title: Nickel-Catalyzed C-3 Direct Arylation of Pyridinium Ions for the Synthesis of 1-Azafluorenes.
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.
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Desrosiers
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Gutierrez
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Jolaine
authors.initials: J
authors.lastname: Savoie
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Qu
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Xingzhong
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Heewon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Nelu
authors.initials: N
authors.lastname: Grinberg
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Nizar
authors.initials: N
authors.lastname: Haddad
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Yee
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Roschangar
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Jinhua J
authors.initials: JJ
authors.lastname: Song
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
authors.forename: Marisa C
authors.initials: MC
authors.lastname: Kozlowski
authors.affiliation: Department of Chemical Development US, Boehringer-Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake