Copper-Catalyzed Cope-Type Hydroamination of Nonactivated Olefins toward Cyclic Nitrones: Scope, Mechanism, and Enantioselective Process Development.

The catalytic synthesis of cyclic nitrones, an important type of functional molecules for both synthetic chemistry and related fields, remains underdeveloped. Herein we report the copper-catalyzed Cope-type hydroamination of oximes with pendant nonactivated olefins, which enables facile access to a series of five- and six-membered cyclic nitrones under mild conditions. In this study, heterocycle-tethered oximes were employed in the Cope-type hydroamination reaction for the first time. High enantioselectivity was achieved for carbon-tethered γ,δ-vinyl oximes to afford enantioenriched five-membered cyclic nitrones. The results of preliminary mechanistic studies indicate a mononuclear catalytic species and a unified catalytic pathway over a large temperature range.