Photocatalytic Stereoselective Editing of Alkynes to 3D Molecules via Hydrogen Atom Transfer-Mediated Dynamic Epimerization

Three-dimensional molecules have drawn tremendous attention due to their pivotal roles in drug discovery as saturated bioisosteres of benzenoids. The direct construction of these scaffolds from simple and readily available one-dimensional building blocks is highly attractive but challenging. This study presents a concise synthesis of bicyclo[2.2.1]heptanones and bicyclo[3.2.1]octanones via a photoinduced decatungstate-catalyzed bicyclization of internal alkynes with aldehydes. The reaction enables simultaneous formation of four chemical bonds and two carbocycles, demonstrating excellent site-, regio-, and diastereoselectivity. Experimental and theoretical investigations suggest that the initial cyclization produces a cyclopentanone intermediate with poor diastereoselectivity, and an uncommon dynamic kinetic resolution enabled by hydrogen atom transfer-mediated C-H epimerization yields bicyclic products with excellent diastereoselectivity. This method represents an in situ concurrent editing of skeleton and stereochemistry, which exhibits great potentials for increasing molecular diversity and complexity and changing the way to assemble biologically important compounds. Three-dimensional molecules have drawn tremendous attention due to their pivotal roles in drug discovery as saturated bioisosteres of benzenoids. Here, the authors present a concise synthesis of bicyclo[2.2.1]heptanones and bicyclo[3.2.1]octanones via a photoinduced decatungstate-catalyzed bicyclization of internal alkynes with aldehydes.