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

20 NITRILE OXIDES
(136, 137), application of cyclodextrin-based catalysts and molecular reactors in
1,3-dipolar cycloaddition reactions of nitrile oxides (138, 139).
In the scope of this subsection, competitive 1,3-cycloaddition of nitrile oxides
to carbon–carbon and carbon–heteroatom multiple bonds are of special interest.
Competition between carbon–carbon and carbon–nitrogen double bonds in
1,3-cycloaddition reactions with benzonitrile oxides is the subject of a review
(140). 1,3-Dipolar cycloaddition reactions of o-benzoquinones are summarized in
Reference 141. Depending on the nature of the substrates and of the substituents,
benzonitrile oxides add to both C=C and C=X bonds.
Several papers concerning modern modiÞcations of 1,3-cycloaddition reactions
of nitrile oxides should be also mentioned. An efÞcient solution-phase combinatorial
synthesis of isoxazolines and isoxazoles, using [2 + 3] cycloaddition reaction
of nitrile oxides with oleÞns and alkynes, followed by precipitation of the products
as HCl salts has been developed (142). A general method for the liquid-phase
syntheses of isoxazoles and isoxazolines via a 1,3-dipolar cycloadditions is elaborated.
Poly(ethylene glycol)-supported alkyne or alkene react with nitrile oxides,
generated in situ from aldoximes followed by elimination from the poly(ethylene
glycol) support, to give target products in good yield and purity (143).
One-pot 1,3-dipolar cycloaddition of nitrile oxides generated in situ on solid
phase, in the presence of a variety of dipolarophiles, provided a library of isoxazolines
and isoxazoles (144). (4S )-p-Hydroxybenzyl-1,3-oxazolidin-2-one was
used as a solid-supported chiral auxiliary in asymmetric 1,3-dipolar cycloadditions
(145). It was also shown that Mg(II) cation (from magnesium perchlorate)
catalyzes asymmetric 1,3-dipolar cycloaddition reactions using solid-supported
oxazolidinone chiral auxiliaries (146). The results obtained support a reaction
mechanism, which proposes the coordination of the Mg(II) to the dicarbonyl
fragment of the chiral auxiliary. The resin-bound chiral auxiliaries could be recycled
once, with little loss in regio- or stereoselectivity, but a second recycle gave
products with signiÞcantly decreased regio- and stereoselectivities.
It was found that 2-propenyloxymagnesium bromide reacts much more readily
with nitrile oxides than other known dipolarophiles of electron-deÞcient,
electron-rich, and strained types, including 3-buten-2-one, ethyl vinyl ether, and
norbornene, respectively (147). Therefore, this BrMg-alkoxide is highly effective
in various nitrile oxide cycloaddition reactions, including those of nitrile
oxide/Lewis acid complexes.
An unusual solvent effect was observed in cycloadditions of aromatic nitrile
N-oxides with alkyl-substituted p-benzoquinones in ethanol-water (60:40): the
reaction rates were 14-fold greater than those in chloroform (148). The use of ion
pairs to control nitrile oxide cycloadditions was demonstrated. A chiral auxiliary
bearing an ionic group and an associated counterion provides enhanced selectivity
in the cycloaddition: the intramolecular salt effect controls the orientation of the
1,3-dipolar reagent (149).
Microwave irradiation promotes the 1,3-dipolar activity of nitrile oxides generated
from hydroximoyl chlorides. They interacted in situ over alumina with
alkenes and alkynes (150). The effect was demonstrated in reactions of