Nickel-Catalyzed C-3 Direct Arylation of Pyridinium Ions for the Synthesis of 1-Azafluorenes

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2017 Jan 24

PMID 28111599

Citations 5

Authors

Jean-Nicolas Desrosiers

Xudong Wei

Osvaldo Gutierrez

Jolaine Savoie

Bo Qu

Xingzhong Zeng

Heewon Lee

Nelu Grinberg

Nizar Haddad

Nathan K Yee

Frank Roschangar

Jinhua J Song

Marisa C Kozlowski

Chris H Senanayake

Affiliations

Soon will be listed here.

Abstract

The direct arylation of pyridine substrates using non-precious catalysts is underdeveloped but highly desirable due to its efficiency to access important motifs while being extremely cost-effective. The first nickel-catalyzed C-3 direct arylation of pyridine derivatives to provide a new approach to valuable 1-azafluorene pharmacophore frameworks was developed. This transformation is accomplished using air-stable nickel catalyst precursors combined with phenanthroline ligands and tolerates a variety of substituents. Computational studies suggest facile oxidative addition via the pyridinium form, deprotonation, and a subsequent carbo-nickelation cyclization. Nickel homolysis/recombination permits isomerization to the stereochemical array needed for the final elimination.

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