N-Heterocyclic Carbene Ligand-Enabled C(sp(3))-H Arylation of Piperidine and Tetrahydropyran Derivatives

Chemistry. 2016 Mar 24;22(14):4748-52. doi: 10.1002/chem.201600191. Epub 2016 Feb 24.

Abstract

Pd(II)-catalyzed C(sp(3))-H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N-heterocyclic carbene (NHC) ligand. A C(sp(3))-H insertion step by the Pd(II)/NHC complex in the absence of ArI is demonstrated experimentally for the first time. Experimental data suggests that the previously established NHC-mediated Pd(0)/Pd(II) catalytic manifold does not operate in this reaction. This transformation provides a new approach for diversifying pharmaceutically relevant piperidine and tetrahydropyran ring systems.

Keywords: C−H activation; N-heterocyclic carbenes; arylation; heterocycles; palladium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Ligands
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Molecular Structure
  • Piperidines / chemistry*
  • Pyrans / chemistry*

Substances

  • Ligands
  • Piperidines
  • Pyrans
  • carbene
  • Methane