Silyl Ethers - Thieme Chemistry

dazole has diminished solubility in dichloromethane alternative bases, usually 4-(dimethylamino)pyridine
or triethylamine, or sometimes both as in this case, are necessary to
achieve a sufficiently reactive silylating agent.
Scheme 19 Silylation with tert-Butyldimethylsilyl Chloride in Dichloromethane [50]
OH
CO 2Me
OH
38
TBDMSCl, Et3N
DMAP, CH2Cl2 73%
TBDMSO
39
CO 2Me
Methyl (3S)-4-(tert-Butyldimethylsiloxy)-3-hydroxybutanoate (39): [50]
Et 3N (16 g, 0.158 mol), DMAP (0.6 g, 4.9 mmol) and TBDMSCl (20 g, 0.133 mol) were added
to a soln of dihydroxy ester 38 (16.2 g, 0.121 mol) in CH 2Cl 2 (150 mL). The mixture was
stirred overnight then poured into H 2O. The two phases were separated and the aqueous
layer was extracted with CH 2Cl 2. The combined organic extracts were dried (MgSO 4) and
concentrated under reduced pressure. Chromatography of the residue gave 39 as an oil;
yield: 22 g (73%).
4.4.17.3.2 Method 2:
Silylation ofAlcohols with tert-Butyldimethylsilyl
Trifluoromethanesulfonate
The more powerful silylating agent tert-butyldimethylsilyl trifluoromethanesulfonate
(tert-butyldimethylsilyl triflate, TBDMSOTf) has become widely used for the preparation
of tert-butyldimethylsilyl ethers in spite of the fact that it is more susceptible to degradation
by moisture than tert-butyldimethylsilyl chloride and has a shorter storage lifetime.
[51] One reason for the popularity of this reagent is that whereas silylation of alcohols
can take many hours with tert-butyldimethylsilyl chloride, even with an excess of that reagent,
it occurs in minutes with tert-butyldimethylsilyl trifluoromethanesulfonate. As a
result, silylation with tert-butyldimethylsilyl trifluoromethanesulfonate can be carried
out at low temperature, a feature that is used to advantage in selective silylation of two
or more hydroxy groups in different steric environments. Thus, exposure of the steroidal
diol 40 to tert-butyldimethylsilyl trifluoromethanesulfonate in the presence of pyridine
at ±78 8C results in virtually instantaneous silylation of the 3-hydroxy substituent to give
41 whilst leaving the D-ring hydroxy untouched (Scheme 20). [52] As in this example, silylation
with tert-butyldimethylsilyl trifluoromethanesulfonate is almost always carried out
in dichloromethane as the solvent.
Scheme 20 Silylation with tert-Butyldimethylsilyl Trifluoromethanesulfonate [52]
HO
H
40
H
H H
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 385
Ac
OH
TBDMSOTf
py, CH2Cl2, −78 oC 90%
OH
TBDMSO
H
41
H
H H
3â-(tert-Butyldimethylsiloxy)-15â-hydroxy-5á-pregn-16-en-20-one (41): [52]
To a soln of diol 40 (300 mg, 0.9 mmol) in pyridine (5 mL) and CH 2Cl 2 (5 mL) cooled to
±78 8C was added dropwise a soln of TBDMSOTf (0.23 mL, 0.9 mmol) in CH 2Cl 2 (2 mL). Additional
TBDMSOTf in CH 2Cl 2 soln was added (0.1 equiv at a time) until the reaction was
Ac
OH
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG