Conjugate addition reactions of N-carbamoyl-4-pyridones and 2,3-dihydropyridones with Grignard reagents in the absence of Cu(I) salts

J Org Chem. 2013 Sep 6;78(17):8451-64. doi: 10.1021/jo400936z. Epub 2013 Aug 13.


N-Boc- and N-ethoxycarbonyl-4-pyridones and the resulting 2,3-dihydropyridones undergo 1,4-addition reactions with Grignard reagents in the presence of chlorotrimethylsilane (TMSCl) or BF3·Et2O in excellent yields. Copper catalysis is not required, and mechanistic considerations suggest that the reaction is proceeding by a conjugate addition pathway rather than by a pathway involving 1,2-addition to an intermediate pyridinium ion. TMSCl-mediated conjugate addition of Grignard reagents to 2-substituted-2,3-dihydropyridones gives the trans-2,6-disubstitued piperidinones stereoselectively, while cuprate reagents give either the trans or cis diastereomers or mixtures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Pyridones / chemistry*


  • Organometallic Compounds
  • Piperidines
  • Pyridones