Synthesis of pyrrolidinones via free-radical cyclisations: potential application to the kainoids

Abstract

The tin hydride-mediated cyclisation of a range of DL-serine-derived α-chloro amides 1 to form pyrrolidinones has been examined. The yield and stereoselectivity of the cyclisation process was found to be markedly affected by the nature of the substituent at the site of radical generation. Thus, radicals substituted at the α-position by methyl, phenyl, dichloro and sulfanylphenyl substituents underwent smooth cyclisation to give excellent yields (58–95%) of a mixture of diastereoisomeric pyrrolidinones while the hydrogen-substituted congener cyclised in only 31–38% yield. This procedure has potential application to pyrrolidinone/pyrrolidine natural product synthesis and, in particular, to the kainoid amino acids.