Catalytic dehydrogenative synthesis of α,β-unsaturated secondary amides without external oxidants

Abstract

Direct dehydrogenative synthesis of α,β-unsaturated secondary amides still represents an elusive transformation. Herein we describe a palladium-catalyzed redox-neutral desaturation to prepare α,β-conjugated secondary amides. Without external oxidants, this approach relies on the N–O bond cleavage as the driving force to achieve formal dehydrogenation. Complementary to known protocols, this transformation is enabled by the unique reactivity of hydroxamate, thereby representing a novel strategy to accomplish carbonyl desaturation. Desired conjugated secondary amides can be efficiently synthesized in the presence of more reactive esters and even ketones, thus providing a solution to the long-standing issue of α,β-unsaturated secondary amides via C–C desaturation.