Silyl Ethers - Thieme Chemistry

Tri-tert-butyl {1S-[1á,3á,4â,5á,6á(2E,4S,6S),7â]}-4-Hydroxy-6-(1-oxo-4,6-dimethyloct-2enyloxy)-1-(3-oxopropyl)-7-(triethylsiloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate
(21): [38]
Alcohol 20 (48.2 mg, 71.9 ìmol) was dissolved in pyridine (2.5 mL), and the soln was
cooled to 08C. A soln of TESCl (0.40 mL, 2.4 mmol) in pyridine (2.0 mL) was added over
5 min, after which the ice bath was removed and the soln was stirred at rt for 22 h. The
mixture was diluted with Et 2O (30 mL) and was washed with 0.5 M HCl (2 ” 30 mL), sat. aq
NaHCO 3 (20 mL), H 2O (20 mL), and brine (20 mL). The aqueous layers were back-extracted
with Et 2O (30 mL), and the combined organic layers were dried (MgSO 4), filtered, and
evaporated. The crude product was purified by flash chromatography (silica gel, gradient
elution, EtOAc/hexanes 1:7 to 1:5) to give 21; yield: 46.3 mg (82%).
4.4.17.2.1.2 Variation 2:
With Chlorotriethylsilane in the Presence of4-(Dimethylamino)pyridine
Chlorotriethylsilane together with 4-(dimethylamino)pyridine is often used for the silylation
of sterically hindered secondary alcohols. [36] This combination with imidazole in dichloromethane
at low temperature was effective in promoting a selective silylation of
one of the two secondary alcohols in compound 22 to yield the mono(triethylsilyl ether)
23 (Scheme 11). [39] This selectivity, which was critical to a subsequent internal ketalization
involving the free hydroxy group of 23, reflects the subtle steric factors that can impinge
upon and differentiate the reactivity of cyclic and acyclic alcohols toward this silylating
agent.
Scheme 11 Silylation with Chlorotriethylsilane in the Presence of 4-(Dimethylamino)pyridine
[39]
O
OH
O O O
H H H O O
HO MeO
22
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 379
O
TESCl, DMAP, imidazole
CH2Cl2, −78 oC, 3 h
98%
OTES
O O O
H H H O O
HO MeO
(2S,2¢R,2¢¢R,3¢¢R,4¢¢R,5¢S,5¢¢S)-5¢¢-[(1R,2R,3S,4R)-1-Hydroxy-3-methoxy-2-methyl-4-(2-methyl-
1,3-dioxolan-2-yl)pentyl]-2,3¢¢,5¢-trimethyl-4¢¢-(triethylsiloxy)decahydro-2,2¢:5¢,2¢¢-terfuran-5(2H)-one
(23): [39]
To a soln of alcohol 22 (210 mg, 420 ìmol) in CH 2Cl 2 (8.4 mL) at ±788C were added imidazole
(71 mg, 1.05 mmol), DMAP (10 mg), and TESCl (78 ìL, 70 mg, 462 ìmol). After 3 h at
±78 8C, the mixture was quenched by the addition of sat. aq NaHCO 3 (5 mL), and warmed
to rt. The mixture was poured into EtOAc (25 mL) and then sat. aq NaHCO 3 (25 mL). The
phases were separated, and the aqueous layer was extracted with EtOAc (2 ” 25 mL). The
combined organic layers were dried (Na 2SO 4), filtered, and concentrated in vacuo. Purification
by flash chromatography (EtOAc/hexane 45:55) afforded 23 as a clear oil; yield:
253 mg (98%).
23
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG