An Umpolung Approach for C2-Selective C−H Amination of Azines by Palladium Catalysis

Abstract

The site-selective C−H amination of azines is a critical challenge due to the broad applications of amino azines in biologically important compounds. In this work, we report a conceptually novel approach to the electrophilic C2-selective C−H amination of azines using O-benzoylhydroxylamines, catalyzed by a benzyl–palladium complex. A key feature of this transformation is the formation of the distal C−N bond via a benzyl–Pd intermediate, facilitated by a malonate substituent on the azine as a remote directing group. This strategy effectively overrides the inherent polarity mismatch typically observed in electrophilic C2-C−H aminations. The reaction exhibits high site-selectivity and demonstrates towards amine-sensitive functional group, highlighting its synthetic utility.