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

40 NITRILE OXIDES
H
O
N
H
O O
R
101 (R = 3,5-Cl2C6Me3)
Cycloaddition reactions of nitrile oxides with 5-unsubstituted 1,4-dihydropyridine
derivatives produced isoxazolo[5,4-b]pyridines in moderate to good
yield. In each case examined, the reaction produced only a single isomer, the
structure of which was assigned by NMR spectra and conÞrmed by X-ray diffraction
analysis of 102 (270). A study of the cycloaddition behavior of substituted
pyridazin-3-ones with aromatic nitrile oxides was carried out (271). Nitrile oxides
undergo position and regioselective 1,3-dipolar cycloaddition to the 4,5-double
bond of pyridazinone to afford 3a,7a-dihydroisoxazolo[4,5-d]pyridazin-4-ones,
for example, 103.
EtO 2C
N
O
H
N
Me H
102
H
CF 3
CO 2Et
Me
Me
O
N
Me
103
Ph
O Me
N
NMe
Reactions of benzonitrile oxide and its 4-substituted derivatives with
1-benzoyl-2-cyanodihydroquinoline gave mixtures of regioisomers 104 and 105
(R 1 = Bz, R 2 = CN). In contrast, the reaction with dihydroquinoline, bearing the
phenyl substituent in the position 2 and the benzyl group in the position 1,
gave only one regioisomer 105 (R 1 = PhCH2, R 2 = Ph) (272). The 1,3-dipolar
cycloaddition of aromatic nitrile oxides (generated in situ from aromatic aldoxime
precursors in a two-phase CHCl3/NaOCl system) to 1,2-dihydroisoquinoline
derivatives proceeds regioselectively and results in 3-aryl-3a,8,9,9a-tetrahydroisoxazolo[5,4-c]isoquinolines
(273). The latter undergo ring cleavage, under the
action of silica gel or reßuxing in ethanol in the presence of an acid, to give aryl
1,2-dihydro-4-isoquinolyl ketone oximes.
There are a few communications concerning cycloadditions of nitrile oxides
to unsaturated oxa and aza cage systems. Benzo- and mesitonitrile oxides RCNO
give, with Þve substituted 7-oxanorbornenes 106, mixtures of the corresponding
exo-adducts 107 and 108 in nearly quantitative yields. No traces of compounds
resulting from the endo-face attack was detected (274). Substituents at positions
5and6of106 render the process highly regioselective.