Synthesis of Spirocyclopropyl γ-Lactams by a Highly Stereoselective Tandem Intramolecular Azetidine Ring-Opening/Closing Cascade Reaction

A new tandem intramolecular azetidine ring-opening/closing cascade reaction affording spirocyclopropyl γ-lactams in high regio- and stereoselectivity is reported. The key step of the process is an S N 2-type ring-opening of TMSOTf-activated azetidine rings by silyl ketene acetals generated by treatment with TMSOTf and triethylamine. This study is a very rare example of nucleophilic ring opening of azetidines that does not require formation of quaternary azetidinium salts by N-alkylation or the use of N-electron-withdrawing groups.