Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

592 NITRONATES
O
N
O
+
D
O
N
O
259
D
Scheme 3.172
A
A
A
O
*
N O
*
*
260
H 2; Ni/Ra
OH HO
*
NH2
*
A
*
D
target products
(C=C–D) are most efÞcient in the former process, whereas electron-deÞcient
oleÞns (C=C–D) are most efÞcient in the latter process. Hence, the [4 + 2]-cycloaddition
of alkene C=C–D with α-nitroalkene can be successfully performed in
the presence of alkene C=C–A. In this step, an auxillary is introduced into the
resulting nitronate (259) and, if required, enantiomerically pure nitronate (259)
is isolated. Then the [3 + 2]-cycloaddition reaction of nitronate (259) with oleÞn
C=C–A is performed to obtain nitroso acetal (260), which is generally followed
by reduction of the nitroso acetal fragment. The conÞgurations of the labeled
stereocenters generated in the tandem process are retained during the reduction
process. The resulting intermediate A is transformed into the target product by
using standard manipulations of organic synthesis.
When choosing a concrete scheme for the synthesis of a complicated substrate
in terms of the strategy proposed by Prof. Denmark, not only the characteristic
features of the target product but also other factors should be taken into account.
As a rule, intramolecular cycloaddition reactions proceed more easily and are
characterized by higher stereoselectivity, but the starting substrates are much
more difÞcult to synthesize.
A representative series of enantiomerically pure alkaloids and other compounds
having known biological activity was synthesized using the above
described strategy by the group of Prof. Denmark (Chart 3.19).
As mentioned above, not only general principles but also concrete examples
of the use of the tandem strategy by Prof. Denmark were considered in two
monographs (427, 428). These data should be supplemented by the synthesis of
azafenestranes, which has been recently performed by Prof. Denmark and his
group (429, 430) (Scheme 3.173).
The cis,cis,cis,cis-[5,5,5,5]-1-azafenestrane as complex with BH3 (261) was
prepared starting from nitroalkene (262), which is difÞcult to synthesize, using
an approach shown in Chart 3.18 and Scheme 3.172. (429)
D