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

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journal contribution
posted on 19.02.2016, 05:44 authored by Hanna M. Wisniewska, Elizabeth C. Swift, Elizabeth R. Jarvo
The first Negishi nickel-catalyzed stereospecific cross-coupling reaction of secondary benzylic esters is reported. A series of traceless directing groups is 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 agonist and a fatty acid amide hydrolase inhibitor.

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