Carbonyl 1,2-transposition through triflate-mediated α-amination.

Abstract

To date, it remains challenging to selectively migrate a carbonyl oxygen within a given molecular scaffold, especially to an adjacent carbon. In this work, we describe a simple one- or two-pot protocol that transposes a ketone to the vicinal carbon. This approach first converts the ketone to the corresponding alkenyl triflate, which can then undergo the palladium- and norbornene-catalyzed regioselective α-amination and ipso-hydrogenation enabled by a bifunctional hydrogen and nitrogen donor. The resulting “transposed enamine” intermediate can subsequently be hydrolyzed to produce the 1,2-carbonyl–migrated product. This method allows rapid access to unusual bioactive analogs through late-stage functionalization.