Synthesis of Highly Substituted and Enantiomerically Pure 2,3,4-Tris(hydroxyalkyl)pyrrolidines Using a 1,3-Dipolar Cycloaddition Reaction as Key Step

Abstract

The major endo cycloadducts with a basic structure of methyl 1-aryl-3-(benzyl or methyl)-6-menthyloxy-7-oxooctahydropyrano[4,3-c]pyrrole-3-carboxylate were subjected to simple chemical transformations (mostly reduction and hydrolysis reactions) to afford pyrrolidine bicyclic systems with varied patterns of substitution and configurations. The cycloadducts have been obtained by the 1,3-dipolar cycloaddition of (S)-2-menthyloxy-2H-pyran-3(6H)-one, derived from D-xylose, with azomethine ylides derived from imines of L-alanine or L-phenylalanine. The synthetic route led to enantiomerically pure 2,3,4-tris(hydroxyalkyl) pyrrolidines possessing a tetrasubstituted carbon stereocenter vicinal to the ring nitrogen atom and carrying a phenyl substituent on the other carbon adjacent to the nitrogen.