A redox-enabled strategy for intramolecular hydroamination

Abstract

Metal- or acid-catalyzed intramolecular hydroamination and Cope-type intramolecular hydroamination, a distinct concerted approach using hydroxylamines, typically suffer from significant synthetic limitations. Herein we report a process for intramolecular hydroamination that uses a redox-enabled strategy relying on efficient in situ generation of hydroxylamines by oxidation, followed by Cope-type hydroamination, then reduction of the resulting pyrrolidine N-oxide. The steps are performed sequentially in a single pot, no catalyst is required, the conditions are mild, the process is highly functional group tolerant, and no chromatography is generally required for isolation. A robustness screen and a gram-scale example further support the practicality of this approach.