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Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand

Zheqi Li, Hongjin Shi, Xueying Chen, Long Peng, Yuqiang Li, Guoyin Yin

2023Journal of the American Chemical Society45 citationsDOI

Abstract

Chiral boronic esters are a class of versatile building blocks. We describe herein an asymmetric nickel-catalyzed borylative coupling of terminal alkenes with nonactivated alkyl halides. The success of this asymmetric reaction is ascribed to the application of a chiral anionic bisoxazoline ligand. This study provides a three-component strategy to access α- and β-stereogenic boronic esters from easily accessible starting materials. This protocol is characterized by mild reaction conditions, wide substrate scope and high regio- and enantioselectivity. We also showcase the value of this method in simplifying the synthesis of several drug molecules. Mechanistic studies suggest that the generation of enantioenriched boronic esters bearing an α-stereogenic center results from a stereoconvergent process, while the enantioselectivity-controlling step in the generation of boronic esters with a β-stereocenter is switched to the olefin migratory insertion step due to coordination of an ester group.

Topics & Concepts

ChemistryStereocenterEnantioselective synthesisAlkylLigand (biochemistry)Combinatorial chemistryBoronic acidOrganic chemistryCatalysisBiochemistryReceptorOrganoboron and organosilicon chemistryCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling Reactions
Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand | Litcius