Photoinduced, Copper-Catalyzed Enantioconvergent Alkylations of Anilines by Racemic Tertiary Electrophiles: Synthesis and Mechanism.
Photoinduced, Copper-Catalyzed Enantioconvergent Alkylations of Anilines by Racemic Tertiary Electrophiles: Synthesis and Mechanism.
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DOI：
10.1021/jacs.1c12749
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发表时间：
2022-03-16
影响因子：
15
通讯作者：
Fu, Gregory C.
中科院分区：
文献类型：
--
作者：
Cho, Hyungdo;Suematsu, Hidehiro;Oyala, Paul H.;Peters, Jonas C.;Fu, Gregory C.
过渡金属催化氮亲核试剂取代烷基亲电化合物已成为合成高级胺以及控制其立体化学的有效策略。在这里，我们报道了一种易于获得的手性铜催化剂(商业上可获得的组分)可以实现各种外消旋叔烷基亲电体与苯胺亲核剂的光诱导、对映体收敛偶联，从而在产物的全取代立体中心与良好的ee生成新的C-N键；虽然这种光诱导的铜催化偶联是在−78°C进行的，但在光和催化剂的作用下，即使加热到80°C，也几乎没有观察到C-N键的形成。人们借助一系列工具研究了这种新的催化对映体聚合取代过程的机理，包括建议的中间体的独立合成和反应活性研究，具有光物理和电子顺磁共振数据的光谱研究，以及密度泛函计算。这些研究导致了在所提出的催化循环中识别出三个铜基中间体，包括手性三配位形式的铜(II)-苯胺基(DFT分析表明其公式为铜(I)-苯胺基)络合物，该络合物充当持久自由基，与叔基有机自由基偶联，生成具有良好对映选择性的所需C-N键。
Transition-metal catalysis of substitution reactions of alkyl electrophiles by nitrogen nucleophiles is beginning to emerge as a powerful strategy for synthesizing higher-order amines, as well as controlling their stereochemistry. Herein, we report that a readily accessible chiral copper catalyst (commercially available components) can achieve the photoinduced, enantioconvergent coupling of a variety of racemic tertiary alkyl electrophiles with aniline nucleophiles to generate a new C–N bond with good ee at the fully substituted stereocenter of the product; whereas this photoinduced, copper-catalyzed coupling proceeds at −78 °C, in the a bsence of light and catalyst, virtually no C–N bond formation is observed even upon heating to 80 °C. The mechanism of this new catalytic enantioconvergent substitution process has been interrogated with the aid of a wide array of tools, including the independent synthesis of proposed intermediates and reactivity studies, spectroscopic investigations featuring photophysical and EPR data, and DFT calculations. These studies led to the identification of three copper-based intermediates in the proposed catalytic cycle, including a chiral three-coordinate formally copper(II)–anilido (DFT analysis points to its formulation as a copper(I)–anilidyl radical) complex that serves as a persistent radical that couples with a tertiary organic radical to generate the desired C–N bond with good enantioselectivity.
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影响因子：
23.5
作者：
Dow NW;Cabré A;MacMillan DWC
通讯作者：
MacMillan DWC
影响因子：
15
作者：
Bartoszewicz, Agnieszka;Matier, Carson D.;Fu, Gregory C.
通讯作者：
Fu, Gregory C.
影响因子：
64.8
作者：
Chen C;Peters JC;Fu GC
通讯作者：
Fu GC
影响因子：
2.1
作者：
Kouznetsov, Vladimir V.;Puerto Galvis, Carlos E.
通讯作者：
Puerto Galvis, Carlos E.
影响因子：
15
作者：
Mankad, Neal P.;Antholine, William E.;Peters, Jonas C.
通讯作者：
Peters, Jonas C.