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

Roberta Galeazzi, Giovanna Mobbili, Mario Orena

Research output: Contribution to journalArticlepeer-review

Abstract

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 · 2H2O 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 1H 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.

Original languageEnglish
Pages (from-to)1069-1084
Number of pages16
JournalTetrahedron
Volume52
Issue number3
DOIs
Publication statusPublished - Jan 15 1996

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

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