Cu-Catalyzed Three-Component Alkene Carboamination: Mechanistic Insights and Rational Design to Overcome Limitations.

Herein, we report mechanistic investigations into the Cu-catalyzed three-component carboamination of alkenes with α-halo carbonyls and aryl amines via an oxocarbenium intermediate. Monitoring the reaction reveals the formation of transient atom transfer radical addition (ATRA) intermediates with both electron-neutral and deficient vinyl arenes as well as unactivated alkenes. Based on our experimental studies and density functional theory calculations, the oxocarbenium is generated through atom transfer and subsequent intramolecular substitution. Further, mechanistic factors that dictate the regioselectivity of the nucleophilic attack onto the oxocarbenium to afford the γ-amino ester, γ-iminolactone, or γ-lactone are discussed. A strategy to overcome scope limitation with respect to unactivated alkenes is developed using the mechanistic insights gained herein. Finally, we demonstrate that under modified conditions, our Cu catalyst enables the ATRA reaction between a variety of alkyl halides and vinyl arenes/α-olefins, and we present a one-pot, two-step carbofunctionalization with an array of nucleophiles through ATRA/SN2.

Palladium and Iron Cocatalyzed Aerobic Alkene Aminoboration.

Aminoboration of simple alkenes with nitrogen nucleophiles remains an unsolved problem in synthetic chemistry; this transformation can be catalyzed by palladium via aminopalladation followed by transmetalation with a diboron reagent. However, this catalytic process faces inherent challenges with instability of the alkylpalladium(II) intermediate toward ß-hydride elimination. Herein, we report a palladium/iron cocatalyzed aminoboration, which enables this transformation. We demonstrate these conditions on a variety of alkenes and norbornenes with an array of common nitrogen nucleophiles. In the developed strategy, the iron cocatalyst is crucial to achieving the desired reactivity by serving as a halophilic Lewis acid to release the transmetalation-active cationic alkylpalladium intermediate. Furthermore, it serves as a redox shuttle in the regeneration of the Pd(II) catalyst by reactivation of nanoparticulate palladium.