Functional Group Tolerant Nickel-Catalyzed Cross-Coupling Reaction for Enantioselective Construction of 30 Methyl-Bearing Stereocenters

摘要

The first Negishi nickel-catalyzed stereospecific cross-coupling reaction of secondary benzylic esters is reported. A series of traceless directing groups are evaluated for ability to promote cross-coupling with dimethylzinc. Esters with a chelating thioether derived from commercially-available 2-(methylthio)acetic acid are most effective. The products are formed in high yield and with excellent stereospecificity. A variety of functional groups are tolerated in the reaction including alkenes, alkynes, esters, amines, imides, and O-, S-, and N-heterocycles. The utility of this transformation is highlighted in the enantioselective synthesis of a retinoic acid receptor (RAR) agonist and a fatty acid amide hydrolase (FAAH) inhibitor.