Silyl Ethers - Thieme Chemistry

Scheme 30 Selective Cleavage of a tert-Butyldimethylsilyl Ether with Hydrochloric Acid [65]
TIPSO
O
OTMS
TBDPSO
OTBDMS
60
O
O
Pr i
TIPSO
O
10% aq HCl
THF, rt, 3 h
87%
OH
TBDPSO
(3E,3aS,4S,6S,7S,7aR)-3-{(2E,4R,6E)-8-[(2R,4S,8R,9S)-4-(tert-Butyldiphenylsiloxy)-8-isopropyl-9-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-4,6-dimethylocta-2,6-dienylidene}-4-(hydroxymethyl)-6-methyl-7-(triisopropylsiloxy)hexahydrobenzofuran-3a(4H)-ol
(61): [65]
To a soln of tetrakis(silyl ether) 60 (0.41 g, 0.36 mmol) in THF (40 mL) was added 10% aq
HCl (5.5 mL). The mixture was stirred at rt for 3 h and cooled to 0 8C. Solid NaHCO 3 was
added carefully in small portions until all the bubbling subsided. The aqueous layer was
extracted with Et 2O (4 ” 20 mL), and the combined organic extracts were dried (MgSO 4),
filtered, and concentrated in vacuo. Purification of the residue by column chromatography
(silica gel, 5±10% EtOAc/hexanes) provided diol 61 as a white foam; yield: 0.30 g (87%).
4.4.17.3.6.3 Variation 3:
With Organic Acids
Organic acids used for cleavage of tert-butyldimethylsilyl ethers include formic, [66] acetic,
[67] trifluoroacetic, [68] and certain sulfonic acids. [69] Formic acid is the least selective of
these reagents, showing little discrimination in the cleavage of tert-butyldimethylsilyl
ethers in different steric or electronic environments. An example of a deprotection with
this reagent is the reaction of the bis(tert-butyldimethylsilyl ether) 62 to give lankacidin C
(63, Scheme 31). [66]
Scheme 31 Cleavage of tert-Butyldimethylsilyl Ethers with Formic Acid [66]
O
O O
TBDMSO OTBDMS
62
O
HN
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 393
O
HCO2H, THF
H2O, rt, 3 h
86%
OH
61
O
O
HN
O O
O
Pr i
HO OH
The use of trifluoroacetic acid for cleavage of tert-butyldimethylsilyl ethers is confined to
compounds that are stable to a moderately strong acid, but the reagent can offer a valuable
means for selective cleavage of these ethers. For example, the bis(tert-butyldimethyl-
63
O
O
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG