Stereoselective synthesis of fused γ-lactams by intramolecular nitrone cycloaddition

Abstract

A series of nitrones 5 joined by amides to olefines were prepared in situ from the related aldehydes with N-methylhydroxylamine. The nitrones added intramolecularly to the olefin, and the cycloadditions gave fused γ-lactams 6 stereoselectively. A stereocentre located in position α to the nitronic functionality 13 completely controls the stereochemical course of the intramolecular cycloadditions, which exclusively affords compound 14 with simultaneous introduction of four stereocentres. The formation of this latter compound was also supported by PM3 calculations. Furthermore, simple heating of unsaturated oxime 17 led to compound 19 via intramolecular oxime olefin cycloaddition.