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O
R
2
OH
R
2
R
1
O
N
2
O
O
B
H
+
Rh(II)
B
N
A
R
2
N
A
N
A=B
R
1
n
O
R
1
n
n
Nuc
Nuc
Nuc
27
28
29
SCHEME 13.7
R
2
CH
2
O
CO
2
Et
( )
n
R
2
O
HO
EtO
2
C
( )
n
O
( )
n
N
R
1
N
2
BF
3
•OEt
2
Rh(II)
R
1
R
1
N
O
N
R
2
CO
2
Et
OMe
O
OMe
OMe
OMe
OMe
OMe
30
(R
1
=R
2
=H;
n
=2)
31
(R
1
=H; R
2
=CH
3
;
n
=1)
32
(R
1
=CH
3
; R
2
=H;
n
=1)
33
(R
1
=R
2
=H;
n
=2, 98%)
34
(R
1
=H; R
2
=CH
3
;
n
=1, 95%)
35
(R
1
=CH
3
; R
2
=H;
n
=1, 90%)
36
(R
1
=R
2
=H;
n
=2, 97%)
37
(R
1
=H; R
2
=CH
3
;
n
=1, 95%)
38
(R
1
=CH
3
; R
2
=H;
n
=1, 85%)
SCHEME 13.8
B-ring homologues of the erythrinane family of alkaloids. By starting from simple
acyclic diazoimides
27
, the Padwa group has established a tandem cyclization/
cycloaddition/cationic
-cyclization protocol as a method for the construction of
complex nitrogen polyheterocycles of type
29
.
The first example of such a process involved the treatment of diazoimides
30
-
32
with a catalytic amount of rhodium(II) perfluorobutyrate in CH
2
Cl
2
at 25
C that
provided cycloadducts
33
(98%),
34
(95%), and
35
(90%) (Scheme 13.8). Formation
of the
endo
-cycloadduct with respect to the carbonyl ylide dipole in these cycloaddi-
tions is in full accord with molecular mechanics calculations, which show a large
energy difference between the two diastereomers. When the individual cycloadducts
were exposed toBF
3
p
OEt
2
(2 equiv) inCH
2
Cl
2
at 0
C, the cyclized products
36
(97%),
37
(95%), and
38
(85%) were isolated as single diastereomers. The
cis
stereo-
chemistry of the A/B ring junction for
36-38
was assigned by analogy to similar
erythrinane products obtained via a Mondon-enamide-type cyclization [12-16] and
was unequivocally verified by an X-ray crystal analysis of all three cycloadducts.
In all the three cases, the
anti
stereochemical relationship is still maintained between
the hydroxyl stereocenter (from the oxygen bridge) and the bridgehead proton
(R
2
H) or methyl (R
2
CH
3
) group.
When the dipolar cycloadduct
40
derived from the unsubstituted alkenyl
diazoimide
39
was exposed to BF
3
¼
¼
OEt
2
, the resulting cyclized product
41
(90%)
was identified as the all
syn
tetracyclic lactam by an X-ray crystal analysis
(Scheme 13.9). Thus, in contrast to the other three systems, the bridgehead proton
of
41
lies
syn
to the hydroxyl stereocenter of the original cycloadduct. It is assumed
that the intermediate
N
-acyliminium ions formed from the Lewis acid-assisted ring
opening of the isomunchnone cycloadducts undergo rapid proton loss to produce
tetrasubstituted enamides. A subsequent acid-induced cyclization then occurs from
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