Chemistry Reference
In-Depth Information
Fig. 8.20
Asymmetric intra-
molecular hydrosilylation
sets stereochemistry with
high ee
and methallyl alcohol (R = methyl), Fig.
8.18
, gives silyl ether
79
. Treatment of
this with a variety of metals will induce cyclization and formation of silafuran
89
[
75
,
76
]. When rhodium is used with (
S, S
)-ethylferrotane [
77
] as a ligand, this
cyclization sets the stereogenic center in
89
with good to excellent enantioselec-
tivity [
78
].
One path to convert these silafurans to protease inhibitor structures involves
opening of the ring with aqueous HF and protecting the resulting alcohol to give
94
[
78
]. These fluorosilanes react readily with nucleophiles and can also be converted
into nucleophilic silyllithium reagents [
70
]. An even more efficient conversion of
94
to protease inhibitor structures is described in Fig.
8.23
.
8.5.2 α-Alkyl-α-Amino Silanes
8.5.2.1
Asymmetric Reduction of a Silyl Ketone
Construction of the α-amino silanes component of the silanediol
46
with the
correct stereochemistry was initially done by separation of diastereomers, fol-
lowing reduction of a silyl ketone without stereocontrol and displacement of the
alcohol with phthalimide, Fig.
8.17
. A better solution was to control the ketone
reduction, and this has been done in the case of
95
with stoichiometric use of
the CBS-borane complex, Fig.
8.21
. Mitsunobu inversion then gave the desired
stereochemistry (
97
). Oxidative cleavage of the alkene then completes the se-
quence [
79
].
