Role of remote heteroatoms and nature of the reducing agents on the stereochemical course of reductions of the carbon–nitrogen π-bond of a new class of tetrahydropyridines

Abstract

Total syntheses of the tetrahydropyridine derivatives (3a–f) and the steroid analogue (1b) are reported. Catalytic reductions of the above imines have been found to be highly stereoselective, yielding only the trans-amine in most cases. Lithium aluminium hydride reductions of the above imines (3a–e), (1b), and (3f–g), however, showed cis-stereoselectivity; the imines (3a–b) and (1b) afforded only the cis-amines under these conditions. Sodium borohydride reductions of the imines (3a–g) gave conflicting results, the imines (3a–b) and (3f–g) furnishing stereoselectively the trans-amines. Metal–ammonia reductions of the imines (3a–b) and (3f), having a carbocyclic B ring, gave a stereoisomeric mixture of amines; similar reduction of the imines (3c–d) with an oxygen atom in ring B, provided, interestingly, the corresponding trans-amines as the predominant product (84–94%). Reasons for the different stereochemical results observed in the reductions of the imines (3a–g) with various reducing agents have been briefly discussed. The stereochemical assignments of the amines (14)–(15) and (16)–(17) were secured from their ¹H and ¹³C n.m.r. spectra, and also from ¹H n.m.r. spectra of their N-acetyl derivatives.