Ligand-Enabled meta-Selective C-H Arylation of Nosyl-Protected Phenethylamines, Benzylamines, and 2-Aryl Anilines

J Am Chem Soc. 2017 Jan 11;139(1):417-425. doi: 10.1021/jacs.6b11097. Epub 2016 Dec 23.

Abstract

A Pd-catalyzed, meta-selective C-H arylation of nosyl-protected phenethylamines and benzylamines is disclosed using a combination of norbornene and pyridine-based ligands. Subjecting nosyl protected 2-aryl anilines to this protocol led to meta-C-H arylation at the remote aryl ring. A diverse range of aryl iodides are tolerated in this reaction, along with select heteroaryl iodides. Select aryl bromides bearing ortho-coordinating groups can also be utilized as effective coupling partners in this reaction. The use of pyridine ligands has allowed the palladium loading to be reduced to 2.5 mol %. Furthermore, a catalytic amount of 2-norbornene (20 mol %) to mediate this meta-C-H activation process is demonstrated for the first time. Utilization of a common protecting group as the directing group for meta-C-H activation of amines is an important feature of this reaction in terms of practical applications.

Publication types

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

MeSH terms

  • Aniline Compounds / chemistry*
  • Benzylamines / chemistry*
  • Ligands
  • Molecular Structure
  • Phenethylamines / chemistry*

Substances

  • Aniline Compounds
  • Benzylamines
  • Ligands
  • Phenethylamines