Silyl Ethers - Thieme Chemistry

(2Z,4S,5R,6E,8S,9R,10S,12S,13R)-5-(tert-Butyldimethylsiloxy)-13-[3-(2,5-dimethyl-1H-pyrrol-1-yl)-2,5-dimethoxyphenyl]-9,10,13-trimethoxy-4,6,8,12-tetramethyltrideca-2,6-dien-
1-ol (65): [70]
A soln of bis(silyl ether) 64 (42 mg, 0.051 mmol) in THF (2 mL) containing TFA/H 2O (9:1,
400 ìL) was stirred at 08C for 3 h. Sat. NaHCO 3 (5 mL) was added, and the mixture was extracted
with Et 2O (3 ” 10 mL). The combined organic layers were dried (MgSO 4) and concentrated
under reduced pressure; the residue was purified by flash chromatography
(hexanes/EtOAc 3:1) to give alcohol 65 as a colorless, viscous oil; yield: 33 mg (91%).
(3aR,4R,5S,7aS)-7a-(tert-Butyldimethylsiloxy)-5-hydroxy-4-(hydroxymethyl)-4-methyl-
3a,4,5,7a-tetrahydroisobenzofuran-1(3H)-one (67): [71]
A soln of alcohol 66 (43.9 g, 99 mmol) in CH 2Cl 2 (250 mL) and MeOH (20 mL) was treated
with CSA (0.52 g, 2.24 mmol) and stirred at 258C for 1 h. After dilution with CH 2Cl 2
(300 mL), the reaction was quenched with aq NaHCO 3 (150 mL). The organic layer was separated,
and the aqueous layer was extracted with Et 2O (2 ” 200 mL). The combined organic
layer was dried (Na 2SO 4), concentrated, and purified by flash chromatography (silica gel,
Et 2O/petroleum ether 1:1) to give diol 67 as white crystals; yield: 32.6 g (100%).
4.4.17.3.6.4 Variation 4:
With Lewis Acids
Lewis acids have found limited use as reagents for cleaving silyl ethers, in part because
they coordinate weakly with the oxygen atom of ethers of this class; however, they can
sometimes effect a remarkably efficient cleavage of a tert-butyldimethylsilyl ether, [72] as
in the conversion of silyl ether 68 into alcohol 69 with boron trifluoride±diethyl ether
complex (Scheme 34). [73] A noteworthy feature of this transformation is that the trisubstituted
epoxide of 68 does not suffer rearrangement to a ketone under the reaction conditions.
Scheme 34 Cleavage of a tert-Butyldimethylsilyl Ether with Boron Trifluoride±Diethyl
Ether Complex [73]
O
BnO
H
H
68
O
O
OTBDMS
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 395
BF3 OEt2, CH2Cl2
0−10 oC 92%
(4aá,8aá,9aá)-1á-Benzyloxy-6á-hydroxy-4á,6aâ,7aâ,9bâ-tetramethyldodecahydrophenanthro[2,3-b]oxirene-2,7-dione
(69): [73]
To a soln of silyl ether 68 (53 mg, 0.10 mmol) in dry CH 2Cl 2 (8 mL) was added BF 3 ·OEt 2
(63 ìL, 0.50 mmol) at 08C under N 2. The mixture was allowed to warm to ca. 108C and
was then stirred for 6 h. The reaction was quenched with sat. aq NH 4Cl (2 mL), and the
aqueous phase was extracted with CH 2Cl 2 (3 ” 10 mL). The combined organic extracts
were washed with brine (2 mL), dried (MgSO 4), and filtered. Concentration of the filtrate
followed by flash column chromatography (hexane/EtOAc 7:1) gave alcohol 69 as a white
solid; yield: 38 mg (92%).
O
BnO
H
69
H
O
OH
O
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG