A diastereoselective radical cyclization approach to substituted quinuclidines

J Org Chem. 2006 Apr 28;71(9):3656-9. doi: 10.1021/jo060349q.

Abstract

A new, concise, and flexible approach to novel quinuclidines has been developed, which employs a phosphorus hydride mediated radical addition/cyclization reaction in the key step. 1,7-Diene 5 reacts with diethyl thiophosphite in an efficient and diastereoselective radical addition/cyclization reaction to give trisubstituted piperidines 4ab. Piperidines 4ab are subsequently converted into 2,5-disubstituted quinuclidines using S(N)2-type cyclizations. Finally, the resulting quinuclidines are shown to undergo novel Horner-Wadsworth-Emmons-type (HWE-type) reactions to give unsaturated quinuclidines 21a and 21b, which have structures similar to that of (-)-quinine 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • Free Radicals / chemistry
  • Quinuclidines / chemical synthesis*
  • Quinuclidines / chemistry
  • Stereoisomerism

Substances

  • Free Radicals
  • Quinuclidines