Mild Divergent Semireductive Transformations of Secondary and Tertiary Amides via Zirconocene Hydride Catalysis

The mild catalytic partial reduction of amides to imines has proven to be a challenging synthetic transformation, with many transition metals directly reducing these substrates to amines. Herein, we report a mild, catalytic method for the semireduction of both secondary and tertiary amides via zirconocene hydride catalysis. Utilizing just 5 mol % of Cp2ZrCl2, the reductive deoxygenation of secondary amides is demonstrated to furnish a diverse array of imines in up to 94% yield with excellent chemoselectivity and without the need for glovebox handling. Moreover, a novel reductive transamination of tertiary amides is also achievable when the catalytic protocol is carried out in the presence of a primary amine at room temperature, providing access to an expanded assortment of imines in up to 98% yield. Through slight procedural tuning, the single-flask conversion of amides to imines, aldehydes, amines or enamines is feasible, including multicomponent syntheses.

Automated summary

A mild and catalytic method for the semireduction of both secondary and tertiary amides via zirconocene hydride catalysis is reported. The reduction of secondary amides gives a diverse array of imines in up to 94% yield with excellent chemoselectivity using just 5 mol % of Cp2ZrCl2, without the need for glovebox handling. Furthermore, a novel reductive transamination of tertiary amides is achieved in the presence of a primary amine at room temperature, providing access to an expanded assortment of imines in up to 98% yield. Through slight procedural tuning, the single-flask conversion of amides to imines, aldehydes, amines or enamines is feasible, including multicomponent syntheses.