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

446 NITRONATES
p-NO 2-C 6H 4
NO2
Br CN
NO2
MeONa/MeOH
Et 2O
Scheme 3.13
p-NO2-C6H4
CN
O N
NO2 O
In some cases, Þve-membered cyclic nitronates can be prepared by the chemoselective
replacement of one of two different halogen atoms in 1,3-dihalopropanes
(6) by the nitro group followed by intramolecular O-alkylation of the resulting
intermediates (Scheme 3.14, Eq. 1).
Another approach is based on the Henry condensation of activated primary AN
(7) with aldehydes followed by dehydration and addition of the second molecule
(7) to the resulting Michael substrate (Scheme 3.14, Eq. 2). This process is
particularly convenient for the synthesis of Þve-membered cyclic nitronates (5)
containing identical functional groups at the C-3 and C-5 atoms.
The third strategy for the synthesis of (5) involves the Michael addition of primary
AN (8) to conjugated α-halo-enones followed by cyclization of the resulting
intermediates (Scheme 3.14, Eq. 3).
Yet another approach to the synthesis of Þve-membered cyclic nitronates (5)
is based on the Henry condensation of α-halo-substituted aldehydes (9) with
primary AN followed by cyclization of nitroaldols (Scheme 3.14, Eq. 4) to give
Þve-membered nitronates containing the hydroxy group at the C-4 atom.
Finally, Scheme 3.14 presents the Michael addition of bromomalonic ester
to conjugated nitro oleÞns 10. This approach allows one to synthesize Þvemembered
cyclic nitronates (5) doubly functionalized at the C-5 atom (Scheme
3.14, Eq. 5).
In the synthesis of nitronates (5), longer reaction sequences can also be
successfully used. For example, Scheme 3.15 presents the synthesis of trisubstituted
nitronates (5) from functionalized primary AN (11) (exempliÞed by methyl
nitroacetate) and alkyl iodides RCH2I (56).
The reaction requires an excess of (11) and proceeds through intermediate
acyclic alkyl nitronates A. Thermal decomposition of the latter affords aldehydes
RCHO, whose condensation with the starting nitro compounds (11) (cf. Eq. 2 in
Scheme 3.14) gives target cyclic nitronates (5) in 35% to 45% yield. In spite of
the fact that the starting compounds 11 are readily available, the evident drawback
of this strategy (the use of a large excess of AN 11) seems to be not as strong.
In all the above examples, the synthesis of nitronates (5) is rather chemoselective.
In any case, data on the formation of their structural isomers, viz, the
corresponding nitrocyclopropanes (13), are lacking. However, the synthesis of
Þve-membered nitronates (5) with the use of sulfur or selenium ylides is not
chemoselective (see Scheme 3.16).
Nitronates (5) can be synthesized by the Michael addition of in situ generated
sulfur or selenium ylides (12) (58–60, 62, 63) to conjugated nitroalkenes