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Dispersion-Driven Ligand Design for Cu(II)/Bis(oxazoline)-Catalyzed Asymmetric IEDDA Reactions
Feiyang Li1, Minjie Bi1, Lixin Cui1
1Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Zhejiang Key Laboratory of Organosilicon Material Technology, College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, 2318 Yuhangtang Road, Hangzhou 311121, Zhejiang, China.
Abstract:
The strategic exploitation of attractive London dispersion interactions in asymmetric catalysis, while not without precedent, has yet to become a mainstream design principle. Herein, we report a dispersion-driven ligand strategy that simultaneously enhances both efficiency and stereoselectivity in the chiral Cu(II)/bis(oxazoline)-catalyzed IEDDA reaction between 1,3-cyclohexadienes (CHDs) and 2-pyrones. Strategic incorporation of a tert-butyl group into the ligand framework enabled significant attractive dispersion interactions, which concurrently (i) increased the stereomeric transition state energy gap (ΔΔG⧧) and (ii) decreased the reaction barrier (ΔG⧧). A combined energy decomposition analysis (EDA) and independent gradient model (IGMH) study quantitatively decoupled these interactions, unequivocally establishing their critical roles in governing stereocontrol.
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