Stereoselective Synthesis of 2,4,5-Trisubstituted Piperidines via Radical Cyclization

Research output: Contribution to journalArticle


  • ME Ragoussi
  • SM Walker
  • A Piccanello
  • BM Kariuki
  • PN Horton
  • Neil Spencer

Colleges, School and Institutes


A novel approach to 2,4,5-trisubstituted piperidines is reported, involving the 6-exo cyclization of stabilized radicals onto alpha,beta-unsaturated esters. Only two of the four possible diastereoisomers are observed, with diastereomeric ratios ranging from 3:2 to 40:1 when the radical stabilizing group is vinyl or phenyl. Cyclization of a (triethylsilyl)vinyl-stabilized radical gives the corresponding piperidine radical as a single diastereoisomer that may either be trapped by tributyltin hydride to afford the 2,4,5-trisubstituted piperidine or undergo a second 5-endo cyclization onto the (triethylsilyl)vinyl substituent to produce the 3,5,7-trisubstituted octahydro[2]pyrindene as a single diastereoisomer.


Original languageEnglish
Pages (from-to)7347-7357
Number of pages11
JournalThe Journal of Organic Chemistry
Issue number21
Publication statusPublished - 1 Nov 2010