Role of Electron-Deficient Olefin Ligands in a Ni-Catalyzed Aziridine Cross-Coupling To Generate Quaternary Carbons
Role of Electron-Deficient Olefin Ligands in a Ni-Catalyzed Aziridine Cross-Coupling To Generate Quaternary Carbons
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DOI：
10.1021/jacs.0c02237
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发表时间：
2020-05-13
影响因子：
15
通讯作者：
Doyle, Abigail G.
中科院分区：
文献类型：
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作者：
Estrada, Jesus G.;Williams, Wendy L.;Doyle, Abigail G.
我们先前报道了一种缺电子烯烃（EDO）配体Fro-DO的开发，其通过Ni催化的Csp（3）-Csp（3）与氮杂环丙烷交叉偶联促进季碳中心的产生。相比之下，电子和结构上相似的EDO配体如富马酸二甲酯和缺电子苯乙烯主要提供β-氢化物消除副反应性。只有少数催化剂体系已被鉴定为通过Ni催化的Csp（3）-Csp（3）交叉偶联促进季碳的形成。虽然Fro-DO在这方面代表了一种有前途的配体，但其上级性能的基础还没有得到很好的理解。在这里，我们描述了氮丙啶交叉偶联反应的详细机理研究和EDO配体在促进Csp（3）-Csp（3）键形成中的作用。该分析表明，交叉偶联通过具有Ni-II氮杂金属环丁烷催化剂静止状态的Ni-0/II循环进行。转换限制C-C还原消除发生从光谱可观察到的镍-II-二烷基中间体绑定到EDO。计算分析表明，Fro-DO通过降低LUMO加速周转限制还原消除。然而，在降低Csp（3）-Csp（3）还原消除障碍方面，其并不比富马酸二甲酯更有效。相反，Fro-DO的独特反应性源于其与Ni-II中间体有利结合的能力。自然键级二级微扰理论分析的催化相关的镍-II中间体表明，Fro-DO结合到镍-II通过一个额外的稳定的供体-受体之间的相互作用，其磺酰基和镍-II。设计新的配体来评估这一提议支持了这一模型，并导致了新的可调配体框架的开发。
We previously reported the development of an electron-deficient olefin (EDO) ligand, Fro-DO, that promotes the generation of quaternary carbon centers via Ni-catalyzed Csp(3)-Csp(3) cross-coupling with aziridines. By contrast, electronically and structurally similar EDO ligands such as dimethyl fumarate and electron-deficient styrenes afford primarily beta-hydride elimination side reactivity. Only a few catalyst systems have been identified that promote the formation of quaternary carbons via Ni-catalyzed Csp(3)-Csp(3) cross-coupling. Although Fro-DO represents a promising ligand in this regard, the basis for its superior performance is not well understood. Here we describe a detailed mechanistic study of the aziridine cross-coupling reaction and the role of EDO ligands in facilitating Csp(3)-Csp(3) bond formation. This analysis reveals that cross-coupling proceeds by a Ni-0/II cycle with a Ni-II azametallacyclobutane catalyst resting state. Turnover-limiting C-C reductive elimination occurs from a spectroscopically observable Ni-II-dialkyl intermediate bound to the EDO. Computational analysis shows that Fro-DO accelerates turnover limiting reductive elimination via LUMO lowering. However, it is no more effective than dimethyl fumarate at reducing the barrier to Csp(3)-Csp(3) reductive elimination. Instead, Fro-DO's unique reactivity arises from its ability to associate favorably to Ni-II intermediates. Natural bond order second-order perturbation theory analysis of the catalytically relevant Ni-II intermediate indicates that Fro-DO binds to Ni-II through an additional stabilizing donor-acceptor interaction between its sulfonyl group and Ni-II. Design of new ligands to evaluate this proposal supports this model and has led to the development of a new and tunable ligand framework.