铜催化苯硼酸与苯并呋咱-1-氧化物的胺化反应（英文）

发布时间：2018-08-25 08:17

【摘要】：C-N键普遍存在于药物和有机功能分子中,传统构建C-N键的方法包括Goldberg反应、Buchwald-Hartwig偶联、Chan-Lam偶联和C-H键活化胺化.虽然这些方法都可以高效构建C-N键,但它们需要使用官能化的芳基底物、官能化的胺化试剂或在氧化条件下进行.理想的胺化反应应在氧化还原中性条件下进行,更为理想的则是在引入氨基的同时引入另外一个官能团.实现这个目标最直接的策略就是使用氮杂环,通过N-E(E=N或O)键的断裂,N原子和E原子可同时被引入.最近我们课题组利用氨茴内酐和氮杂苯并降冰片烯的C-H键活化反应成功实现了这种双官能团化.尽管该法很有吸引力,但是要通过氮杂环的断裂实现双官能团化,需要发生非张力环的开环,这在热力学上是非常不利的.苯并呋咱-1-氧化物可以开环得到邻二硝基苯中间体.基于对胺化反应的兴趣,我们推测苯并呋咱1-氧化物可以作为一个胺化试剂实现苯硼酸的胺化.尽管亚硝基苯对芳基硼酸进行简单的胺化已经被报道,但需要化学计量的铜盐,或是引入还原剂.因此本文报道铜催化的苯硼酸的胺化反应,该反应以苯并呋咱1-氧化物为胺化试剂,在温和及氧化还原中性条件下成功实现了双官能团化.本文共完成了31个不同官能团取代的硝基苯胺骨架结构的合成,反应均以中等到良好的收率得到目标产物,最高收率可达99%.为了增加反应的实用性,我们还进行了放大实验,实验表明,当苯并呋咱-1-氧化物的量由0.2 mmol放大至4 mmol时,反应仍能以较高的收率得到目标产物.此外,目标产物通过进一步的衍生化反应还可方便地转化为其他杂环类化合物.例如,在PPh_3作用下,通过还原环化作用可生成吩嗪.在钯催化下可发生分子内碳氢键氧化反应得到咔唑类化合物.通过还原及重氮化反应还可方便地转化为苯并三唑.总之,我们以苯并呋咱-1-氧化物为胺化试剂,在铜催化下成功实现了苯硼酸的胺化反应,合成了一系列双官能团化产物.该催化体系反应条件温和,底物适用范围广,对各种官能团具有很好的兼容性.
[Abstract]:C-N bonds are commonly found in drugs and organic functional molecules. The traditional methods for the construction of C-N bonds include Goldberg reaction, Buchwald-Hartwig coupling, Chan-Lam coupling and activated amination of C-H bonds. Although these methods can efficiently construct C-N bonds, they require the use of functionalized aryl substrates, functionalized amination reagents or oxidation conditions. The ideal amination reaction should be carried out under the redox neutral condition, and the more ideal is the introduction of another functional group at the same time as the introduction of amino groups. The most direct strategy to achieve this goal is the use of nitrogen heterocycles, which can be introduced simultaneously through the breaking N and E atoms of N-E (EN or O) bonds. Recently, this bifunctional group was successfully realized by C-H bond activation of aniline and azobenzene. Although the method is very attractive, it is difficult to realize the bifunctional group formation by breaking the nitrogen heterocyclic ring, which is very disadvantageous in thermodynamics. Benzofurazan-1-oxide can open the ring to obtain the intermediate of o-dinitrobenzene. Based on the interest in amination, we speculate that benzofurazan 1-oxide can be used as an amination reagent for the amination of phenylboric acid. Although the simple amination of nitrobenzene for aryl boric acid has been reported, stoichiometric copper salts or reductants are required. In this paper, the copper-catalyzed amination of phenylboric acid was reported. The difunctional group reaction was successfully achieved under mild and redox neutral conditions using benzofurazan 1-oxide as the amination reagent. In this paper, 31 different functional groups substituted nitrophenylamine skeleton structure were synthesized. The target product was obtained in medium to good yield, and the highest yield was up to 99%. In order to increase the practicability of the reaction, an amplification experiment was carried out. It was shown that when the amount of benzofurazan-1-oxide was amplified from 0.2 mmol to 4 mmol, the target product could still be obtained in high yield. In addition, the target product can be easily transformed into other heterocyclic compounds by further derivatization. For example, phenazine can be produced by reducing cyclization under the action of PPh_3. Under the catalysis of palladium, carbazole compounds can be synthesized by intramolecular hydrocarbon bond oxidation. Through reduction and diazotization, it can also be easily converted to benzotriazole. In conclusion, benzofurazan-1-oxide was used as an amination reagent, and a series of difunctional group products were synthesized by copper-catalyzed amination of phenylboric acid. The reaction conditions of the catalytic system are mild, and the substrate has a wide range of application, and it has good compatibility with various functional groups.
【作者单位】：河南师范大学化学化工学院河南省精细化工绿色生产协同创新中心河南省有机功能分子和药物创新重点实验室;中国科学院大连化学物理研究所;
【基金】：supported by the National Natural Science Foundation of China(21525208 and 21472186) Research Fund from Henan Normal University(5101034011009)~~
【分类号】：O621.251

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