While the Ni-catalyzed cross-coupling of primary or secondary aliphatic alcohols and (hetero)aryl electrophiles is known, related crosscouplings involving tertiary aliphatic alcohols, with a broad scope, are challenging. Herein we disclose that a Ni II precatalyst featuring the ligand CgPhen-DalPhos is unusual in its ability to promote the C−O cross-coupling of tertiary aliphatic alcohols with (hetero)aryl halides (Cl, Br, and I) or phenol derivatives (OMs and OPiv). An exploration of substrate scope and competition experiments help to shed light on the capabilities and reactivity preferences of this catalyst system.

A systematic evaluation of competitive bisphosphine/Ni-catalyzed CÀ N versus CÀ O cross-couplings involving model compounds enabled development of hitherto unknown chemoselective O-and N-arylation of amino alcohols with (hetero)aryl chloride electrophiles, without recourse to protection group chemistry. Use of the CyPAd-DalPhos pre-catalyst C2 enabled particularly challenging O-arylation chemoselectivity in amino alcohols featuring branched primary and secondary alkylamine groups, while selective N-arylation was observed in substrates featuring less-hindered linear alkylamine and aniline reacting groups. Useful reaction scope in the (hetero)aryl chloride was achieved throughout, and the ability to conduct such transformations using benchtop handling of materials is demonstrated.

Transition-metal catalysis has been consequential in enabling carbon-heteroatom bond-forming reactions. Recent breakthroughs in Ni-catalyzed cross-couplings have offered competitive, and in some cases superior, reactivity to Pd- or Cu-based processes. Amidst the ongoing renaissance in this field, the Ni-catalyzed C-O cross-coupling of alcohols and (hetero)aryl (pseudo)halides has surfaced as an effective strategy for the synthesis of (hetero)aryl ethers. Methodologies to achieve such transformations tend to rely on one of three catalytic approaches: (i) thermal conditions often accompanied by ancillary ligand design tailored for Ni catalysis; (ii) the synergistic combination of photoredox and Ni catalysis; or (iii) electrochemically driven Ni catalysis. In some instances, these protocols have provided access to expanded C-O cross-coupling substrate scope, including the use of inexpensive and abundant electrophile coupling partners (e.g., (hetero)aryl chlorides). This Review aims to summarize recent progress in the development of Ni-catalyzed O-arylations of primary, secondary, and tertiary aliphatic alcohols, as well as phenols, with (hetero)aryl electrophiles.

A systematic competitive evaluation of the DalPhos ligand family in nickel-catalyzed N-arylation chemistry is reported, involving primary (linear and branched) and secondary alkylamines, as well as a primary five-membered heteroarylamine (aminopyrazole), in combination with a diverse set of test electrophiles and bases (NaOtBu, K 2 CO 3 , DBU/NaTFA). In addition to providing optimal ligand/catalyst identification, and bringing to light methodology limitations (e. g., unwanted CÀ O cross-coupling with NaOtBu), our survey enabled the development of the first efficient catalyst system for heteroatom-dense CÀ N cross-coupling of aminopyrazoles and related nucleophiles with (hetero)aryl chlorides by use of an amine 'dual-base' system.

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