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

OH NO 2
R EtO2CN NCO 2Et
PPh 3, benzene
O N
SYNTHESIS OF NITRONATES 449
5
13
R = Ph (yield for 5 = 98%); SO2Ph (yield for 5 = 15%; for 13 = 82%)
Scheme 3.17
primary AN RCH2NO2 to give in situ ylides A, which undergo cyclization to
the corresponding nitronates 5. The chemoselectivity of this reaction is also low
and it is accompanied by generation of isomeric cyclopropanes (13).
The process shown in Scheme 3.16 is rather interesting. It should be noted
that in most cases this reaction is very stereoselective with respect to the arrangement
of the substituents at C-4 and C-5 atoms. In light of recent data on the
possible isomerization of nitrocyclopropanes (13) to form Þve-membered cyclic
nitronates (5) (for more details, see Section 3.2.2.1.2), low chemoselectivity of
many reactions involving sulfur ylides does not seem to be so fatal.
When discussing the speciÞc features of various leaving groups in the synthesis
of nitronates presented in Scheme 3.12, the possibility of the use of the OH group
as the leaving group should be separately discussed. As in the synthesis of acyclic
nitronates, the Mitsunobu procedure (10) is apparently suitable for intramolecular
cyclization of acyclic γ-nitro alcohols (Scheme 3.17).
Unfortunately, only two attempts were made to use this approach in the
synthesis of Þve-membered cyclic nitronates (5), and only one of them could
be considered as successful. In the latter case, isomeric nitrocyclopropane was
obtained as the major product. Only α-functionalized nitro alcohols are readily
involved in the Mitsunobu cyclization. However, the possibility of isomerization
of by-products, nitrocyclopropanes, which was mentioned in the discussion of
Scheme 3.16, caused the revision of this process as a procedure for the synthesis
of Þve-membered cyclic nitronates. (A new approach to the synthesis of initial
γ-nitro alcohols from readily available AN was documented in Reference 64)
Recently, Italian researchers have developed a new procedure for the synthesis
of Þve-membered cyclic nitronates with the use of enantiomerically pure epoxides
(65–67) and aziridines (68) as the starting substrates (15) (Scheme 3.18, see also
substrate B in Scheme 3.11, Eq. 1).
A series of enantiomerically pure stereoisomeric nitronates (5a) and5a’ was
successfully prepared by varying the reaction conditions (the nature of the group
X, the catalyst, etc.) and using the solid-phase MerriÞeld synthesis (68).
In the synthesis of Þve-membered cyclic nitronates (5), the problem of stereoselectivity
is in preparing these products with desired relative conÞgurations of the
stereocenters at the C-4 and C-5 atoms (see Scheme 3.12). Generally, the trans
conÞguration of these substituents is most preferable. Several procedures giving
exclusively this conÞguration were documented (see,e.g. (50, 55, 58, 63, 68)).
R
O
+
R
NO 2