Silyl Ethers - Thieme Chemistry

(4S,6R)-4-[(1R,2S,3E)-2-{[1-(tert-Butoxycarbonyl)-2-piperidyl]carbonyloxy}-4-[(1R,3R,4R)-4-
(tert-butyldiphenylsiloxy)-3-methoxycyclohexyl]-1,3-dimethylbut-3-enyl]-11-[(1E,4S,6S)-6-
{(2R,3S,5R,6R)-6-[(1S)-1,2-dihydroxyethyl]-3-methoxy-5-methyltetrahydropyran-2-yl}-6methoxy-2,4-dimethylhex-1-enyl]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-10-en-9-one
(51): [57]
To a soln of bis(tert-butyldimethylsilyl ether) 50 (879 mg, 0.61 mmol) in THF (15 mL) was
added 1 M TBAF in THF (1.84 mL, 1.84 mmol). After 2 h, the reaction was quenched with
NH 4Cl, and the THF was removed in vacuo. The product was extracted into EtOAc, and
the organic extracts were dried (MgSO 4), filtered, and concentrated in vacuo. The residue
was chromatographed (silica gel, 20±50% EtOAc/hexanes) to give diol 51; yield: 525 mg
(71%).
(3S,6R,7S,12Z,15S,16E)-3,7-Bis(tert-butyldimethylsiloxy)-15-hydroxy-4,4,6,16-tetramethyl-
17-(2-methyl-1,3-thiazol-4-yl)-5-oxoheptadeca-12,16-dienoic Acid (53): [58]
A soln of tris(tert-butyldimethylsilyl ether) 52 (300 mg, 0.36 mmol) in THF (7.0 mL) at 258C
was treated with 1 M TBAF in THF (2.2 mL, 2.2 mmol, 6.0 equiv). After being stirred for 8 h,
the mixture was diluted with EtOAc (10 mL) and washed with 1 M aq HCl (10 mL). The
aqueous soln was extracted with EtOAc (4 ” 10 mL), and the combined organic phase was
washed with brine (10 mL), dried (MgSO 4), and concentrated. The crude mixture was purified
by flash column chromatography (silica gel, MeOH/CH 2Cl 2 5:95) to provide hydroxy
acid 53 as a yellow oil; yield: 203 mg (78%).
4.4.17.3.5 Method 5:
Cleavage of tert-Butyldimethylsilyl Ethers with
Tris(dimethylamino)sulfur (Trimethylsilyl)difluoride
Tris(dimethylamino)sulfur (trimethylsilyl)difluoride (TASF) [59] is a source of fluoride ion
that is sometimes more effective than tetrabutylammonium fluoride (Section 4.4.17.3.4)
for removing silyl ethers, [60] especially where the basicity associated with the latter reagent
presents a problem. Thus, cleavage of the tert-butyldimethylsilyl ether 54 with
tris(dimethylamino)sulfur (trimethylsilyl)difluoride gives the taxol precursor 55 in high
yield (Scheme 27), whereas exposure of 54 to tetrabutylammonium fluoride results in
cleavage of the benzoate as well as the silyl group. [61] Attempts to cleave the silyl ether of
54 with hydrogen fluoride±pyridine complex led to products of rearrangement.
Scheme 27 Cleavage of a tert-Butyldimethylsilyl Ether with Tris(dimethylamino)sulfur
(Trimethylsilyl)difluoride [61]
TBDMSO
AcO
HO
BzO
AcO
54
FOR PERSONAL USE ONLY
390 Science of Synthesis 4.4 Silicon Compounds
O
OBOM
O
TASF, THF, rt, 1 h
94%
HO
AcO
HO
BzO
AcO
55
O
OBOM
7-O-(Benzyloxymethyl)baccatin III (55): [61]
A soln of silyl ether 54 (16.3 mg, 19.9 ìmol) in THF (0.5 mL) was added to TASF (37 mg,
0.134 mmol) at rt under a N 2 atmosphere. The mixture was stirred for 1 h, diluted with
EtOAc, poured into sat. aq NaHCO 3 (20 mL) and extracted with CHCl 3 (3 ” 30 mL). The combined
organic phase was dried (Na 2SO 4) and concentrated under reduced pressure to give
a pale yellow oil (16 mg), which was filtered through a pad of silica gel using EtOAc/hexane
(7:3) as eluent. The filtrate was concentrated to give diol 55; yield: 13.5 mg (94%).
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG
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