Direct Formation of 2-Substituted 2 H-Indazoles by a Pd-Catalyzed Reaction between 2-Halobenzyl Halides and Arylhydrazines

Nayyef Aljaar; Mousa Al-Noaimi; Jürgen Conrad; Uwe Beifuss

doi:10.1021/acs.joc.0c01923

Direct Formation of 2-Substituted 2 H-Indazoles by a Pd-Catalyzed Reaction between 2-Halobenzyl Halides and Arylhydrazines

J Org Chem. 2021 Jan 15;86(2):1408-1418. doi: 10.1021/acs.joc.0c01923. Epub 2020 Dec 11.

Authors

Nayyef Aljaar¹, Mousa Al-Noaimi¹, Jürgen Conrad², Uwe Beifuss²

Affiliations

¹ Department of Chemistry, Faculty of Science, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan.
² Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstraße 30, Stuttgart D-70599, Germany.

PMID: 33306383
DOI: 10.1021/acs.joc.0c01923

Abstract

A direct and operationally simple method for the regioselective synthesis of 2-aryl-substituted 2H-indazoles is reported. The Pd-catalyzed reaction between easily available 2-bromobenzyl bromides and arylhydrazines employing Cs₂CO₃ as the base and t-Bu₃PHBF₄ as the ligand in DMSO at 120 °C in a sealed tube delivers the 2-substituted-2H-indazoles in a single synthetic step with yields up to 79%. The new method is based on a regioselective intermolecular N-benzylation followed by intramolecular N-arylation and oxidation.

Publication types

Research Support, Non-U.S. Gov't