有机人名反应|Buchwald–Hartwig Cross Coupling

人名反应

Buchwald–Hartwig Cross Coupling

Buchwald–Hartwig偶联反应最早可追溯至1983年，随后在在1994年由Buchwald^[1]和Hartwig^[2]建立并优化。过渡金属(钯)催化的芳基卤化物或假卤化物和一级或二级胺之间的交叉耦合，形成芳香胺。该反应在单体配体和螯合配体中表现出不同的反应机理。大致的催化循环是芳基卤代物氧化加成钯催化剂，然后胺加入复合物或者卤化物阴离子被碱从复合物中去除，最后通过还原消除得到产物，催化剂再生。钯催化剂也可用铜替换^[3]。

反应机理

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反应实例

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反应操作（ref.9）✦

An oven-dried resealable Schlenk tube was purged with argon and charged with Pd₂(dba)₃(0.005–0.025 mmol, 1–5 mol% Pd)，Ligand(0.015–0.075 mmol, 1.5–7.5mol%), and NaOt-Bu (1.4 mmol) [see Table 1 for amount of Pd and ligand used]. The tube was purged with argon, fitted with a rubber septum and then DME (0.5 mL–1.0 mL), the aryl bromide (1.0 mmol) and the amine (1.2 mmol) were added via syringe. The septum was removed, the tube was sealed with a teflon screw cap and the mixture was stirred at room temperature for 24 h. The reaction mixture was then diluted with ether (20 mL), filtered through celite and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel.

参考文献

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[1] A. S. Guram, S. L. Buchwald. Palladium-Catalyzed Aromatic Aminations with in situ Generated Aminostannanes. J. Am. Chem. Soc.1994, 116, 7901–7902.

[2] F. Paul, J. Patt, J. F. Hartwig. Palladium-Catalyzed Formation of Carbon-Nitrogen Bonds. Reaction Intermediates and Catalyst Improvements in The Hetero Cross-Coupling of Aryl Halides and Tin Amides. J. Am. Chem. Soc. 1994, 116, 5969–5970.

[3] F. Y. Kwong, A. Klapars, S. L. Buchwald. Copper-Catalyzed Coupling of Alkylamines and Aryl Iodides:  An Efficient System Even in an Air Atmosphere. Org. Lett. 2002, 4, 581–584.

[4] T. Taeufer, J. Pospech. Palladium-Catalyzed Synthesis of N,N-Dimethylanilines via Buchwald−Hartwig Amination of (Hetero)aryl Triflates. J. Org. Chem. 2020, 85, 7097−7111.

[5] D. W. Old, J. P. Wolfe, S. L. Buchwald. A Highly Active Catalyst for Palladium-Catalyzed Cross-Coupling Reactions:  Room-Temperature Suzuki Couplings and Amination of Unactivated Aryl Chlorides. J. Am. Chem. Soc. 1998, 120, 9722–9723.