Stereoselective electrophilic reactions using azaallyllithium reagents generated from acyclic imidate esters

Abstract

The generation and synthetic utility of azaallyllithium reagents from acyclic imidate esters was described. The acyclic imidate esters 5-15, 18-22, 31-33, 34, 36 and 37 were prepared by various methods. Azaallyllithium reagents were generated by deprotonation of these acyclic imidate esters using n-BuLi or LDEA. These azaallyllithium reagents were relatively stable in THF even above -23(DEGREES)C. They also reacted with a variety of alkyl halides to yield (alpha)-alkylated products in yields that ranged from 16-97%. From ('13)C NMR studies and correlation with similar species, it was determined that azaallyllithium reagents like 100 had the Z(,C=C), E(,C-N) configuration. Aldol condensations using azaallyllithium reagents generated from acyclic imidate esters were also performed. It was observed that (beta)-hydroxyimidate esters were produced in moderate yields with stereoselectivities that ranged from 1.1:1 to 11:1. The threo isomer was the major stereoisomer observed. These aldol condensations proceeded to give the thermodynamically favored product. Several asymmetric syntheses were performed using chiral azaallyllithium reagents generated from acyclic imidate esters 19, 22, 36 and 37. The diastereoselectivities (de's) observed in these reactions varied from 20-97% de. The best results were obtained with imidate ester 22 derived from (-)-((alpha))-phenylglycine. Hydrolysis of these imidate esters with 3 N H(,2)SO(,4) led to carboxylic acids which were considerably racemized.