Use of highly stereospecific 1,3-dipolar cycloadditions of cyclic nitrones with acetylenes in the preparation of novel heterocyclic ring systems

Abstract

Cyclic nitrones with substituents α to the nitrogen atom undergo 1,3-dipolar cycloadditions in a stereo- and regio-specific manner with acetylenes. The nitrone 3 reacts with methyl propiolate, methyl phenylpropiolate and methyl acetylpropiolate to give the corresponding pyrrolo[1,2-b]isoxazoles 5, 8 and 13 respectively. Compound 13 reacts with 4-chlorophenylhydrazine to afford the pyrazolo[4,3-a]pyrrolizine 15 by a novel rearrangement. The nitrone 18 undergoes a 1,3-dipolar cycloaddition with methyl propiolate in a stereo- and regio-specific manner to give the isoxazolo[2,3-a]pyridine 19. The nitrone 18, when reacted with methyl acetylpropiolate, gives a mixture of regioisomers in a ratio of 3∶2. The major regioisomer 21 reacts with 4-chlorophenylhydrazine to afford the novel pyrazolo[4,3-a]indolizine ring system 23. The bicyclic nitrone 26 reacts with methyl propiolate and methyl acetylpropiolate to give the cycloadducts 27 and 28 respectively; both these compounds contain the novel isoxazolo[3,2-i]indole ring system.