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

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 condi...

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Published inAngewandte 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
LanguageEnglish
Published WEINHEIM Wiley 14.12.2020
Wiley Subscription Services, Inc
EditionInternational ed. in English
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Summary: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.
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A previous version of this manuscript has been deposited on a preprint server
https://doi.org/10.26434/chemrxiv.12650009
ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202010840