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

Chiral boronic esters are a class of versatile building blocks.We describe herein an asymmetric nickel-catalyzed borylative couplingof terminal alkenes with nonactivated alkyl halides. The success ofthis asymmetric reaction is ascribed to the application of a chiralanionic bisoxazoline ligand. This study provides a three-componentstrategy to access alpha- and beta-stereogenic boronic estersfrom easily accessible starting materials. This protocol is characterizedby mild reaction conditions, wide substrate scope and high regio-and enantioselectivity. We also showcase the value of this methodin simplifying the synthesis of several drug molecules. Mechanisticstudies suggest that the generation of enantioenriched boronic estersbearing an alpha-stereogenic center results from a stereoconvergentprocess, while the enantioselectivity-controlling step in the generationof boronic esters with a beta-stereocenter is switched to the olefinmigratory insertion step due to coordination of an ester group.

Automated summary

Chiral boronic esters can be synthesized through an asymmetric nickel-catalyzed borylative coupling reaction between alkyl halides and terminal alkenes. The use of a chiral bisoxazoline ligand enables this reaction to proceed with high regio- and enantioselectivity. This method offers a three-component strategy for accessing alpha- and beta-stereogenic boronic esters from readily available starting materials. Additionally, it simplifies the synthesis of several drug molecules.