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Kinetic Resolution for 1,4-Spin-Center Shift-Based Reduction of Azaarene-Functionalized Secondary and Tertiary Allylic Alcohols

Xiangbin Bai, Jialu Yao, Mengbo Zhang, Jing Li, Wenxian Li, Xiaowei Zhao, Yanli Yin, Zhiyong Jiang

2025Journal of the American Chemical Society5 citationsDOI

Abstract

The spin-center shift (SCS) represents a highly effective strategy in the field of photoredox catalysis for the generation of radical intermediates. Owing to intrinsic mechanistic constraints, the reaction pathway primarily entails a 1,2-radical translocation event, concomitant with a two-electron ionic shift. In contrast, remote SCS events are exceedingly rare, and when observed, they typically exploit C═C bonds within aromatic systems, where aromatization serves as an important thermodynamic driving force for this challenging transformation. Here, we present a proof-of-concept demonstrating that simple olefins can function as effective C═C units to facilitate the elusive 1,4-SCS process. Under cooperative photoredox and chiral Brønsted acid catalysis, a broad range of racemic azaarene-functionalized secondary and tertiary allylic alcohols undergo highly efficient kinetic resolution through 1,4-SCS-based reduction. This chiral acid-mediated pathway promotes the selective removal of γ-alcohols in one enantiomer, furnishing the complementary enantiomer in satisfactory yield with good to excellent enantioselectivity. The synthetic and pharmaceutical value of these enantioenriched azaarene derivatives─together with the challenges in accessing them by conventional methods─highlights the impact of this approach. By introducing an unprecedented π-system platform for remote SCS, this work represents a conceptual advance that opens new avenues for SCS-driven synthetic transformations.

Topics & Concepts

ChemistryKinetic resolutionAllylic rearrangementAromatizationEnantiomerPhotoredox catalysisYield (engineering)Combinatorial chemistryCatalysisEnantiomeric excessEnantioselective synthesisComputational chemistryIonic bondingReduction (mathematics)OrganocatalysisKinetic energyOrganic chemistryResolution (logic)ArylPhotochemistryWork (physics)Range (aeronautics)Ionic liquidFunctional groupStereoisomerismHalogenationIntramolecular forceRadical Photochemical ReactionsCatalytic C–H Functionalization MethodsSulfur-Based Synthesis Techniques