A Concise Cross-Metathesis Route to Enantiopure 1-Azaspirocycles

A concise synthesis of spiropyrrolidines and spiropiperidines has been developed. The approach employs a ruthenium-alkylidene-catalysed cross-metathesis reaction of enantiopure N-protected allylglycine with methylenecycloalkanes. The resultant alkene intermediates can then undergo a tandem acid-catalysed cyclisation to form spiropyrrolidines. Ring expansion of the spiropyrrolidine system, via an aziridinium intermediate, grants access to the homologous spiropiperidine ring system with excellent stereoretention.