Ligand‐Controlled Regiodivergence in Nickel‐Catalyzed Hydroarylation and Hydroalkenylation of Alkenyl Carboxylic Acids

• Published in: Angewandte Chemie International Edition Vol. 59; no. 51; pp. 23306 - 23312
• Main Authors: Li, Zi‐Qi, Fu, Yue, Deng, Ruohan, Tran, Van T., Gao, Yang, Liu, Peng, Engle, Keary M.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 14.12.2020; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: alkene functionalization; Alkenes - chemistry; Carboxylic acids; Carboxylic Acids - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; cross-coupling; Density Functional Theory; Hydrocarbons - chemical synthesis; Hydrocarbons - chemistry; hydrofunctionalization; Ligands; Molecular Structure; Nickel; Nickel - chemistry; Physical Sciences; regiodivergence; Regioselectivity; Science & Technology; Selectivity; Stereoisomerism; Steric effects; Yield; OXIDATION; nickel; PALLADIUM; STYRENES; MECHANISM; alkene functionalization; UNACTIVATED ALKENES; FUNCTIONALIZATION; regiodivergence; ESTERS; cross-coupling; hydrofunctionalization; SELECTIVE HYDROARYLATION; ALKYLBORATION; CYCLIZATION
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202010840

A nickel‐catalyzed regiodivergent hydroarylation and hydroalkenylation of unactivated alkenyl carboxylic acids is reported, whereby the ligand environment around the metal center dictates the regiochemical outcome. Markovnikov hydrofunctionalization products are obtained under mild ligand‐free conditions, with up to 99 % yield and >20:1 selectivity. Alternatively, anti‐Markovnikov products can be accessed with a novel 4,4‐disubstituted Pyrox ligand in excellent yield and >20:1 selectivity. Both electronic and steric effects on the ligand contribute to the high yield and selectivity. Mechanistic studies suggest a change in the turnover‐limiting and selectivity‐determining step induced by the optimal ligand. DFT calculations reveal that in the anti‐Markovnikov pathway, repulsion between the ligand and the alkyl group is minimized (by virtue of it being 1° versus 2°) in the rate‐ and regioselectivity‐determining transmetalation transition state. A novel 4,4‐disubstituted Pyrox ligand overrides innate regioselectivity trends in the Ni‐catalyzed hydroarylation and alkenylation of alkenyl carboxylic acids. This method enables regiodivergent entry to β‐ and γ‐functionalized aliphatic acids.