Efficient tin hydride-mediated radical cyclisation of secondary amides. Part 1. Synthesis of a variety of substituted pyrrolidinones

The tin hydride-mediated 5-exo-trig cyclisation of a variety of secondary h aloamides under mild, neutral reaction conditions has been investigated. Cy clisation was found to produce substituted pyrrolidinones in good to reason able yield when the reaction was carried out in boiling toluene; lower yiel ds were observed when using boiling benzene. The predominant formation of t he trans-(C-3-C-4) isomers is consistent with a reversible cyclisation lead ing to the thermodynamically more stable product. The nature of the accepto r carbon-carbon double bond and substituents at the radical centre were fou nd to influence the stereoselectivity of the cyclisation: more of the cis-i somer was isolated from precursors bearing a radical stabilising group on t he alkene. This can be explained by a slower radical ring opening (or fragm entation) reaction leading to more of the kinetic (cis) product. The introd uction of substituents alpha to nitrogen (which can influence the amide con former population) improved the yield of cyclisation and substituted pyrrol idinones could be isolated in up to 76% yield.