Ligand-Enabled Carboamidation of Unactivated Alkenes through Enhanced Organonickel Electrophilicity

Catalytic carboamination of alkenes is a powerful synthetic tool to access valuable amine scaffolds from abundant and readily available alkenes. Although a number of synthetic approaches have been developed to achieve the rapid buildup of molecular complexity in this realm, the installation of diverse carbon and nitrogen functionalities onto unactivated alkenes remains underdeveloped. Here we present a ligand design approach to enable nickel-catalyzed three-component carboamidation that is applicable to a wide range of alkenyl amine derivatives via a tandem process involving alkyl migratory insertion and inner-sphere metal-nitrenoid transfer. With this method, various nitrogen functionalities can be installed into both internal and terminal unactivated alkenes, leading to differentially substituted diamines that would otherwise be difficult to access. Mechanistic investigations reveal that the tailored Ni(cod)(BQ(iPr)) precatalyst modulates the electronic properties of the presumed pi-alkene-nickel intermediate via the quinone ligand, leading to enhanced carbonickelation efficiency across the unactivated C=C bond. These findings establish nickel's ability to catalyze multicomponent carboamidation with a high efficiency and exquisite selectivity.

Automated summary

This study presents a ligand design approach for nickel-catalyzed three-component carboamidation, which is applicable to the synthesis of alkenyl amine derivatives. With this method, diverse nitrogen functionalities can be installed onto unactivated alkenes, leading to differentially substituted diamines.