Mapping Electrophile Chemoselectivity in DalPhos/Nickel N‐Arylation Catalysis: The Unusual Influence of Remote Sterics

Abstract

We disclose herein our evaluation of competitive (hetero)aryl‐X (X: Br > Cl > OTf) reactivity preferences in bisphosphine/Ni‐catalyzed C‐N cross‐coupling catalysis, using furfurylamine as a prototypical nucleophile, and employing DalPhos and DPPF as representative ancillary ligands with established efficacy. Beyond this general (pseudo)halide ranking, other intriguing structure‐reactivity trends were noted experimentally, including the unexpected observation that bulky alkyl (e.g., R = tBu) substitution in para‐R‐aryl‐X electrophiles strongly discourages (pseudo)halide reactivity relative to smaller substituents (e.g., nBu, Et, Me), despite being both remote from, and having a similar electronic influence on, the reacting C‐X bond; such effects on nickel oxidative addition have not been documented previously and were not observed in our comparator reactions presented herein involving palladium. Density functional theory modeling of such PhPAd‐DalPhos/Ni‐catalyzed C‐N cross‐couplings revealed the origins of competitive turnover of C‐Br over C‐Cl, and possible ways in which bulky para‐alkyl substitution might discourage net electrophile uptake/turnover, leading to inversion of halide selectivity.