Iodine(I)/Iodine(III) Catalysis on the Asymmetric 1,4‐Difluorination of Z/E ‐Dienes: Mechanism, Selectivity Control, and Catalyst Effects

The iodine(I)/iodine(III) catalytic cycle, which serves as an effective approach for organic transformations, has exhibited catalytic activity comparable to that of transition metals while boasting superior sustainability and resource efficiency. In this work, we have combined quantum chemical calculations with experimental validation to establish a comprehensive mechanistic framework for iodine(I)/iodine(III)‐catalyzed diene difluorination, clarifying the regio‐, stereo‐, and enantioselectivity in this transformation. Computational studies reveal that the E ‐isomer product is preferentially generated from Z/E ‐dienes under ambient temperature. The reaction displays prominent regioselectivity, with 1,4‐difluorination much more favorable than the 1,2‐regioisomeric pathway. Chiral iodine(I)/iodine(III) catalysis studies show that all tested chiral halogen bond catalysts favor the formation of the S ‐enantiomer (96% e.e. , catl.). Further analysis indicated that the synergistic effects of electrostatic interactions and strong hydrogen bonds play a key role in promoting the preferential generation of the S ‐enantiomer. Experimental observations confirm that the difluorination reaction proceeds with excellent enantioselectivity ( S ‐enantiomer 92% e.e. , exp.) and 1,4‐regioselectivity, with the difluorinated E ‐isomer product as the major product. These findings advance the fundamental understanding of halogen bond‐driven asymmetric catalysis and highlight the great potential of iodine(I)/iodine(III) catalysts as sustainable alternatives to transition metal catalysts.