Synthesis of 3,3-Dialkyl-Substituted Isoindolinones Enabled by Nickel-Catalyzed Reductive Dicarbofunctionalization of Enamides

Herein we report the nickel-catalyzed reductive dicarbofunctionalization of 1,1-disubstituted enamides with unactivated alkyl iodides to access the 3,3-dialkyl-substituted isoindolinone frameworks. This tandem cyclization/reductive coupling protocol exhibits broad functional group tolerance under mild conditions. The utilization of commercially accessible chiral Bn-Biox ligand allows excellent enantioselectivities to forge the tetrasubstituted stereocenters.

Automated summary

A novel nickel-catalyzed reaction method for the synthesis of 3,3-dialkyl-substituted isoindolinone frameworks from unactivated alkyl iodides and 1,1-disubstituted enamides has been reported. The method exhibits good functional group tolerance and enantioselectivity through the use of commercially available chiral Bn-Biox ligand.