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