Asymmetric synthesis via the iron chiral auxiliary [(n5-C5H5)Fe(CO)(PPh3)]

Abstract

The acetyl ligand attached to the iron chiral auxiliary [(n5-C5H5)Fe(C0)(PPh3)] can be elaborated with a high degree of stereochemical control to yield, after decomplexation, (-)-captopril and β-lactams essentially optically pure. Methylation of the (R)-acetyl complex 1, via its enolate, gave the (R)-propanoyl complex 7. Treatment of 7 with butyllithium to generate the E-enolate and trapping with bromomethyl benzylthioether gave (RS)-8 as a single compound. Oxidative decomplexation of (RS)-8 in the presence of the benzyl ester of 1-proline followed by deprotection gave (-)-captopril 6. Sequential O-methylation and base induced elimination of β-hydroxyacyl complexes derived by trapping the enolate from 1 with aldehydes generates stereoselectively E-α,β-unsaturated acyl complexes. These E-α,β-unsaturated acyl complexes undergo stereoselective tandem Michael addition reactions and alkylations to give single diastereoisomers of products indicating complete control over both new chiral centres. This methodology has been applied to the asymmetric synthesis of (2R,3H)-(-)-N-benzyl-2,3-dimethylheptanamide 20, (3R,4S)-(-)-cis-3,4-dimethyl-N-benzyl-β-lactam 22 and (4S)-(-)-4-methyl-25 N-benzyl-β-lactam via the (S)-E-crotonyl complex 23 derived from the (S)-acetyl complex 1. © 1988 IUPAC