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O
EtO
2
C
O
EtO
2
C
R
O
O
R
R
Cu(acac)
2
N
OEt
N
N
PhMe
N
2
n
n
n
358a
(
n
= 0; R = H)
358b
(
n
= 1; R = H)
358c
(
n
= 1; R = Me)
360a
(
n
= 0; R = H)
360b
(
n
= 1; R = H)
360c
(
n
= 1; R = Me)
359a
(
n
= 0; R = H)
359b
(
n
= 1; R = H)
359c
(
n
= 1; R = Me)
SCHEME 13.67
the use of amido nitrogens in this particular step [118]. In a simple model system, the
Rh
2
(OAc)
4
-catalyzed decomposition of diazoamide
361
(R
Et, Me, Ph, Bn) at 80
C
in benzene failed to produce the desired product
362
(Scheme 13.68). Rather, it was
determined through a series of trapping experiments that the amido oxygen interacted
with the metallocarbenoid to produce highly reactive isobenzofurans. Undeterred by
these results, diazoamide
363
was exposed to catalytic amounts of Rh
2
(OAc)
4
producing
364
in 83% yield. Similarly,
365
afforded
366
in 75% yield under the
same conditions. It is unclear why
363
and
365
underwent [1,2]-rearrangement while
361
failed to do so.
An approach to the isopavine alkaloids featuring a rearrangement of azocine
structures produced a series of morphinomimetic compounds. In this study, Hanessian
and Mauduit reacted azocines of the general structure
367
(R
¼
Me,
i
-Pr,
i
-Bu, Bn,
etc.) with methyl iodide that gave the ammonium iodides
368
(Scheme 13.69) [119].
Heating a solution of
368
to 80
C with
t
-BuOK produced isopavines
369
in 65-88%
yield. The stereoselectivity of the rearrangement is remarkable and was rationalized
by examining the possible ring-opened intermediates
¼
370a
and
370b
in the
O
R
O
N
Rh
2
(OAc)
4
R
R
N
N
2
R
CO
2
Me
CO
2
Me
361
362
O
O
N
N
2
N
Rh
2
(OAc)
4
83%
CO
2
Me
CO
2
Me
363
364
OMe
O
O
OMe
O
N
N
Rh
2
(OAc)
4
O
N
2
CO
2
Me
75%
CO
2
Me
O
365
366
O
SCHEME 13.68
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