Stereoselective conjugate addition reactions of lithium amides to α,β-unsaturated chiral iron acyl complexes [(η5-C5H5)Fe(CO)(PPh3)(COCH=CHR)]

Conjugate addition of achiral lithium dimethylamide to the chiral iron cinnamoyl complexes (S,E)- and (S,Z)-[(eta(5)-C5H5)Fe(CO)(PPh3)(COCH=CHPh)] proceeds with high diastereoselectivity, with this protocol being used to establish unambiguously the absolute configuration of Winterstein's acid (3-N,N-dimethylamino-3-phenylpropanoic acid) as (R). The highly diastereoselective conjugate addition of lithium N-benzyl-N-trimethylsilylamide to a range of alpha,beta-unsaturated iron acyl complexes, followed by insitu elaboration of the derived enolate by either alkylation or aldol reactions is also demonstrated, facilitating the stereoselective synthesis of both cis- and trans-beta-lactams. This methodology has been used to effect the formal asymmetric syntheses of (+/-)-olivarric acid and (+/-)-thienamycin. Addition of chiral lithium amides derived from primary and secondary amines to the iron crotonyl complex [(eta(5)-C5H5)Fe(CO)(PPh3)(COCH=CHMe)] indicates that lithium N-alpha-methylbenzylamide shows low levels of enantiorecognition, while lithium N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide and lithium N-benzyl-N-alpha-methylbenzylamide show high levels of enantiodiscrimination. The high level of observed enantiorecognition was used to facilitate a kinetic resolution of (RS)-[(eta(5)- C5H5)Fe(CO)(PPh3)(COCH=CHMe)] with homochiral lithium (R)-N-3,4-dimethoxybenzyl-N-a-methylbenzylamide. Further mechanistic studies show that conjugate additions of (RS)-lithium N-benzyl-N-alpha-methylbenzylamide to either the (RS)- or homochiral iron crotonyl complex show 2:1 stoicheiometry, while homochiral lithium N-benzyl-N-alpha-methylbenzylamide shows 1: 1 stoicheiometry. (C) 2004 Elsevier B.V. All rights reserved.