Silyl Ethers - Thieme Chemistry

Scheme 39 Cleavage of a Triisopropylsilyl and a tert-Butyldimethylsilyl Ether with Hydrogen
Fluoride±Pyridine Complex [82]
TIPSO
MeO
O
HO
N
O
O
O
MeO
O
FOR PERSONAL USE ONLY
400 Science of Synthesis 4.4 Silicon Compounds
79
O
TBDMSO
OMe
O
HO
MeO
HF py, py, THF
0 oC to rt, 48 h
69%
O O HO
(±)-Rapamycin (80): [82]
At 0 8C a soln of synthetic hemiketal (±)-79 (5.1 mg, 4.3 ìmol) in THF (0.5 mL) was treated
with pyridine (0.5 mL) followed by HF·pyridine (0.5 mL). The mixture was warmed to rt,
stirred for 48 h, and then partitioned between Et 2O (10 mL) and H 2O (10 mL). The organic
phase was washed with sat. aq CuSO 4 (5 mL), sat. aq NaHCO 3 (5 mL), H 2O (5 mL), and brine
(5 mL), dried (MgSO 4), filtered, and concentrated. Flash chromatography (hexanes/EtOAc
1:1 then 1:3) provided synthetic rapamycin (80) as a clear oil; yield: 2.7 mg (69%). Recrystallization
(acetone/hexanes 4:6) gave (±)-80 as a white solid.
(−)-80
4.4.17.4.5 Method 5:
Cleavage ofTriisopropylsilyl Ethers under Acidic Conditions
Although acidic conditions are not often used to cleave triisopropylsilyl ethers, available
evidence suggests that silyl ethers of this class are quite susceptible to cleavage in the
presence of acidic reagents. [76,83] Thus, the triisopropylsilyl blocking group was removed
from the mycotrienin precursor 81 with 4-toluenesulfonic acid in methanol to yield alcohol
82 without affecting the adjacent tert-butyldimethylsilyl ether (Scheme 40). [84] The
sensitive triene unit of 81 was also stable under these conditions.
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG
OMe
O