德国亚琛工业大学Schoenebeck, Franziska团队报道了基于金属自由基的乙烯基环丙烷动态立体变化。相关研究成果于2024年6月19日发表于国际一流学术期刊《自然》。

在化学过程中，对更大可持续性和更低能源使用不断增加的需求，要求采用全新的方法和反应原理。

在这种情况下，在不太贵的金属中奇数氧化态的显著流行，通过金属自由基催化具有根本不同反应模式的未开发潜力。与公认的反应性范式相反，即有机自由基在加入乙烯基环丙烷后，会在应变释放下导致快速开环——这一转变广泛用作自由基中介作用的机制探针（自由基时钟）——该文中表明，金属基自由基，即Ni（I）金属自由基，会触发可逆的顺式/反式异构化，而不是开环。异构化在手性反转下进行，根据取代模式，只需要添加非贵催化剂，在室温下不到5分钟发生。

研究人员综合计算和实验机制研究解释了金属自由基催化作为这种深刻反应的起源，合理化了观察到的立体反转，并揭示了该过程的关键反应特征，包括其可逆性。这些见解使对映纯顺式/反式混合物能够通过多个Ni（I）催化轮次向单个非对映异构体进行迭代热力学富集，并扩展到二乙烯基环丙烷，这构成了天然产物和总合成物中的战略基序。

虽然反式异构体通常需要在约200°C下加热，以在外消旋作用下引发热异构化，生成顺式二乙烯基环丙烷，然后进行简单的Cope型重排，但该文显示，类似的反热力学过程在温和条件下在Ni（I）金属自由基催化下进行，不会失去任何立体化学完整性，从而能够温和且立体化学纯地进入七元环、稠环系统和螺环。

附：英文原文

Title: Dynamic stereomutation of vinylcyclopropanes with metalloradicals

Author: Mendel, Marvin, Karl, Teresa M., Hamm, Jegor, Kaldas, Sherif J., Sperger, Theresa, Mondal, Bhaskar, Schoenebeck, Franziska

Issue&Volume: 2024-06-19

Abstract: The ever increasing demands for greater sustainability and lower energy usage in chemical processes call for fundamentally new approaches and reactivity principles. In this context, the pronounced prevalence of odd-oxidation states in less precious metals bears untapped potential for fundamentally distinct reactivity modes via metalloradical catalysis1,2,3. Contrary to the well-established reactivity paradigm that organic free radicals, upon addition to a vinylcyclopropane, lead to rapid ring opening under strain release—a transformation that serves widely as a mechanistic probe (radical clock)4 for the intermediacy of radicals5—we herein show that a metal-based radical, that is, a Ni(I) metalloradical, triggers reversible cis/trans isomerization instead of opening. The isomerization proceeds under chiral inversion and, depending on the substitution pattern, occurs at room temperature in less than 5min, requiring solely the addition of the non-precious catalyst. Our combined computational and experimental mechanistic studies support metalloradical catalysis as origin of this profound reactivity, rationalize the observed stereoinversion and reveal key reactivity features of the process, including its reversibility. These insights enabled the iterative thermodynamic enrichment of enantiopure cis/trans mixtures towards a single diastereomer through multiple Ni(I) catalysis rounds and also extensions to divinylcyclopropanes, which constitute strategic motifs in natural product- and total syntheses6. While the trans-isomer usually requires heating at approximately 200°C to trigger thermal isomerization under racemization to cis-divinylcyclopropane, which then undergoes facile Cope-type rearrangement, the analogous contra-thermodynamic process is herein shown to proceed under Ni(I) metalloradical catalysis under mild conditions without any loss of stereochemical integrity, enabling a mild and stereochemically pure access to seven-membered rings, fused ring systems and spirocycles.

DOI: 10.1038/s41586-024-07555-1

Source: https://www.nature.com/articles/s41586-024-07555-1