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 language | English |
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Pages (from-to) | 4184-4209 |
Number of pages | 26 |
Journal | Journal of Organometallic Chemistry |
Volume | 689 |
Issue number | 24 SPEC. ISS. |
DOIs | |
Publication status | Published - 29 Nov 2004 |
Keywords
- Conjugate addition
- Enantiorecognition
- Iron acyl auxiliary