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Chemoselective Cu-Catalyzed Cross-Nucleophile Alkylarylation of Alkenes

SangHyun Lee, Jianyang D. Yu, Alex L. Monterde, S TUNG, Ya‐Nong Wang, Brittany L. Gay, Kami L. Hull

2024ACS Catalysis11 citationsDOIOpen Access PDF

Abstract

We report a general cross-nucleophile alkene alkylarylation that adds two different boronic acids, an alkyl and an aryl, across a vinylarene to afford 1,1-diarylalkanes. The high chemoselectivity originates from the distinct reactivities of the two boronic acids: the alkylboronic acid is selectively oxidized to an alkyl radical, while the arylboronic acid favors transmetalation with the Cu(II) catalyst. Mechanistic studies suggest that Lewis acid–Lewis base interactions between in situ generated boroxines and added amine are critical for selectivity. A scope of 37 examples is presented with structurally and electronically diverse alkyl, vinyl, and aryl coupling partners. The synthetic utility is demonstrated in the preparation of pimozide and anticancer agent analogues.

Topics & Concepts

CatalysisNucleophileChemistryChemoselectivityOrganic chemistryCombinatorial chemistryCatalytic C–H Functionalization MethodsRadical Photochemical ReactionsFluorine in Organic Chemistry