Enantioselective Nickel-Catalyzed Reductive Aryl/Alkenyl-CyanoCyclization Coupling to All-Carbon Quaternary Stereocenters

An enantioselective nickel-catalyzed intramolecular reductive cross-coupling of C(sp2) electrophiles and cyano groupsis reported. Enantioenriched CN-containing all-carbon quaternary stereocenters are assembled by desymmetrizing cyclization ofaryl/alkenyl halide-tethered malononitriles. The use of an organic reductant, (EtO)2MeSiH, is crucial to the enantioselectivity andreactivity. Applications of the method are demonstrated through the synthesis of bioactive molecules and their cyanated analoguesand the total synthesis of the natural product diomuscinone. This study exhibits the potential of desymmetrizing reductive couplingstrategies to access structurally rigid and synthetically versatile molecules from readily available starting materials.

Automated summary

The study presents an enantioselective nickel-catalyzed intramolecular reductive cross-coupling reaction to assemble CN-containing all-carbon quaternary stereocenters by desymmetrizing cyclization of aryl/alkenyl halide-tethered malononitriles. The use of an organic reductant is crucial for the selectivity and reactivity, with demonstrated applications in the synthesis of bioactive molecules and natural products.