
ethers in 25 was a design element that permitted selective cleavage of the triethylsilyl
ether at a later step in the synthesis.
Scheme 12 Silylation with Triethylsilyl Trifluoromethanesulfonate [41]
O
O
N
O
Bn
24
OH OTIPS
TESOTf, 2,6-lut
CH2Cl2, rt
99%
O
O
N
O
Bn
25
OTES OTIPS
(4R)-4-Benzyl-3-[(2R,3S,4R,5R)-2,4-dimethyl-1-oxo-3-(triethylsiloxy)-5-(triisopropylsiloxy)hexyl]oxazolidin-2-one
(25): [41]
To a soln of alcohol 24 (1.835 g, 3.74 mmol) in CH 2Cl 2 (75 mL) at rt was added 2,6-lutidine
(0.653 mL, 5.61 mmol), followed by TESOTf (0.930 mL, 4.11 mmol). The resultant colorless
soln was stirred for 40 min before the addition of sat. aq NaHCO 3 (50 mL). The layers were
separated, and the aqueous layer was extracted with CH 2Cl 2 (2 ” 30 mL). The combined organic
phases were washed with 1 M NaHSO 4 (20 mL), H 2O (20 mL), and brine (20 mL), dried
(Na 2SO 4), filtered, and concentrated in vacuo. The product was purified by flash chromatography
(5 ” 15 cm silica gel column, EtOAc/hexanes 1:9) to give 25 as a clear colorless
oil; yield: 2.28 g (99%).
Cleavage
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380 Science of Synthesis 4.4 Silicon Compounds
4.4.17.2.3 Method 3:
Cleavage ofTriethylsilyl Ethers under Acidic Conditions
Although triethylsilyl ethers are more stable toward acidic reagents than their trimethylsilyl
counterparts, [42] they can be cleaved under acidic conditions to give the parent alcohol
in good yield. Hydrogen fluoride±pyridine complex is a commonly used reagent for
accomplishing this cleavage, and is often selective, as the example in Scheme 13 illustrates.
Thus, the triethylsilyl ether of 26 was removed in the presence of hydrogen fluoride±pyridine
complex without affecting either the triisopropylsilyl ether or the benzylidene
acetal in this structure. [41] The resultant alcohol 27 was obtained in nearly quantitative
yield.
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG