Second-Generation Palladium Catalyst System for Transannular C-H Functionalization of Azabicycloalkanes

J Am Chem Soc. 2018 Apr 25;140(16):5599-5606. doi: 10.1021/jacs.8b02142. Epub 2018 Apr 13.

Abstract

This article describes the development of a second-generation catalyst system for the transannular C-H functionalization of alicyclic amines. Pyridine- and quinoline-carboxylate ligands are shown to be highly effective for increasing the reaction rate, yield, and scope of Pd-catalyzed transannular C-H arylation reactions of azabicyclo[3.1.0]hexane, azabicyclo[3.1.1]heptane, azabicyclo[3.2.1]octane, and piperidine derivatives. Mechanistic studies reveal that the pyridine/quinoline-carboxylates play a role in impeding both reversible and irreversible catalyst decomposition pathways. These ligands enable the first reported examples of the transannular C-H arylation of the ubiquitous tropane, 7-azanorbornane, and homotropane cores. Finally, the pyridine/quinoline-carboxylates are shown to promote both transannular C-H arylation and transannular C-H dehydrogenation on a homotropane substrate.

Publication types

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

MeSH terms

  • Alkanes / chemistry*
  • Azabicyclo Compounds / chemistry*
  • Catalysis
  • Ligands
  • Palladium / chemistry*
  • Pyridines / chemistry
  • Quinolines / chemistry

Substances

  • Alkanes
  • Azabicyclo Compounds
  • Ligands
  • Pyridines
  • Quinolines
  • Palladium