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

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.