Synthesis of (+)‐ and (−)‐hydroxysedamine and (+)‐<i>N</i>‐methylpseudoconhydrine from (<i>S</i>)‐glutamic acid via homochiral acyliminium ion

Abstract

Abstract Efficient syntheses of (+)‐ N ‐methylpseudoconhydrine ( 5 ) and (−)‐hydroxysedamine ( 10 ) are described starting from the readily available (2 RS,5S )‐Methyl 5‐( tert ‐butyldimethyl‐silyloxy)‐2‐ethoxypiperidine‐1‐carboxylate ( 1 ) and proceeding via homochiral acyliminium ion as an intermediate. Compounds 5 and 7b were obtained in 32 and 34%, resp., overall yield from 1. After deprotection of the OH function of 3a, b the diastereomeric mixture of 6a, b was separated and converted to pseudoconhydrine 7b and epi‐pseudoconhydrine 7a , respectively. Reduction of the urethane moiety of 3a, b followed by treatment with hydrochloric acid provided enantio‐ and diastereopure 5. Reaction of 1‐phenyl‐1‐(trimethylsiloxy)ethene with 1 afforded 8a and 8b in a ratio of 1:9. Deprotection of 8a, b and separation of the diastereomers give after diastereoselective reduction of the ketone function and conversion of the urethane moiety into the methyl group natural (−)‐hydroxysedamine ( 10 ). Starting from 8b , deprotection and inversion of the OH function furnished 12 as a single homochiral diastereomer which was converted to ent‐10 .