Stereoselective Synthesis of Highly Substituted γ-Lactams

Abstract

The [3+2] annulation reaction of α-siloxy allylsilanes 1 with N-chlorosulfonyl isocyanate provides an efficient stereoselective synthesis of γ-lactams. After reductive removal of the chlorosulfonyl moiety, the only annulation product formed was the γ-lactam 2 as a single diastereo­mer. In all cases, γ-lactams were formed exclusively, without formation of the N-chlorosulfonyl iminolactone. This [3+2] annulation was general for a wide range of α-siloxy allylsilanes. No loss of optical purity occurred when enantioenriched allylsilanes were used, affording nonracemic γ-lactams. Compounds bearing tetrasubstituted carbon stereocenters and useful bicyclic structures were accessed. The reaction was demonstrated to be stereospecific. Electron-donating and hindered silyl groups were found to increase the yields. The resulting γ-lactams can be further substituted at the α-position by diastereoselective nucleophilic substitution via an N-acyliminium ion to provide γ-lactams 3. Oxidative cleavage of the C-Si bond provided highly substituted β-hydroxy-γ-lactams as single diastereomers.