摘要/Abstract

发展了一种高效的通过钯催化导向碳-氢键活化的策略在苯环上引入酯基官能团的方法.草酸单乙酯钾盐在过硫酸钾和碳酸银的协同作用下脱羧生成酯基自由基，然后酯基自由基加成到钯环上，最后经过还原消除的过程实现了2-苯氧基吡啶苯环的邻位酯基化.该反应为合成一系列水杨酸乙酯衍生物提供了一种切实有效的途径.
关键词: 钯催化, 碳-氢键活化, 2-苯氧基吡啶, 脱羧, 酯基化
Transition metal-catalyzed C—H activation has attracted extensive attention because of its excellent functional group tolerance and high efficiency. Among them, palladium-catalyzed reactions exhibit versatile catalytic cycles and have mild conditions compared to others. Therefore, the palladium-catalyzed C—H activation has been employed broadly as a practical strategy in synthetic chemistry during the past decade. Since the first example of palladium-catalyzed decarboxylative C—H acylation using α-oxocarboxylic acids was reported in 2008, a lot of substrates have been employed to synthesize acylated products due to the easily available α-oxocarboxylic acids as well as the importance of acylation. However, the transition metal-catalyzed C—H esterification via decarbonylation is still limited. Our group previously developed the first directed C—H esterification of methyl ketoximes and 2-phenylpyridines by using potassium oxalate monoester as the decarboxylative reagent. Encouraged by this impressive result as well as the importance of salicylate derivatives in drug discovery, herein we disclose the efficient palladium-catalyzed decarboxylative esterification of 2-aryloxpyridines. This reaction proceeds smoothly with potassium oxalate monoester, affording the desired products in moderate to good yields (50%~82%). Compared to our previous work, the electron-donating pyridinyloxy (PyO) group as the directing group and six-membered metallocycle intermediate dramatically enhance the practicability and substrate tolerance of the present method. In addition, one of the products has been chosen as the model compound to deprotect the directing group to get the valuable salicylate derivative. The present method not only provides an efficient and convenient protocol for the synthesis of ethyl salicylate derivatives, but also enriches the diversity of Pd(Ⅱ)/Pd(IV) catalytic reactions. A general procedure for the esterification of 2-aryloxypyridines 1 with potassium oxalate monoester 2 is as following:a mixture of 1 (0.5 mmol), Pd(OAc)₂ (10 mol%), K₂S₂O₈ (1.0 mmol), Ag₂CO₃ (1.0 mmol), 2 (1.0 mmol), D-CSA (0.125 mmol), and 1,4-dioxane (2.5 mL) in a 25 mL tube was heated at 80℃ for a suitable time. The reaction mixture was cooled to room temperature, and concentrated in vacuo. Purification of the residue by column chromatography on silica gel with petroleum ether and ethyl acetate as the eluent provided the desired product 3.
Key words: palladium catalysis, C—H activation, 2-aryloxypyridine, decarboxylation, esterification


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