Analysis reveals how chiral counteranions enhance enantio- and diastereoselectivity in photoredox catalysis, suggesting new design strategies.
We investigate the origin of stereocontrol in asymmetric counteranion-directed photoredox catalysis (ACPC) using a representative [2+2] cycloaddition mediated by a chiral IDPi counteranion (Science 2023, 379, 494–499). Combining extensive conformational sampling, high-level DFT calculations, and multiscale modeling, we elucidate the mechanism and stereochemical landscape of this transformation. Both enantio- and diastereoselectivity are established in the first C–C bond-forming step: diastereoselectivity arises from intrinsic aryl–aryl interactions within the radical cation–styrene pair, whereas enantioselectivity is imposed by the confined chiral environment of the IDPi counteranion. Although electronically silent during the initial photoinduced single-electron transfer, the counteranion anchors the radical cation and organizes its cycloaddition with styrene. Atomic decomposition of the London dispersion (ADLD) and molecular dispersion potential (MDP) analyses reveal that attractive van der Waals forces, shaped by the steric and electronic architecture of the counteranion, promote reactive prealignment of the substrates and selectively stabilize the transition state leading to the major product. These findings provide a unified framework for stereocontrol in chiral ion-pair radical catalysis and offer general strategies for designing asymmetric photoredox transformations.
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Baldinelli et al. (2025) studied this question.
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