Silyl Ethers - Thieme Chemistry

(3R,4S,5R,6S,8S,9Z,11S,12S,13S,14Z,17S,18R,19R,20S,21S,22E)-6-(tert-Butyldimethylsiloxy)-20-hydroxy-4,18-bis(4-methoxybenzyloxy)-8,12-bis(methoxymethoxy)-
3,5,11,13,15,17,19,21-octamethylpentacosa-9,14,22,24-tetraen-2-one (29): [43]
To a cold (0 8C) soln of triethylsilyl ether 28 (40 mg, 0.035 mmol) in MeOH (5 mL) was
added TsOH·H 2O (ca. 2 mg, 0.010 mmol). The resultant mixture was stirred for 1 h at 0 8C.
Et 3N (2 mL) was added, and the mixture was concentrated under reduced pressure. The
residue was purified by flash chromatography (hexanes/EtOAc 4:1 to 2:1) to provide alcohol
29 as a clear oil; yield: 26 mg (72%).
4.4.17.2.3.2 Variation 2:
With Trifluoromethanesulfonic Acid
Aqueous trifluoromethanesulfonic acid has been used to cleave a triethylsilyl ether with
high selectivity, as in the conversion of 30 into the calicheamicinone precursor 31
(Scheme 15). [44] Neither the tert-butyldimethylsilyl ether nor any other acid-sensitive functionality
was compromised in this process.
Scheme 15 Cleavage of Triethylsilyl Ethers with Trifluoromethanesulfonic Acid [44]
BocO
Boc2N
TBDMSO O
30
OTES
FOR PERSONAL USE ONLY
382 Science of Synthesis 4.4 Silicon Compounds
TfOH, H2O, THF, rt
95%
BocO
Boc2N TBDMSO O
10-[Bis(tert-butoxycarbonyl)amino]-11-(tert-butoxycarbonyloxy)-1-(tert-butyldimethylsiloxy)-8â-hydroxybicyclo[7.3.1]trideca-4,9,11-triene-2,6-diyn-13-one
(31): [44]
To a soln of 30 (906 mg, 1.17 mmol) in THF (10.6 mL) under argon at rt was added dropwise
a soln of TfOH (1.37 mL) in H 2O (3.87 mL) by cannula with stirring. The mixture was stirred
for 10 min, diluted with Et 2O (50 mL), and washed with sat. aq NaHCO 3 (20 mL). After drying
(MgSO 4) and evaporation of the solvents in vacuo, the product was purified by chromatography
(silica gel, Et 2O/hexanes 2:8) to give 31; yield: 730 mg (95%).
4.4.17.2.4 Method 4:
Cleavage ofTriethylsilyl Ethers with Tetrabutylammonium Fluoride
Triethylsilyl ethers are appreciably more stable to basic reagents than trimethylsilyl
ethers and will survive conditions such as potassium carbonate in methanol; [41] however,
they are readily cleaved with tetrabutylammonium fluoride in tetrahydrofuran. The rate
of cleavage with this reagent is sufficiently rapid such that a triethylsilyl group can be removed
without perturbing a more resistant ether, such as a tert-butyldiphenylsilyl ether.
This is illustrated in the selective cleavage of the triethylsilyl ether in 32 to give alcohol
33, in which the tert-butyldiphenylsilyl ether as well as the 4-methoxybenzyl ether are retained
(Scheme 16). [45]
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG
31
OH