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Light-empowered contra-thermodynamic stereochemical editing

Abstract

Creating, conserving and modifying the stereochemistry of organic compounds has been the subject of significant research efforts in synthetic chemistry. Most synthetic routes are designed according to the stereoselectivity-determining step. Stereochemical editing is an alternative strategy, wherein the chiral-defining or geometry-defining steps are independent of the construction of the major scaffold or complexity. It enables late-stage alterations of stereochemistry and can generate isomers from a single compound. However, in many instances, stereochemical editing processes are contra-thermodynamic, meaning the transformation is unfavourable. To overcome this barrier, photocatalysis uses photogenerated radical species and introduces thermochemical biases. A range of synthetically valuable contra-thermodynamic stereochemical editing processes have been invented, including deracemization of chiral molecules, positional alkene isomerization and dynamic epimerization of sugars and diols. In this Review, we highlight the fundamental mechanisms of visible-light photocatalysis and the general reactivity modes of the photogenerated radical intermediates towards contra-thermodynamic stereochemical editing processes.

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Fig. 1: Stereoselective synthesis by stereochemical logic or by stereochemical editing.
Fig. 2: Photochemical deracemization of alkenes.
Fig. 3: Visible light-induced deracemization of centrally chiral cyclopropanes by triplet sensitization.
Fig. 4: Visible light-driven enantiodivergent alkene reduction and deracemization of chiral aldehydes.
Fig. 5: Photochemical deracemization by sequential SET, proton transfer and HAT.
Fig. 6: Photoinduced deracemization by HAT catalysis and dual catalysis.
Fig. 7: Photoinduced contra-thermodynamic positional isomerization of alkenes.
Fig. 8: Visible light-driven epimerization of sugars and diols.

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Acknowledgements

The authors are grateful for financial support from the National Natural Science Foundation of China (22171099, 21971081, 22171099, 91856119, 21772053, 21820102003 and 91956201), the Program of Introducing Talents of Discipline to Universities of China (111 Program, B17019) and the Excellent Doctoral Dissertation Cultivation Grant to P.-Z.W. from CCNU (2022YBZZ003). They also thank all of the anonymous referees for their invaluable suggestions and comments on preparing this manuscript.

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P.-Z.W. and J.-R.C. contributed to the literature search, the preparation of figures and writing of the article. All authors contributed to editing the manuscript prior to submission. W.-J.X. and J.-R.C. conceived and directed the project.

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Correspondence to Wen-Jing Xiao or Jia-Rong Chen.

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Wang, PZ., Xiao, WJ. & Chen, JR. Light-empowered contra-thermodynamic stereochemical editing. Nat Rev Chem 7, 35–50 (2023). https://doi.org/10.1038/s41570-022-00441-2

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