Metal-Free Transformation of Phenols into Substituted Benzamides: A Highly Selective Radical 1,2-O→C Transposition in O-Aryl-N-phenylthiocarbamates
Metal-Free Transformation of Phenols into Substituted Benzamides: A Highly Selective Radical 1,2-O→C Transposition in O-Aryl-N-phenylthiocarbamates
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DOI：
10.1002/chem.201002303
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Alabugin, Igor V.
中科院分区：
文献类型：
--
作者：
Baroudi, Abdulkader;Flack, Phillip;Alabugin, Igor V.
利用酚类化合物中O±C键的反应性来生成苯甲酸衍生物的反应数量有限。最常见的是，这些转化是基于金属(Pd)催化的芳香族三氟化物的羰基化反应。[1]将苯酚转化为苯甲酸衍生物的一种简便的无金属方法将成为一个重要的合成进展，为这些过程提供了一个有用的替代方案。灵感来自于对O的观察！[2][2]我们实验室最近开发了一种简便的将苯酚转化为苯甲酸酯的方法。[3]这种转化是通过O-新叶基重排[5]/碎裂序列(方案1，ACHTUNGTRENNUNG[等式(2)])改变Barton-McCombie[4]反应的路线来设计的。尽管二芳基硫代碳酸酯的自由基转化提供了从好到高的芳基苯甲酸酯[式(2)]，但对于昂贵的苯酚来说，这可能是不切实际的，因为它需要相应起始材料的两个当量。由于不对称的二芳基硫代碳酸酯只表现出中等的选择性，因此采用不同的方法来选择O！为了扩大这一反应的范围，并充分利用这一潜在的非常有用的两步转化为苯甲酸衍生物的过程，C转位是必要的。O-烷基取代的硫代碳酸酯的重排导致众所周知的自由基断裂(结合在Barton-McCombie脱氧途径中)，而不形成重排产物(苯甲酸酯)。[3]相反，通过相同的过程对C+N键进行自由基断裂是低效的。例如，尽管α-氢的可逆自由基抽离很容易发生在胺中，但在这些条件下没有观察到C±N键的断裂。[6]我们对模型硫代氨基甲酸盐中C±N自由基断裂的计算研究估计，势垒约为29kcalmo1(方案2a)，[7]，比硫代碳酸盐中的O-新叶醇重排的势垒高5-7kcalmol？1。受到这些结果的鼓舞，我们用N-烷基部分取代了O-烷基取代基，以研究各自的硫代氨基甲酸酯是否会提供更具选择性的自由基重排(方案2b)。我们最初测试了O！N，N-二乙基-O-苯基硫代氨基甲酸酯中的C转位。不幸的是，即使在1358℃的苯中加热4小时后，该化合物对Et3SiH(2当量)和叔丁基过氧化氢(TOOT，1当量)仍然没有反应(方案3a；表1，条目1)。为了测试反应活性的缺乏是否是由于与相邻的氮孤对的超共轭相互作用使异构体自由基过度稳定所致，我们修改了-
There are a limited number of reactions that utilize the reactivity of the OÀC bond in phenols for the formation of benzoic acid derivatives. Most frequently, these transformations are based on metal (Pd)-catalyzed carbonylation of aromatic triflates.[1] An expedient metal-free approach for the conversion of phenols into benzoic acid derivatives would become a significant synthetic advance by providing a useful alternative to these processes. Inspired by the observation of O! C radical transposition triggered by the Bergman cyclization of enediynes (Scheme 1,[Eq.(1)]),[2] our lab has recently developed a convenient procedure for the conversion of phenols into benzoate esters.[3] This transformation was designed through rerouting the Barton–McCombie [4] reaction via an O-neophyl rearrangement [5]/fragmentation sequence (Scheme 1, ACHTUNGTRENNUNG [Eq.(2)]). Although the radical transformation of diaryl thiocarbonates affords aryl benzoates in good to high yields [Eq.(2)], it can be unpractical for expensive phenols because it requires two equivalents of the corresponding starting material. As unsymmetrical diaryl thiocarbonates show only moderate selectivity, a different approach to selective O! C transposition has been necessary for broadening the scope of this reaction and taking the full advantage of this potentially very useful two-step transformation of phenols into benzoic acid derivatives.The rearrangement of O-alkyl-substituted thiocarbonates leads to the well-known radical fragmentation (incorporated in the Barton–McCombie deoxygenation pathway) without the formation of rearrangement product (benzoate ester).[3] In contrast, radical fragmentation of CÀN bonds through the same process is inefficient. For example, although reversible radical abstraction of the α-hydrogen readily occurs in amines, no scission of CÀN bonds is observed under these conditions.[6] Our computational study on the CÀN radical fragmentation in a model thiocarbamate estimates a barrier of about 29 kcalmolÀ1 (Scheme 2 a),[7] which is 5–7 kcalmolÀ1 higher than that of the O-neophyl rearrangement in thiocarbonates. Encouraged by these results, we replaced the O-alkyl substituent with an N-alkyl moiety to investigate whether respective thiocarbamates will afford a more selective radical rearrangement (Scheme 2b). We initially tested the viability of the O! C transposition in N, N-diethyl-O-phenyl thiocarbamate. Unfortunately, this compound remained unreactive towards Et3SiH (2 equiv) and tert-butyl peroxide (TOOT, 1 equiv) even after heating for 4 h at 1358C in benzene (Scheme 3a; Table 1, entry 1). To test whether the lack of reactivity is due to the excessive stabilization of the anomeric radical by the hyperconjugative interaction with the adjacent nitrogen lone pair, we modi-