Researchers have developed a photochemical platform using enamino ketones to overcome selectivity constraints in the de Mayo reaction, according to a paper published in Nature Communications on Aug. 25, 2026. The method directly furnishes cyclohexenone derivatives and expands access to 1,5-diketone structures used in pharmaceutical discovery.
Chemists use de Mayo reactions as a photochemical tool for skeletal editing, rapidly synthesizing 1,5-dicarbonyl compounds by adding 1,3-dicarbonyl units across olefins. However, traditional versions suffer from narrow regio- and chemoselectivity. Reaction mixtures cannot selectively install distinct aryl groups on 1,5-diketones. In 1-aryl-5-alkyl diketones, substituents consistently favor the α-position of the aryl ketone. Additionally, electron-withdrawing groups from deficient olefins generally remain restricted to the 3-position. Deficient olefins also favor unwanted radical addition and formal redox pathways over the intended transformation.
Enamino ketones overcome these reaction barriers under practical conditions. By adjusting the N-protecting group and introducing a chiral Brønsted acid catalyst, the team achieved a proof-of-concept kinetic resolution of the imine intermediate that forms after [2 + 2] cycloaddition.
Authors Wenle Zhu and Xin Sun contributed equally to the paper, collaborating with Dong Tian, Xiaowei Zhao, Zhiyong Jiang, and Shanshan Cao. The research team spans Henan University, Henan Normal University's Pingyuan Laboratory, and Xinjiang Normal University. Financial support came from the National Natural Science Foundation of China, the Central Government Guided Local Science and Technology Development Fund Projects, the Outstanding Foreign Scientists’ Studio of Henan Province, and the Henan Provincial Natural Science Foundation.
