光催化氧化还原体系中硝酮与芳香叔胺的自由基偶联反应

doi:10.6023/A19040150

摘要/Abstract

通过氮α-位碳自由基构造氮α-位碳-碳键是合成含氮有机化合物的重要方法. 近期, 利用可见光催化氧化芳香叔胺—氮α-位去质子化形成氮α-位碳自由基的原理发展了一系列新颖的自由基加成(偶联)反应, 成为氮α-位碳自由基化学发展的重要方向. 本文应用Ir-催化剂, 实现了光催化氧化还原体系中硝酮与芳香叔胺的自由基偶联反应, 高效地合成β-氨基羟胺化合物. 该反应条件温和、操作简单, 具有较高的原子经济性, 且对于各种链状、环状以及手性硝酮都具有良好的适用性, 产物可方便地转化为重要的邻二胺化合物.

关键词: 氮α-位碳自由基, 光催化氧化还原, 偶联反应, 芳香叔胺, 硝酮

Carbon-carbon bond formation at α-amino carbon based on α-aminoalkyl radicals is an essential transformation in the synthesis of nitrogen-containing compounds. Recently, some novel photoredox catalytic protocols for this goal have been developed, in which α-aminoalkyl radicals were generated from a sequential oxidation/α-deprotonation of aromatic tertiary amines. Inspired by these studies and based on our previous works, we have developed the cross-coupling reaction of nitrones with aromatic tertiary amines via visible light photoredox catalysis. This method features a radical addition of α-aminoalkyl radicals to nitrones with advantages of simple operation, mild conditions, atom economy, a broad scope of nitrone substrates; and allows for an easy access to β-amino hydroxylamines, which could be readily converted into vicinal diamines. Compared with the UV-excited organophotosensitizer-promoted coupling reaction of nitrones with tertiary amines, visible light is a more safe and convenient light source, the photo-excited electron transfer (PET) by 1 mol% of Ir-photocatalyst is more efficient. In addition, nitrones exclusively server as excellent radical acceptors thus with a broader range of structures. A general procedure of this coupling reaction is as follows: To a 25 mL Schlenk tube equipped with a magnetic stir bar were added a nitrone (0.30 mmol), a tertiary amine (0.90 mmol), Ir(ppy)₂(dtbbpy)PF₆ (0.003 mmol, 1.0 mol%) and K₂HPO₄ (0.06 mmol, 20 mol%). After being evacuated and backfilled with argon for three times, DMSO (3 mL) was added to the tube. Then the tube was placed approximately 7 cm away from a 12 W blue LEDs, and the reaction mixture was stirred at r.t. under an argon atmosphere for 24 h. The reaction was quenched with saturated aqueous NaHCO₃ (25 mL), and the mixture was extracted with dichloromethane (DCM, 20 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to afford the desired cross-coupling product β-amino hydroxylamine.

Key words: α-aminoalkyl radicals, photoredox catalysis, coupling reaction, aromatic tertiary amine, nitrone

引用此文

刘玉成, 郑啸, 黄培强. 光催化氧化还原体系中硝酮与芳香叔胺的自由基偶联反应[J]. 化学学报, 2019, 77(9): 850-855.

Liu, Yu-Cheng, Zheng, Xiao, Huang, Pei-Qiang. Photoredox Catalysis for the Coupling Reaction of Nitrones with Aromatic Tertiary Amines[J]. Acta Chimica Sinica, 2019, 77(9): 850-855.

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图/表 7

图式1. 可见光催化氧化还原体系中硝酮与芳香叔胺的自由基偶联反应设计

Scheme 1. The design of cross-coupling of nitrones with aromatic tertiary amines via visible light photoredox catalysis

Entry	Variation from standard condition	Yield/%
1	Ru(bpy)₃(PF₆)₂/Cs₂CO₃	14
2		84
3	No Photocatalyst	0
4	No LEDs	0
5	No K₂HPO₄	0

表1. 对照实验

Table 1. Control experiments

表2. 硝酮与N,N-二甲基苯胺2a的交叉偶联反应

Table 2. Cross-coupling of nitrones with N,N-dimethylaniline 2a

表3. 硝酮1a与芳香叔胺的交叉偶联反应

Table 3. Cross-coupling of nitrone 1a with aromatic tertiary amines

图式2. 氮α-位碳自由基的捕获实验

Scheme 2. The trapping experiment of α-aminoalkyl radical

图式3. 芳香叔胺的回收实验

Scheme 3. Recovery of tertiary amine at the end of the reaction

图式4. 推测的反应机理

Scheme 4. The proposed mechanism

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