A modular and divergent approach to spirocyclic pyrrolidines |
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Authors: | Benjamin D. A. Shennan Peter W. Smith Yusuke Ogura Darren J. Dixon |
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Affiliation: | Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford UK, |
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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.A three-step, modular and divergent sequence accessing challenging spirocyclic pyrrolidines has been developed, featuring a novel reductive spirocyclization cascade. |
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