A chiral base desymmetrisation-ring- closing metathesis route to chiral azaspirocycles: Synthesis of core structures related to pinnaic acid and halichlorine

A range of highly functionalised chiral azaspirocycles was synthesised, starting from a piperidine diester that is available in 90% ee from a chiral base desymmetrisation. The approach depends upon the use of Grignard addition reactions or a Claisen rearrangement to provide intermediates capable of undergoing ring-closing metathesis. A number of intermediates related to the core structure of pinnaic acid were synthesised by concise routes using the approach.