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=CHR)]

Stephen G. Davies, Jairton Dupont, Robert J.C. Easton, Osamu Ichihara, Jeffrey M. McKenna, Andrew D. Smith, José A.A. De Sousa

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Abstract

The conjugate additions of a range of achiral and homochiral lithium amides derived from primary and secondary amines to α,β-unsaturated chiral iron acyl complexes [(η 5-C 5H 5)Fe(CO) (PPh 3)(COCHCHR)] have been studied to determine the extent of enantiorecognition in these reactions, and for the asymmetric synthesis of β-amino acids and β-lactams. 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)(COCHCHPh)] 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)(COCHCHMe) ] 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)(COCHCHMe)] 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.

Original languageEnglish
Pages (from-to)4184-4209
Number of pages26
JournalJournal of Organometallic Chemistry
Volume689
Issue number24 SPEC. ISS.
DOIs
Publication statusPublished - 29 Nov 2004

Keywords

  • Conjugate addition
  • Enantiorecognition
  • Iron acyl auxiliary

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