Synthesis and reactions of 1‐[1‐oxido‐2‐(3,4)‐pyridinyl]‐2‐methyloxiranes with nitrogen nucleophiles

Abstract

Reaction of 2(3,4)‐pyridinecarboxaldehydes (5) with ethylidenetriphenylphosphorane afford a mixture of stereoisomers Z‐(6) and E‐1‐[2(3,4)‐pyridinyl]‐1‐propenes (7). m‐Chloroperbenzoic acid oxidation of 6 and 7 yields a 60:40 mixture of Z‐(8) and E‐1‐[1‐oxido‐2(3,4)‐pyridinyl]‐2‐methyloxiranes (9). The regiospecific reaction of Z‐isomers 8a‐c with cyclic amines as piperidine give rise to threo‐1‐hydroxy‐1‐[1‐oxido‐2(3,4)‐pyridinyl]‐2‐(1‐piperidino)propanes (10) while the E‐isomer 9a yields erythro‐11. On tho other hand, the E‐isomers 9b and 9c having 1‐oxido‐3(4)‐pyridinyl substituents afford erythro‐12 resulting from attack by piperidine at C‐1 of the oxirane. Reductive deoxygenation using 10% palladium on charcoal and hydrogen gas effectively removed the N‐oxide substituent from the threo‐10 and erythro‐11 β‐aminoalcohols. Dilute solution ir spectroscopy indicated the existance of strong intramolecular hydrogen bonding in the β‐aminoalcohols 10 and 11. The assignment of relative configuration of diastereoisomers 10 and 11 was based on the magnitude of the vicinal coupling constant J where J threo is greater than J erythro.