Applications of Intramolecular Amidomercuration. 2. Synthesis of trans-5-Hydroxy-2-propylpiperidine, (+/-)-Pseudoconhydrine

Article abstract of DOI:10.1021/jo00175a008

A method for the stereoselective conversion of δ-alkenyl carbamates into trans-2-alkyl-5-substitutes-piperidines utilizing intramolecular amidomercuration as key step has been developed.As a specific illustration of the method, a synthesis of one of the Hemlock alkaloids, (+/-)-Pseudoconhydrine (trans-5-hydroxy-2-propylpiperidine, 1) was completed.The organomercurial 7a obtained from the intramolecular amidomercuration of 4-<(carbobenzyloxy)amino>-7-octene (6) was converted to the corresponding trans-5-(iodomethyl)-2-propylpyrrolidine derivative 7b.Cleavage of the carbamate and treatment with base generated the bicyclic aziridine 2-exo-propyl-1-azabicyclo<3.1.0>hexane (8a).Treatment of this aziridine with excess trifluoroacetic acid gave ring opening to the disubstituted pyrrolidine derivative 9a exclusively.Ring opening of the analogous aziridine 8b with HCl gave mixtures of pyrrolidine 9b and piperidine 10b.However, these derivatives can be equilibrated through the neutral amine to a mixture consisting of ca. 85percent of the piperidine derivate.Slow addition of trifluoroacetic acid to the aziridine 8a allowed for equilibration to the piperidine 14 as the major product.Hydrolysis and purification gave pure racemic pseudoconhydrine.This sequence illustrates a synthetic equivalent to anti-Markovnikov cyclofunctionalization of δ-alkenyl carbamates.In addition, this study provided new information on the regiochemistry of ring opening bicyclic aziridines.