Ligand-Enabled Nickel Catalysis for the O-Arylation of Alcohols and Phenols with (Hetero)aryl Chlorides Using a Soluble Organic Base

While ligand-enabled metal-catalyzed cross-coupling has emerged as a versatile approach to thermal C(sp(2))-O bond formation, broadly effective catalysts capable of employing a soluble organic base have yet to be disclosed. We report, such a Ni-based catalyst system for the O-arylation of both aliphatic alcohols and phenols, that makes use of PAd2-DalPhos ligation and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or tert-butylimino-tri(pyrrolidino)phosphorane (BTPP) as the base, in combination with a halide scavenger (sodium trifluoroacetate, NaTFA). This methodology affords a broad and expanded scope of (hetero)aryl ether products derived from inexpensive and widely available (hetero)aryl chlorides in a manner that is competitive with the best O-arylation catalysts reported to date for such electrophiles. Successful transformations of base-sensitive substrates that are incompatible with commonly employed NaOtBu are presented, as are competition studies revealing a complex interplay of the electrophile, nucleophile, and organic base in directing selectivity for the O-arylation of aliphatic alcohols versus phenols.