Chemistry Reference
In-Depth Information
Fig. 8.14
Phenyl is an acid-labile protecting group for the silanediols
also a classic electrophilic aromatic substitution reaction, promoted by the ability
of silicon to stabilize a β-cation (
56
), and the reactivity of the aromatic ring can be
altered by ring substitution [
60
,
61
]. Use of diphenylsilyl as a silanediol precursor
turned out to be a fortuitous choice because of the importance of phenyl groups in
the formation and stabilization of silane anions (see Fig.
8.23
) [
62
,
63
]. Studies
suggest that the amide groups flanking the diphenylsilane participate in the loss of
phenyl, presumably by attacking the protonated arylsilane
56
, Fig.
8.14
. In cases
without amides on both sides of the silane, loss of the second phenyl group is slower
and more difficult [
64
]. Triflic acid has been routinely used for this deprotection
step, but recently methods employing the much milder trifluoroacetic acid have
been enumerated [
61
].
8.4.3
An HIV Protease Inhibitor
HIV protease inhibitor
44
(Fig.
8.12
) was prepared in enantiomerically pure form
by addition of two equivalents of an optically pure lithium reagent to a dichlorosi-
lane. Starting with the Evans chiral auxiliary
58
and alkylation of the titanium eno-
late with BOMCl, Fig. 15, reductive cleavage of the auxiliary and conversion of the
resulting alcohol to an iodide gave
59
(76 % for 3 steps). Metal-halogen exchange
followed by addition of 0.45 equivalents of diphenyldichlorosilane gave
60
in 99 %
yield. Cleavage of the benzyl ethers and a two-stage oxidation of the resulting diol
gave the diacid (84 %). Coupling of this diacid with commercially available amino
alcohol
62
using diethylphosphoryl cyanide gave diamide
61
(75 %). The critical
deprotection of diphenylsilane
61
to give the diol
44
was carefully studied with
regard to cleavage of both silicon-phenyl bonds and isolation of monomer
44
. Pure
44
was most easily isolated by precipitation, in 37 % yield [
48
].
