Li Yan-Bo, Xu Minghao, Kellermann Leopold A, Erchinger Johannes E, Dutta Subhabrata, Daniliuc Constantin G, Qi Xiaotian, Glorius Frank
Organisch-Chemisches Institut, Universität Münster, Münster 48149, Germany.
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.
J Am Chem Soc. 2025 Jan 22;147(3):2642-2652. doi: 10.1021/jacs.4c14913. Epub 2025 Jan 8.
Nozaki-Hiyama-Kishi (NHK) reactions offer a mild approach for the formation of alcohol motifs through radical-polar crossover-based pathways from various radical precursors. However, the application of multicomponent NHK-type reactions, which allow the formation of multiple bonds in a single step, has been largely restricted to bulky alkyl radical precursors, thus limiting their expanded utilization. Herein, we disclose a general three-component NHK-type reaction enabled by delayed radical-polar crossover, which efficiently tolerates a plethora of radical precursors that were previously unavailable. This method enables the modular assembly of versatile homoallylic alcohols from feedstock chemicals with excellent chemo-, regio-, diastereo-, and enantioselectivities in a single step. Experimental studies and density functional theory (DFT) calculations reveal that the kinetically favored formation of an allylchromium(III) species is paramount for enforcing the delayed radical-polar crossover over direct radical addition. Finally, straightforward transformations and applications of the homoallylic alcohol products were demonstrated, showcasing the synthetic utility of this method.
野崎-日山-岸（NHK）反应提供了一种温和的方法，可通过基于自由基-极性交叉的途径，从各种自由基前体形成醇基序。然而，多组分NHK型反应（允许在一步中形成多个键）的应用在很大程度上仅限于体积较大的烷基自由基前体，因此限制了它们的广泛应用。在此，我们公开了一种通过延迟自由基-极性交叉实现的通用三组分NHK型反应，该反应能有效耐受大量以前无法使用的自由基前体。该方法能够在一步中从原料化学品模块化组装通用的高烯丙醇，具有出色的化学、区域、非对映和对映选择性。实验研究和密度泛函理论（DFT）计算表明，动力学上有利的烯丙基铬（III）物种的形成对于强制延迟自由基-极性交叉而非直接自由基加成至关重要。最后，展示了高烯丙醇产物的直接转化和应用，突出了该方法的合成实用性。
