A Concise Cross-Metathesis Route to Enantiopure 1-Azaspirocycles

Authors Zhen James Wang, Nicolas Daniel Spiccia, Christopher James Gartshore, Jayamini Illesinghe, William Roy Jackson and Andrea Jane Robinson
Published Synthesis
Graphical abstract  



The 1-azaspirocyclic ring system can be found in a number of bioactive natural product families. Lepadiformine, cephalotaxine and cylindricine A all share a common spirocyclic pyrrolidine core, and fasicularin, halichlorine, histrionicotoxin and cylindricine B possess a homologous spirocyclic piperidine centre. This paper describes a concise synthesis of spiropyrrolidines and spiropiperidines which 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 stereo-retention.

Citation Z. J. Wang, N. D. Spiccia, C. J. Gartshore, J. Illesinghe, W. R. Jackson, A. J. Robinson, Synthesis, 2013, 45(22), 3118-3124.
Pdf Article
Doi DOI: 10.1055/s-0033-1338527
This entry was posted in Metathesis, Publications, Publications 2013 and tagged , . Bookmark the permalink.

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