Silyl Ethers - Thieme Chemistry

Scheme 22 Selective Silylation of Secondary Alcohols with tert-Butyldimethylsilyl Trifluoromethanesulfonate
[54]
HO
HO OH
H
H
TBDMSOTf, Et3N
DMAP, CH2Cl2 −20
87%
oC, 30 min
TBDMSO
44 45
HO OTBDMS
H
(1á,3â,4aá,5á,8â,8aá)-8-(tert-Butyldimethylsiloxy)-3-(tert-butyldimethylsiloxymethyl)-5isopropyl-3-methyldecahydro-1-naphthol
(45): [54]
To a stirred mixture of triol 44 (92 mg, 0.36 mmol), Et 3N (109 mg, 1.08 mmol), and DMAP
(2 mg, 0.016 mmol) in CH 2Cl 2 (5 mL) at ±20 8C, was added TBDMSOTf (190 mg, 0.72 mmol).
The mixture was stirred at ±208C for 30 min, diluted with Et 2O (40 mL), washed with 5%
HCl (2 mL), brine (5 mL) and H 2O (5 mL), dried (Na 2SO 4), and concentrated in vacuo. Flash
chromatography of the residue (silica gel, EtOAc/hexane 5:95) afforded 45 as a colorless
oil; yield: 152 mg (87%).
4.4.17.3.3 Method 3:
Migration ofa tert-Butyldimethylsilyl Group from
a tert-Butyldimethylsilyl Ether to an Alcohol
The tert-butyldimethylsilyl group of a tert-butyldimethylsilyl ether will migrate to the oxygen
atom of an adjacent alcohol under basic conditions if the new tert-butyldimethylsilyl
ether is sterically less crowded than its precursor. [14] Thus, the direction of migration is
invariably from a secondary to a primary alcohol or from a tertiary to either a secondary
or primary alcohol. Migration between 1,2-substituted and 1,3-substituted diol derivatives
is particularly common, although transfer of a tert-butyldimethylsilyl group between
oxygens that span four or more carbons can occur if the oxygens are in spatial
proximity. [16] The mechanism usually envisioned for these migrations involves intramolecular
attack by an alkoxide oxygen on silicon to produce a pentacoordinate intermediate
that collapses toward the more thermodynamically stable tert-butyldimethylsilyl
ether. While silyl migration between oxygen atoms can pose an inconvenience in certain
polyhydroxylated systems such as carbohydrates, where site-specific silylation may be desired,
a virtue can be made of this chemistry in the deprotection of a silyl ether that may
be difficult to cleave. Thus, if the silyl group can be forced to move to a less sterically
crowded oxygen, its cleavage can become more facile.
An example of an efficient migration of a tert-butyldimethylsilyl group is seen in the
rearrangement of secondary tert-butyldimethylsilyl ether 46 to its isomeric primary silyl
ether 47 (Scheme 23). [55]
Scheme 23 Rearrangement of a Secondary tert-Butyldimethylsilyl Ether
to a Primary tert-Butyldimethylsilyl Ether [55]
OTBDMS
F3C OH
46
FOR PERSONAL USE ONLY
4.4.17 Silyl Ethers 387
t-BuOK, THF/DMF (1:4)
−78 oC, 4 h
99%
OH
47
H
F 3C OTBDMS
Another example, in this case involving migration of the tert-butyldimethylsilyl group
from a tertiary to a secondary alcohol, occurred in the course of an approach to the core
structure of esperamicin A. [56] The rearrangement was triggered by S,S-diphenylsulfil-
for references see p 410
White, J. D.; Carter, R. G., SOS, (2002) 4, 371. 2002 Georg Thieme Verlag KG