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A modular and divergent approach to spirocyclic pyrrolidines.

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.

SUBMITTER: Shennan BDA

PROVIDER: S-EPMC8162384 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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A modular and divergent approach to spirocyclic pyrrolidines.

Shennan Benjamin D A BDA Smith Peter W PW Ogura Yusuke Y Dixon Darren J DJ

Chemical science 20200807 38

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, <i>via</i> a [3 + 2]-cycloaddition followed by the condensation of a phosphonate ester, introducing multiple points of divergence. The synthetic utility of this protocol ...[more]

PMID: 34094297

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