The Chemistry of Azocines. Intermediates for the Synthesis of Pyrrolizidines

Abstract

Investigations concerned with the preparation of 1,8-dihydro-and 1,6,7,8-tetrahydroazocines and the utilization of transannular reactions of Δ4,5-epoxyhexahydroazocmes for the generation of highly functionalized pyrrolizidines are described. Methods to synthesize 3,4-dicarbomethoxy-1,8-dihydro- and 1,6,7,8-tetrahydroazocines, 19 and 21, starting with 1,2-dihydropyridines, 22 and 16, having the N-α-styryl and N-bromomethyldioxolylethyl substituents as nitrogen protecting groups, are discussed and compared to unsuccessful attempts using a variety of common nitrogen blocking groups. In addition, procedures to convert azocines to functionalized pyrrolizidines using transannular cyclization reactions have been explored. A high yielding sequence starting with the Δ4,5-epoxyhexahydroazocine 33 and proceeding through the intermediate bicyclic amino ether 34 has been developed. The synthetic and mechanistic details of the chemistry regarding the preparation and reactions of azocines are discussed. © 1977, American Chemical Society. All rights reserved.