光/镍协同催化不对称C-N偶联反应合成轴手性联芳基芳胺★

doi:10.6023/A26070256

摘要/Abstract

轴手性杂联芳基芳胺不仅是天然产物和生物活性分子中的重要骨架, 更因卓越的催化性能被广泛用作手性配体或有机催化剂, 其高效不对称合成备受关注. 光/镍协同催化可在温和条件下实现多样性C(sp²)-杂原子键偶联, 然而其对映选择性版本至今鲜有报道, 是该领域亟待突破的难题. 本文发展了一种光/镍协同催化体系, 以简单芳胺为亲核试剂, 实现了其与外消旋杂联芳基三氟甲磺酸酯的阻转选择性C(sp²)-N键偶联. 反应最高能以98%的收率和86%的对映选择性获得目标产物. 该体系对各类取代苯胺、稠环芳胺、杂环芳胺以及杂联芳基三氟甲磺酸酯均表现出良好的兼容性. 机理实验表明反应经历单电子转移途径而非能量转移机制, 在此基础上我们提出了Ni(0/II/II/III/I/0)催化循环机理. 本研究为光/镍协同催化不对称C(sp²)-N偶联提供了新策略, 开辟了轴手性联芳基芳胺不对称合成的新途径.

关键词: 不对称C(sp²)-N偶联, 光/镍协同催化, (杂)联芳基阻转异构体, 轴手性, 不对称催化

Axially chiral heterobiaryl anilines are privileged scaffolds widely embedded in natural products and bioactive molecules, and they serve as highly efficient chiral ligands or organocatalysts owing to their outstanding catalytic performance. As a result, the development of efficient asymmetric synthetic methods for these architectures has attracted intense attention. Photoredox/nickel dual catalysis has emerged as a versatile and mild platform for the construction of diverse C(sp²)-heteroatom bonds; however, its enantioselective variant remains extremely rare. Herein, we develop a single-electron-transfer (SET)-based photoredox/nickel dual catalytic system that accomplishes atroposelective C(sp²)-N bond formation between readily available arylamines and racemic heterobiaryl triflates. After systematic optimization of the reaction parameters, the desired axially chiral products were obtained in up to 98% yield and 86% enantiomeric excess (ee). The general procedure for this atroposelective C-N coupling is as follows: inside a nitrogen-filled glovebox, NiBr₂(DME) (10 mol%) and chiral ligand (12 mol%) were combined with photocatalyst (2 mol%) in anhydrous toluene (3.0 mL) and stirred at room temperature for 30 min. Subsequently, racemic heterobiaryl triflates (0.1 mmol, 1.0 equiv.), arylamines (1.5 equiv.), N-tert-butylisopropylamine (1.5 equiv.), and ethyl acetate (3.0 mL) were added. The vial was sealed, brought out of the glovebox, and stirred under irradiation with 45 W blue LEDs at 0 ^oC for 12 h. After completion of the reaction, the mixture was concentrated in vacuo and purified by silica gel chromatography to afford the pure product. The substrate scope proved to be broad: a range of substituted anilines, heterocyclic arylamines, and structurally diverse heterobiaryl triflates were well tolerated. Mechanistic experiments demonstrated that the reaction operates through a SET pathway rather than an energy-transfer mechanism. This work not only provides a new strategy for photoredox/nickel dual-catalyzed asymmetric C(sp²)-N coupling but also opens an avenue for the enantioselective synthesis of axially chiral biaryl anilines.

Key words: Asymmetric C(sp²)-N bond coupling, Photoredox/Ni cocatalysis, (Hetero)Biaryl atropisomer, Axial chirality, Asymmetric catalysis

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吴明轩, 吴雨馨, 张洪浩, 陈群, 石枫. 光/镍协同催化不对称C-N偶联反应合成轴手性联芳基芳胺^★[J]. 化学学报, doi: 10.6023/A26070256.

Wu Ming-Xuan, Wu Yu-Xin, Zhang Hong-Hao, Chen Qun, Shi Feng. Photoredox/Nickel-Cocatalyzed Asymmetric C-N Couplings for Atroposelective Synthesis of Biaryl Anilines[J]. Acta Chimica Sinica, doi: 10.6023/A26070256.

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