A convenient approach to diastereomerically pure 1,3,4-trisubstituted pyrrolidin-2-ones by intramolecular cyclisation of N-(2-alken-1-yl)amides mediated by Mn(III). An entry to both (R)- and (S)-3-pyrrolidineacetic acid

The oxidative cyclisation of a series of either (S),-N-(2-alken-1-yl)-N-(1-phenyleth-1-yl)-acetoacetamides 5a-d and methoxycarbonylacetamides 6a-b, performed by using Mn(OAc)(3) . 2H(2)O and Cu(OAc)(2) . H2O in acetic acid, has been examined. The reaction proceeds regioselectively through a 5-exo-mode, leading to 1,3,4-trisubstituted pyrrolidin-2-ones 7a-d,8a-d and 9a-b,10a-b as diastereomeric mixtures in about 2:1 ratio? which are easily separated by silica gel chromatography. The configuration of the pure diastereomers is assigned from H-1 NMR data and confirmed by NOE experiments. The observed asymmetric induction has been explained on the basis of molecular mechanics calculations. This cyclisation constitutes a useful tool for the synthesis of biologically active amino acids containing the pyrrolidine ring in both enantiomerically pure forms, such as (R)-and(S)-3-pyrrolidineacetic acid, 1 and 2.