Enantioselective Copper-Catalyzed Synthesis of Hydroxylamines via Hydrofunctionalization of Alkenes using Nitroalkanes

Abstract

Herein, we report that nitroalkanes are competent electrophiles for the enantioselective copper hydride (CuH)-catalyzed alkene hydrofunctionalization of vinyl(hetero)arenes to generate hydroxylamines in good yields and with high levels of enantioselectivity. Control experiments and density functional theory (DFT) calculations suggest that the nitro group constitutes the active electrophile. The direct addition of the enantioenriched alkyl copper intermediate to the nitro group outcompetes competitive reduction or deprotonation of the nitroalkane. DFT calculations indicate that the addition of the stereoenriched alkyl copper intermediate to nitroalkane electrophiles occurs through a six-membered cyclic transition state featuring dearomatization of the vinyl arene. Overall, this process constitutes a one-step route to access enantioenriched N-alkylhydroxylamine from vinylarenes and nitroalkanes.