The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi, Jiangsu Province, China.
Dalton Trans. 2012 Dec 7;41(45):13832-40. doi: 10.1039/c2dt31500a. Epub 2012 Aug 28.
A systematic theoretical study on reaction mechanisms for copper(I)-catalyzed C-O coupling of phenols with aryl bromides is reported herein. Through evaluation of the relative concentrations of possible copper species in reaction solution and reactivity study of these copper species with aryl halides in the context of several commonly proposed mechanisms for copper(I)-catalyzed Ullmann reactions, we propose that the active copper catalyst should be a neutral (L)Cu(I)-OAr (L denotes an ancillary ligand; OAr denotes an aryloxide ligand) species in nonpolar solvent and Cu(OAr)(2)(-) anion in highly polar solvent. In the reaction solution, these two kinds of copper species should be in equilibrium, the direction of which is highly dependent on the polarity of the solvent. For both kinds of copper species, a halogen atom transfer mechanism is favored where an initial halogen atom transfer from phenyl bromide to the Cu(I) center occurs, resulting in the formation of Cu(II)(OAr)(Br) and a phenyl radical. Subsequent rapid attack of this phenyl radical to the aryloxide ligand bound to copper(II) would yield the coupling product and Cu(I)(Br) species, which can be readily converted to the active Cu(I)-OAr species in the presence of phenols and base. Other mechanisms such as oxidative addition, single electron transfer and σ-bond metathesis mechanisms all possess activation barriers which are too high, rendering them kinetically unfavorable. Electronic effects on phenol rings reveal that electron-donating substituents accelerate the coupling of (phen)Cu(I)(OAr) with aryl halides whereas electron-withdrawing substituents lead to much higher activation barriers, which is consistent with experimental findings and thus lends further support for such a halogen atom transfer mechanism. In view of the widely accepted oxidative addition/reductive elimination mechanism for analogous copper(I)-catalyzed coupling of N-nucleophiles with aryl halides, our results here highlight that the reaction mechanism of copper(I)-catalyzed Ullmann reactions is highly dependent on the nature of the nucleophile and different kinds of nucleophiles can be involved in different mechanisms.
本文对铜（I）催化酚与芳基溴的 C-O 偶联反应机理进行了系统的理论研究。通过评估反应溶液中可能的铜物种的相对浓度，并在几种常见的铜（I）催化 Ullmann 反应机理的背景下研究这些铜物种与芳基卤化物的反应性，我们提出活性铜催化剂在非极性溶剂中应为中性（L）Cu（I）-OAr（L 表示辅助配体；OAr 表示芳氧基配体）物种，在高极性溶剂中应为 Cu（OAr）（2）（-）阴离子。在反应溶液中，这两种铜物种应该处于平衡状态，其方向高度依赖于溶剂的极性。对于这两种铜物种，都有利于卤原子转移机理，其中苯基溴中的初始卤原子转移到 Cu（I）中心发生，导致形成 Cu（II）（OAr）（Br）和苯基自由基。随后，该苯基自由基迅速进攻与铜（II）配位的芳氧基配体，生成偶联产物和 Cu（I）（Br）物种，在酚和碱的存在下，这些物种可以很容易地转化为活性 Cu（I）-OAr 物种。其他机理，如氧化加成、单电子转移和 σ-键复分解机理，都具有过高的活化能垒，因此在动力学上是不利的。对酚环的电子效应表明，供电子取代基加速（phen）Cu（I）（OAr）与芳基卤化物的偶联，而吸电子取代基导致更高的活化能垒，这与实验结果一致，因此进一步支持这种卤原子转移机理。鉴于类似的铜（I）催化 N-亲核试剂与芳基卤化物偶联反应中广泛接受的氧化加成/还原消除机理，我们的结果突出表明，铜（I）催化 Ullmann 反应的反应机理高度依赖于亲核试剂的性质，不同种类的亲核试剂可以参与不同的机理。
