A Concise Cross-Metathesis Route to Enantiopure 1-Azaspirocycles

We dedicate this manuscript to Adrian Blackman (University of Tasmania) and wish him well in his retirement.

Abstract

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.

Key words

spiro compounds - metathesis - ring expansion - catalysis - piperidines - pyrrolidines

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