Stereoselective conjugate addition reactions of lithium amides to α,β-unsaturated chiral iron acyl complexes [(η 5-C 5H 5)Fe(CO)(PPh 3)(COCH [dbnd]CHR)

Abstract

Conjugate addition of achiral lithium dimethylamide to the chiral iron cinnamoyl complexes ( S, E)- and ( S, Z)-[(η 5-C 5H 5)Fe(CO)(PPh 3)(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 α,β-unsaturated iron acyl complexes, followed by in-situ elaboration of the derived enolate by either alkylation or aldol reactions is also demonstrated, facilitating the stereoselective synthesis of both cis- and trans-β-lactams. This methodology has been used to effect the formal asymmetric syntheses of (±)-olivanic acid and (±)-thienamycin. Addition of chiral lithium amides derived from primary and secondary amines to the iron crotonyl complex [(η 5-C 5H 5)Fe(CO)(PPh 3)(COCH CHMe)] indicates that lithium N-α-methylbenzylamide shows low levels of enantiorecognition, while lithium N-3,4-dimethoxybenzyl- N-α-methylbenzylamide and lithium N-benzyl- N-α-methylbenzylamide show high levels of enantiodiscrimination. The high level of observed enantiorecognition was used to facilitate a kinetic resolution of ( RS)-[(η 5-C 5H 5)Fe(CO)(PPh 3)(COCH CHMe)] with homochiral lithium ( R)- N-3,4-dimethoxybenzyl- N-α-methylbenzylamide. Further mechanistic studies show that conjugate additions of ( RS)-lithium N-benzyl- N-α-methylbenzylamide to either the ( RS)- or homochiral iron crotonyl complex show 2:1 stoicheiometry, while homochiral lithium N-benzyl- N-α-methylbenzylamide shows 1:1 stoicheiometry.