Chemistry Reference
In-Depth Information
O
R
R
Yield
dr
OMe
H
H
O
H
65%
2.6:1
N
OH
CF
3
85%
98:2
OMe
R
609
610
MeO
O
MeO
OMe
H
H
+
O
N
HO
N
O
OR
OMe
OMe
OMe
612
(21/54%; R = H))
(24/0%
a
)
613
611
TFA
(R = TFA)
MeO
H
+
PMP
MeO
N
+
N
O
H
N
O
MeO
O
+
OMe
OMe
a
yield w/o tfa
614
615
616
SCHEME 10.99.
617d
, or via steric effects, both proximal and distal, as observed with
617e
,
617f
,
and
.
That the regioselectivity of hydroxamate aziridinium ion ring opening can be
effectively controlled through substituent effects is further apparent by the regio-
chemically divergent oxamidation of diastereomers
617g
620
and
623
(Scheme 10.100).
The exclusive formation of 6-azabicyclo[2.2.2]octane
620
suggests that electron-withdrawing groups, such as
O
-acetyl groups, have a inhibi-
tory effect on the proximal ring opening of aziridinium ions.
221
Cyclization of
trans
-
623
622
from
cis
-substituted
in which the
O
-acetoxy group, now positioned in an
endo
orientation is able to participate in the ring opening of the neighboring aziridinium
ion to generate 1,3-dioxenium ion
generates
624
625
and thus establish the 6-azabicyclo[3.2.1]
octane skeleton.
222
Regioselective hydrolysis of this intermediate then leads to
626
and accounts for the 1,2-acetyl migration observed in this product.
The
a
-hydroxymethyl piperidine subunit available through the oxamidation of
hexenohydroxamates (Table 10.13, entry 3) is a ubiquitous structural motif found in a
range of pharmacologically active alkaloids, such as (
)-quinine, and numerous
iminosugar glycosidase inhibitors, including nojirimycin. (
)is
among the simplest natural product to bear this structural motif and consequentially
has proven to be a popular target with which to evaluate new methodologies for the
stereocontrolled formation of 1,2-amino alcohols.
223
รพ
)-
a
-Conhydrine (
629
