镍或铜催化C（sp2）-C（sp3）键构建研究

发布时间：2018-03-12 14:40

本文选题：C(sp~2)-C(sp~3)键　切入点：开环反应　出处：《中国科学技术大学》2017年博士论文　论文类型：学位论文

【摘要】：过渡金属催化C-C键交叉偶联反应是合成化学中的强有力工具。过去的几十年,大量的过渡金属催化交叉偶联反应新方法被人们报道,并广泛用于合成复杂的天然分子中。相比于其他类型的C-C键构建反应,如C(sp~2)-C(sp~2)键,C(sp~3)-C(sp~3)键,C(sp~2)-C(sp~3)键构建反应由于其在合成中有着广泛的应用,其新合成方法研究一直是人们关注的重点。相比于钯、铱等过渡金属,铜和镍金属在经济上便宜、毒性低,近来这两种金属催化C(sp~2)-C(sp~3)键交叉偶联反应一直是人们研究的重点。本文在第一章先简要陈述了铜和镍金属催化C(sp~2)-C(sp~3)键交叉偶联反应。有机金属试剂参与交叉偶联反应主要包括如下试剂:有机锌试剂,格氏试剂,硼试剂,锆试剂、锡试剂和硅试剂等。而传统的亲电试剂主要是卤化物和磺酸酯类化合物。近来环氧及吖啶与C(sp~2)负试剂(锌试剂、硼试剂)的开环交叉偶联构建C(sp~2)-C(sp~3)键的反应引起了人们很大的兴趣,相比于传统的卤化物和磺酸酯类卤化物,环氧和吖啶发生开环偶联反应后还可以引入烷基醇和烷基胺,这是其作为合成子的优势所在。同时,通过炔烃与烷基亲电试剂的氢-烷基化构建C(sp~2)-C(sp~3)键的反应最近也受到人们追捧,其优点是该类反应不需要使用金属试剂而且炔烃相对于金属试剂来说易得、对空气和水分不敏感、反应条件温和、官能团兼容性好。同时还有控制炔烃加成反应区域选择性的潜能,近而可以合成多种取代类型的烯烃化合物。针对目前环氧开环反应大多使用比较强的C(sp~2)类型亲核试剂,如金属锂试剂,格氏试剂。其缺点是反应官能团兼容性差、原料来源受限。硼试剂相比于这些强亲核试剂,更加稳定易得,官能团兼容性好。在第二章中,我们报道了 CuI催化下环氧与芳基硼的开环反应。这是首例Cu催化芳基硼与环氧的开环反应。反应不仅对于普通单取代环氧是合适的底物,对于1,1-二取代环氧底物也适用。芳基环氧化合物,通过微调反应条件也能得到理想的产率。相比于格氏试剂和锂试剂的开环反应,反应有着良好的官能团兼容性。烯烃是一类重要的有机分子,广泛存在于材料、医药行业中。传统的合成方法,如消除反应、还原反应、缩合反应、Julia-Kocienski烯化反应等依然在现代合成中被使用。最近,炔烃与sp~3亲电试剂的分子间氢-烷基化构建C(sp~2)-C(sp~3)键的反应受到人们重视。这类反应的优点是原料易得、并且有控制反应区域和立体选择性的潜能。然而炔烃和非活化C(sp~3)类型亲电试剂之间的交叉偶联反应的例子是非常少的。在第三章中,我们选择末端炔烃和烷基碘为偶联底物,报道了第一例末端炔烃与C(sp~3)类型亲电试剂的马氏选择性氢-烷基化反应。反应不需要使用敏感的金属试剂,操作简单,原料易得,反应条件温和,选择性高,官能团兼容性好。为1,1-二取代烯烃提供了高效的合成策略。
[Abstract]:Transition metal-catalyzed C-C bond cross-coupling is a powerful tool in synthetic chemistry. In the past few decades, a large number of new methods of transition metal-catalyzed cross-coupling have been reported. And is widely used in the synthesis of complex natural molecules. Compared with other types of C-C bond construction reactions, such as Cnsp ~ (2) C ~ (+) -C ~ ((+)) / C ~ ((1)) / C ~ ((1)) / C ~ ((1)) / C ~ ((2)) / C ~ ((1)) / C ~ (2) / C ~ ((1)) / C / C / C ~ (3) / C ~ (2), Compared with transition metals such as palladium and iridium, copper and nickel metals are economically inexpensive and less toxic. Recently, the cross-coupling reaction of these two metals catalyzed by Cnsp ~ (2) -C ~ ((1)) has been the focus of research. In the first chapter, the cross-coupling reaction between copper and nickel (Cspn2) -C _ (sp) ~ (3) is briefly described. Organometallic reagents take part in the cross-coupling reaction. Mainly include the following reagents: organic zinc reagent, Grignard reagents, boron reagents, zirconium reagents, tin reagents and silicon reagents, etc. Traditional electrophilic reagents are mainly halides and sulfonic esters. The reaction of ring opening cross-coupling of boron reagent to construct C _ (sp ~ (2)) C _ (P _ (2)) bond has aroused great interest. Compared with traditional halides and sulfonic esters, alkyl alcohols and alkyl amines can also be introduced into epoxy and acridine after ring-opening coupling reaction between epoxy and acridine. At the same time, the reaction of alkynes and alkyl electrophilic reagents to form the C _ SSP _ 2C _ N _ (3) bond has been popular recently, and this is its advantage as a synthesizer, and the reaction of alkynes and alkyl electrophilic reagents is also very popular in recent years. The advantage is that such reactions do not require the use of metal reagents and alkynes are readily available relative to metal reagents, are insensitive to air and water, and have mild reaction conditions. Functional groups have good compatibility. At the same time, there is the potential to control the region selectivity of alkynes addition reaction, and can synthesize a variety of alkene compounds. For example, lithium metal reagents and Grignard reagents have the disadvantages of poor compatibility of functional groups and limited source of raw materials. Compared with these strong nucleophilic reagents, boron reagents are more stable and easy to obtain. We report the ring-opening reaction between epoxy resin and aryl boron catalyzed by CuI. This is the first case of cu catalyzed ring opening reaction between aryl boron and epoxy resin. The ideal yield of aryl epoxy compounds can also be obtained by fine-tuning the reaction conditions. Compared with the ring opening reaction of Grignard reagent and lithium reagent, Olefin is an important class of organic molecules, which is widely used in the field of materials and medicine. Traditional synthesis methods, such as elimination reaction, reduction reaction, Condensation reactions such as Julia-Kocienski alkenylation are still used in modern synthesis. Recently, the hydrogen-alkylation of alkynes with sp~3 electrophilic reagents has been paid attention to. However, there are very few examples of cross-coupling reactions between alkynes and unactivated CSP3 type electrophilic reagents. In Chapter 3, we select terminal alkynes and alkyl iodine as coupling substrates. The first case of selective hydrogen-alkylation of terminal alkynes with Cnspsp3) type electrophilic reagents is reported. The reaction does not require the use of sensitive metal reagents, the operation is simple, the raw materials are easy to be obtained, the reaction conditions are mild and the selectivity is high. The functional groups have good compatibility. It provides an efficient synthesis strategy for 1C 1-disubstituted olefin.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

【相似文献】