Silyl Ethers - Thieme Chemistry

4.4.17.4.1.1 Variation 1:
With Triisopropylsilyl Trifluoromethanesulfonate
in the Presence of4-(Dimethylamino)pyridine
As with other silylating agents, triisopropylsilyl trifluoromethanesulfonate becomes
more reactive when used in the presence of 4-(dimethylamino)pyridine, especially when
pyridine is the solvent. Under these conditions, secondary alcohols are converted into
their triisopropylsilyl ethers rapidly and in high yield. The silylation of diol 72 to give
the tris(silyl ether) 73 illustrates this increased reactivity of the silylating agent (Scheme
36). [80]
Scheme 36 Silylation of Secondary Alcohols with Triisopropylsilyl Trifluoromethanesulfonate
[80]
TBDPSO
HO
HO
H
O
72
O
O
O
O
TBDPSO
TIPSO
TIPSOTf
DMAP, py, rt, 15 h
99%
TIPSO
(1S,1¢S,3R,5S,5¢S,6S,6¢S)-8-[(1S,3R)-4-(tert-Butyldiphenylsiloxy)-1,3-bis(triisopropylsiloxy)butyl]-5,5¢-dimethyl-8¢-oxo-3,3¢-spirobi(2,7-dioxabicyclo[4.3.0]nonane)
(73): [80]
Diol 72 (125 mg, 0.200 mmol) was combined with DMAP (44 mg, 0.36 mmol) under a N 2
atmosphere and then dissolved in dry pyridine (0.6 mL). TIPSOTf (0.4 mL, 1.49 mmol) was
added via syringe, and the mixture was stirred for 15 h. Excess TIPSOTf was consumed by
the addition of dry MeOH (1.5 mL). After 15 min, the reaction was transferred to a separatory
funnel with Et 2O and washed first with 5% HCl (15 mL) and then with a mixture of sat.
aq NaHCO 3 and brine (1:1, 20 mL). The aqueous layers were extracted with Et 2O
(2 ” 40 mL), and the combined organics were dried (MgSO 4). Filtration through a short silica
gel plug with additional Et 2O, and concentration in vacuo provided the crude, fully protected
lactone which was purified by chromatography (silica gel, Et 2O/hexanes 1:3) to afford
73 as a pale yellow oil; yield: 187 mg (99%).
Cleavage
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 397
4.4.17.4.2 Method 2:
Cleavage ofTriisopropylsilyl Ethers with
Tetrabutylammonium Fluoride
The most general method for cleavage of a triisopropylsilyl ether is with tetrabutylammonium
fluoride, however, this reagent typically exhibits no selectivity between silyl ethers
of this class that are situated in different structural environments. Nevertheless, it is possible
to retain a triisopropylsilyl ether while a more susceptible silyl ether, including a
secondary tert-butyldiphenylsilyl ether, is cleaved with this reagent (see Scheme 48, Section
4.4.17.5.4). The conventional protocol for removing a triisopropylsilyl ether is illus-
H
O
73
O
O
O
O
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG