(3,4-Dimethoxyphenyl)acetic acid (93-40-3) 's Synthetic route

A modular and divergent approach to spirocyclic pyrrolidines

Dixon, Darren J.  Ogura, Yusuke  Shennan, Benjamin D. A.  Smith, Peter W.

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,viaa [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.