Pd-catalyzed regioselective arylation on the C-5 position of N-aryl 1,2,3-triazoles

J Org Chem. 2015 Mar 20;80(6):3003-11. doi: 10.1021/jo5026145. Epub 2015 Mar 4.

Abstract

We herein report a highly efficient method for the arylation at the C-5 position of N-aryl 1,2,3-triazoles via a direct palladium catalyzed arylation reaction. The optimal reaction conditions required a combination of Pd(OAc)2 and tris(o-tolyl)phosphine as catalyst, and Cs2CO3 as the base under inert atmosphere. A variety of C-5 substituted N-aryl 1,2,3-triazoles were prepared using these conditions with yields in the 70-88% range. Regioselective C-5 arylations were also performed on 1,4-disubstituted 1,2,3-triazoles. The regioselectivity in triazole substitution at the C-5 position was confirmed by single crystal XRD. In addition, computational investigations of key steps of the catalytic cycle using the density functional theory have provided a rationalization to the selective C-5 arylation of N-aryl 1,2,3-triazoles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • Palladium / chemistry*
  • Quantum Theory
  • Stereoisomerism
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry

Substances

  • Organometallic Compounds
  • Triazoles
  • Palladium