Chemistry Reference
In-Depth Information
R
R
O
HTIB
CH
3
CN
OMe
or
OMe
SO
2
HN
0°C, rt
20 min
N
N
OMe
OMe
N
SO
2
SO
2
SO
2
353
354
355
(86%)
356
(66%)
SCHEME 10.55.
literature reveals that in many of the hydroxamate substrates from which spirolac-
tams are generated, the arene has a longitudinal plane of symmetry and, as a result,
dearomatization leads to the formation of a chirotopic nonstereogenic quaternary
center.
137
If, however, the aromatic ring is substituted in a way that breaks this
symmetry then the
-faces become heterotopic and a new quaternary stereogenic
center is formed upon cyclization. In this context, Wardrop
et al.
have investigated
the effect of side stereocenters upon
p
p
-facial selectivity during the spirocyclization
(Scheme 10.56).
128
In this case, it was anticipated that cyclization of
of nitrenium ion
357
357
would preferentially proceed
358
z
being
disfavored due to nonbonding interactions (benzylic strain)
138
between the substit-
uents on the side-chain and the
ortho
position of the aromatic ring.
139
Indeed,
consistent with this model, in all cases studied, the
anti
isomers were found to be the
predominant products with selectivities ranging from modest (Table 10.8, entry 9) to
excellent (entries 1, 3, and 5).
359
z
to form
anti-
via a transition state resembling
361
, conformer
R
1
H
R
2
R
1
H
R
2
R
2
R
3
R
3
R
1
O
O
N
N
O
N
MeO
OMe
MeO
R
3
MeO
OMe
OMe
358
(disfavored)
359
(favored)
357
R
2
R
2
R
1
H
R
1
H
R
3
R
3
O
O
N
MeO
N
MeO
O
O
syn
-
360
anti-
361
SCHEME 10.56.
