Biomedical Engineering Reference
In-Depth Information
13.3.
1,2-AMMONIUM YLIDES
13.3.1. [1,2]-Rearrangements (the Stevens Rearrangement)
In 1928, Stevens and coworkers described an unexpected rearrangement of ammo-
nium salt
325
upon exposure to dilute aqueous NaOH, providing
326
in 90% yield
(Scheme 13.61) [107]. Since this discovery, the reaction, commonly referred to as the
Stevens rearrangement, has been developed and applied to the synthesis of a variety of
nitrogenous natural products. The reaction has been reviewed several times [108], and
ion pair, concerted [1,2]-shift, and radical pair mechanisms have been proposed.
West and Vanecko have been particularly active in researching the application
of the Stevens rearrangement to natural product synthesis. For example, the catalytic
decomposition of a diazo azetidine
327
by Cu(acac)
2
in toluene at reflux afforded a
mixture (3.6:1) of pyrrolizidines
328
and
329
in 82% yield (Scheme 13.62) [109].
Catalytic hydrogenation of the
328
/
329
mixture afforded a separable mixture of
330
and
331
in 88% and 71% yields, respectively, based on the ratio of
328
:
329
. LiAlH
4
-
mediated reduction of
330
and
331
gave (
)-turneforcidine and (
)-platynecine in
91% and 94% yields, respectively.
One of the interesting discoveries to come from this research is the migratory
selectivity of the intermediate ammonium ylide; the strain of the azetidine drives ring
expansion as the only observed reaction pathway, even with groups capable of better
stabilizing a radical (i.e., Bn) attached to the nitrogen. A subsequent study explored
O
Br
-
O
N
aq NaOH
N
90%
325
326
SCHEME 13.61
CO
2
Me
O
O
MeO
2
C
MeO
2
C
Cu(acac)
2
H
H
+
N
PhCH
3
reflux
82%
N
2
N
N
O
327
328
329
O
H
2
PtO
2
O
OH
MeO
2
C
H
H
+
N
N
331
(71%)
330
(88%)
LiAlH
4
THF
LiAlH
4
THF
94%
91%
HO
HO
OH
OH
H
H
N
N
(±)-Platynecine
(±)-Turneforcidine
SCHEME 13.62
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