Synthesis of 2,4-, 3,4- and 2,3,4-substituted pyrrolidines by cyclization of neutral C-centered α-aminoalkyl radicals

The effect of substitution at C-3 or C-4 of the 2-azahex-5-enyl chain has been studied in the SmI2-promoted cyclizations of neutral α-aminoalkyl radicals generated from N-(α-benzotriazolyl)alkenylamines. 2,4-, 3,4- and 2,3,4-substituted pyrrolidines are obtained in this manner in uniformly high yields but with stereoselectivities which depend markedly on the substitution pattern. Thus, a methyl substituent at C-4 (hex-5-enyl numbering) effectively controls the stereochemistry over three contiguous stereogenic centers whereas substituents at C-3 are found to exert a very poor control. Stereochemical results are rationalized according to the existing models for radical ring-closures.