A modular and divergent approach to spirocyclic pyrrolidines
Benjamin D A Shennan1, Peter W Smith1, Yusuke Ogura1
1Department of Chemistry, Chemistry Research Laboratory, University of Oxford 12 Mansfield Road Oxford UK darren.dixon@chem.ox.ac.uk.
Abstract:
An efficient three-step sequence to afford a valuable class of spirocyclic pyrrolidines is reported. A reductive cleavage/Horner-Wadsworth-Emmons cascade facilitates the spirocyclisation of a range of isoxazolines bearing a distal β-ketophosphonate. The spirocyclisation precursors are elaborated in a facile and modular fashion, via a [3 + 2]-cycloaddition followed by the condensation of a phosphonate ester, introducing multiple points of divergence. The synthetic utility of this protocol has been demonstrated in the synthesis of a broad family of 1-azaspiro[4,4]nonanes and in a concise formal synthesis of the natural product (±)-cephalotaxine.
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