立体中心
化学
吡咯烷
烷基
哌啶
芳基
动力学分辨率
组合化学
氧化还原
卤素
芳基
还原消去
自由基离子
立体化学
小学(天文学)
羟基化
有机化学
立体选择性
作者
Yu Wang,Jiawei Sun,Yin Li,David A. Cagan,Oliver T. Ring,Xin Zeng,Jet Tsien,Luca Massaro,Jillian E. Smith,Brandon J. Orzolek,Michael R. Collins,Yu Kawamata,Phil S. Baran
出处
期刊:Science
[American Association for the Advancement of Science]
日期:2026-06-04
卷期号:392 (6802): 1075-1081
被引量:1
标识
DOI:10.1126/science.aef6981
摘要
) bonds through cross-coupling remains a formidable challenge owing to competing β-hydride elimination and homocoupling as well as the poor inherent stereocontrol of radical pathways. In this work, we report a scalable stereoretentive radical-radical cross-coupling of two distinct, transient alkyl radicals, derived from enantioenriched sulfonylhydrazides and achiral primary and secondary alkyl halides, achieved without chiral ligands, directing groups, or exogenous redox agents. This substrate-controlled approach leverages a nickel-catalyzed, redox-neutral manifold, which enables precise kinetic matching of diazene-mediated radical generation and halogen atom transfer. The reaction produced enantiospecificities of 80 to 96% and synthetically useful yields (up to 90%) across diverse piperidine and pyrrolidine scaffolds while tolerating ethers, free amines, aryl halides, heterocycles, olefins, and other sensitive motifs. Mechanistic studies support caged radical rebound at nickel to preserve chirality, followed by nickel(I)-nickel(III)-mediated radical capture and reductive elimination.
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