Silyl Ethers - Thieme Chemistry

complete. The reaction was quenched at ±788C by the addition of a sat. NH 4Cl soln. The
aqueous layer was extracted with EtOAc, and the extract was concentrated under vacuum.
Purification of the residue by flash chromatography (silica gel, hexane/EtOAc 3:1)
gave 41 as a white solid; yield: 363 mg (90%).
4.4.17.3.2.1 Variation 1:
Selective Silylation ofPhenols
Silylation with tert-butyldimethylsilyl trifluoromethanesulfonate at low temperature can
be used to discriminate between phenols and aliphatic hydroxy functions, as in the conversion
of 42 into the aryl silyl ether 43 (Scheme 21). [53] This reaction illustrates the general
observation that phenols are converted into their tert-butyldimethylsilyl ethers more
rapidly than are aliphatic alcohols.
Scheme 21 Selective Silylation, with tert-Butyldimethylsilyl Trifluoromethanesulfonate, of
a Phenol in the Presence of an Aliphatic Alcohol [53]
MeO
OBn
OMe
O
42
4'
OH
FOR PERSONAL USE ONLY
386 Science of Synthesis 4.4 Silicon Compounds
OH
TBDMSOTf, 2,6-lut, CH 2Cl2, −78 o C, 5 min
90% (2 steps from the 4'-OMEM derivative)
MeO
OBn
OMe
O
43
OH
OTBDMS
(1R)-1-[(2R,3S)-9-Benzyloxy-4-(tert-butyldimethylsiloxy)-6,7-dimethoxy-2,3,8-trimethyl-2,3dihydronaphtho[1,2-b]furan-3-yl]-4-methylpent-3-en-1-ol
(43): [53]
The crude diol 42 (16 mg, prepared in situ from the 4¢-OMEM derivative) was dissolved in
CH 2Cl 2 (1 mL), to which was added 2,6-lutidine (26.1 mg, 0.24 mmol) and TBDMSOTf
(38.1 mg, 0.14 mmol) at ±788C. After the soln was stirred for 5 min, the reaction was
quenched by adding pH 7 phosphate buffer, and the products were extracted with EtOAc.
The combined organic extracts were washed with brine, dried (Na 2SO 4), and concentrated
in vacuo. The residue was purified by preparative TLC (hexane/EtOAc 7:3) to give aryl silyl
ether 43 as a pale yellow oil; yield: 13.0 mg (90% for 2 steps from the 4¢-OMEM derivative).
4.4.17.3.2.2 Variation 2:
Selective Silylation ofAlcohols
The effect of reaction temperature on selectivity in silylation with tert-butyldimethylsilyl
trifluoromethanesulfonate can be striking, as seen in the conversion of triol 44 into the
bis(tert-butyldimethylsilyl ether) 45 at ±208C (Scheme 22). [54] Although both secondary hydroxy
groups in this cis-fused decahydronaphthalene are equatorial, only the alcohol that
is remote from the quaternary center is silylated. In structures such as 44, where two hydroxy
substituents are in spatial proximity, the initial silylation of one hydroxy group will
often retard reaction of the second hydroxy with this silylating agent, due to steric reasons.
This will, of course, augment selectivity arising from a temperature effect.
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG