Rh‐Catalyzed Chemodivergent Parallel Kinetic Resolution and Desymmetrization of Enynes and Dienynes with Acrylamides

Catalytic enantioselective synthesis of structurally diverse 3D molecules remains a central challenge in organic chemistry. Intermolecular chemodivergent parallel kinetic resolution (PKR) of racemic substrates through C─C bond formation using a single catalyst to yield distinct products is rare. Here, we report Rh-catalyzed chemodivergent PKR of racemic 1,6-enynes with α-fluoroacrylamides or mixtures of different acrylamides, proceeding via 2+2+2 cycloaddition and C-H alkylation to afford structurally and stereochemically distinct products with high selectivity under mild conditions. Additionally, substituent-dependent enantioselective desymmetrization of symmetric dienynes was achieved. Computational studies revealed that, depending on the stereochemistry of the 1,6-enyne, steric repulsion between the ligand and the enyne favors a compact C-H activation transition state, whereas its absence favors a C═C insertion transition state involving a smaller bond dissociation energy. These findings establish a versatile catalytic platform for the selective generation of 3D molecular complexity, advancing diversity-oriented synthesis from racemic or symmetric precursors.