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

44 NITRILE OXIDES
Ph2CHCO N
H2C
N
Me Me
O 2CAr
Ph
Ph
Ph2CHCO N
O
N
N
Me Me
121 122
O2CAr Ph
The cycloaddition of nitrile oxides to 4-methylenetetrahydrothiopyran proceeds
regioselectively with the formation of spiro-substituted isoxazolines 123
(R = H, Cl, NO2). Semiempirical calculations (AM1) were used to analyze the
electronic structure of reactants, energies of products, and activation barriers
leading to these products, in order to rationalize this exclusive regioselectivity. It
was shown that the main factor responsible for the high stereoselectivity of this
reaction is not frontier orbital control, but mainly electrostatic and steric interactions.
Spiro compounds 123 were cleaved by hydrogenolysis to γ-amino alcohols
which were recyclized to spiro-oxazines (285). Cycloadditions of nitrile oxides
to 4-methylene-1-methylpiperidine gave spiro-substituted isoxazoline derivatives.
NMR studies conÞrmed that only one regioisomer was formed selectively. X-ray
structure analysis, carried out for one of these products, showed the occurrence
of only one stereoisomer, explicable by comparing AM1-calculated ΔHf values
of all possible cycloadducts (286).
S
123
Among heteroaromatic compounds able to react with nitrile oxides as dipolarophiles,
furan, probably, is the best known. Recently, a novel nitrile oxide was
generated from a sulfoximine and converted in situ to a cycloadduct with furan
(Scheme 1.25) (287). The starting racemic N-methyl-S-nitromethyl-S-phenylsulfoximine
124 was prepared in 87% yield via nitration of N,S-dimethyl-S-phenylsulfoximine.
Reaction of 124 with p-chlorophenyl isocyanate and a catalytic
quantity of triethylamine, in the presence of furan, afforded dihydrofuroisoxazole
125, the product of nitrile oxide cycloaddition, in 42% yield (65:35 diastereomer
ratio). The reaction of 125 with phenyllithium and methyllithium afforded compounds
126, which are products formed by replacement of the sulfoximine group
by Ph and Me, respectively.
Mesitonitrile oxide and acridine (1:2 ratio) react site- and regioselectively
to give mono-cycloadduct 127. The reaction of the same reagents in a 10:1
ratio afforded the mono-cycloadduct 127, and the bis-cycloadduct 128 with the
opposite regiochemistry to that of the mono-cycloadduct (288).
O
Ar
N
R
Ph