Photocatalytic Carbonyl Alkylative Amination via Direct C-H Functionalization
Vaishnavi N Nair1, Madhu Sudan Manna1, Tiffany A Brisco1
1Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
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Amines are ubiquitous in bioactive molecules, yet their streamlined synthesis from simple precursors remains a longstanding challenge. Here we report a photocatalytic three-component coupling of aldehydes, anilines and alkyl arenes to form the desired amines. This carbonyl alkylative amination proceeds through direct C-H functionalization of alkyl arenes, bypassing the need for preformed imines or organometallic reagents. The merger of visible-light photocatalysis with Lewis acid catalysis underpins the reaction's efficiency and broad scope, enabling rapid access to structurally diverse amines. Mechanistic studies elucidate key features of the activation pathway, while the development of an enantioselective variant using a chiral copper catalyst highlights the potential for asymmetric synthesis.
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