Application of Diazaphospholidine/Diazaphospholene-Based Bisphosphines in Room-Temperature Nickel-Catalyzed C(sp²)–N Cross-Couplings of Primary Alkylamines with (Hetero)aryl Chlorides and Bromides

Abstract

We report herein on the synthesis and catalytic application of a family of o-phenylene-bridged bisphosphine ancillary ligands featuring a bulky N-heterocyclic phosphine (NHP) donor fragment paired with an adjacent PR2 donor group (R = alkyl, aryl), whereby the incorporation of phosphorus into either a saturated or unsaturated heterocyclic ring serves as a means of modulating the donicity of the NHP fragment. Screening of these ancillary ligands in representative nickel-catalyzed C(sp2)–N cross-coupling test reactions allowed for the identification of one variant, featuring a saturated NHP structure and an adjacent diphenylphosphino donor group (i.e., NHP-DalPhos), as being particularly effective in reactions involving primary alkylamines. Notably, application of the derived precatalyst (NHP-DalPhos)NiCl(o-tolyl) (C1) enabled the typically challenging monoarylation of structurally diverse primary alkylamines with (hetero)aryl chlorides or bromides at room temperature. Also described are the results of our comparative density functional theory computational analysis of nickel-catalyzed primary alkylamine C(sp2)–N cross-couplings employing PAd-DalPhos or NHP-DalPhos.