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Ligand‐Dictated Regiodivergent Allylic Functionalizations via Palladium‐Catalyzed Remote Substitution

Xin Wang, Han‐Zhe Miao, Guo‐Qiang Lin, Zhi‐Tao He

2023Angewandte Chemie International Edition24 citationsDOI

Abstract

Abstract Different from classical allylic substitutions that require a vicinal leaving group, an olefin bearing a remote leaving group is scarcely viewed as a potential allylation substrate. Herein, we describe feasible protocols to achieve regiodivergent allylic C−H functionalizations via palladium‐catalyzed remote substitution, which provides a novel strategy for the seldomly studied migratory Tsuji–Trost reaction. Dictated by a suitable ligand, a process that involved 4,3‐hydrofunctionalization of the generated conjugated diene intermediate via metal walking is observed in generally >20 : 1 regioselectivity. Unexpectedly, a related 1,4‐hydrofunctionalization pathway is found to be a major route with a newly synthesized electron‐rich bisphosphine ligand, which challenges the conventional viewpoint on the potential regioselectivity of hydrofunctionalizations of linear internal conjugated dienes via η 3 ‐substitution. A series of deuterium experiments and kinetic studies provide a preliminary insight into the potential catalytic cycle.

Topics & Concepts

RegioselectivityAllylic rearrangementLigand (biochemistry)ChemistryPalladiumVicinalStereochemistryCatalysisSubstitution reactionOlefin fiberCombinatorial chemistryOrganic chemistryReceptorBiochemistryCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and CatalysisAsymmetric Synthesis and Catalysis
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