碳氢键选择性官能团化反应方法研究——卤代芳烃和磷中心手性化合物的合成
文献类型：学位论文
| 作者 | 杜志军 |
| 学位类别 | 博士 |
| 答辩日期 | 2015-05 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 中国科学院长春应用化学研究所 |
| 导师 | 高连勋 ; 林英杰 ; 韩福社 |
| 关键词 | 卤代 选择性 去对称C－H芳基化 磷手性 |
| 中文摘要 | 芳基卤代物是一类非常重要的化工原料及有机合成中间体，也是很多天然产物和合成药的重要结构单元。芳基卤代物传统制备方法有一定局限性——区域选择性差，反应条件苛刻和底物范围有限。过渡金属催化C－H键直接卤代对传统卤代方法是一个很好补充。作为一种廉价金属，铜催化直接C－H键卤代引起了人们重视。然而，铜催化卤代反应的一个共同缺点是单、双卤代选择性差。另外，磷中心手性化合物手性控制更接近催化中心而显示了立体选择性的控制优势。但是，由于缺乏有效合成方法，它们的应用受到限制。特别要强调的是，一些有潜在应用的磷中心手性化合物，如磷中心手性布朗斯特酸，还不能通过目前的方法获得。本论文通过直接C－H键官能团化，高选择性合成了单、双卤代芳烃和高对映选择性合成了磷中心手性次膦酰胺。 首先，本论文实现了铜促进芳基C－H直接卤代。通过使用易得羧酸和N-卤代丁二酰亚胺（NXS, X = Br, Cl）原位生成高效卤代试剂——Acyl hypohalites，结合溶剂的合适搭配，高收率、高选择性地获得了单卤代和双卤代产物。 其次，发现含有非配位性阴离子的铜盐CuBF4(CH3CN)4能够改善催化卤代活性，用5 mol% of CuBF4(CH3CN)4可高收率获得卤代产物。因此，反应使用廉价铜催化剂和原位生成Acyl hypohalites作为卤代试剂的新策略，为实际应用提供了优势。 最后，首次通过去对称C－H官能化策略，实现了钯催化二芳基次膦酰胺与芳基硼酸频那醇酯偶联，合成了磷中心手性次膦酰胺。此方法能够高效合成磷中心手性化合物——偶联最高收率达到74％，最高ee值达到98％；此方法对于克级规模反应同样有效；为合成磷中心手性布朗斯特酸开辟了一条途径。另外，产物磷中心手性次膦酰胺可方便灵活地转化为各种磷中心手性化合物，并保持优异的对映选择性，为多样性合成其它磷中心手性化合物提供了一条新途径。 关键词：铜；卤代；选择性的；钯；去对称C–H芳基化；磷手性 |
| 英文摘要 | Aryl halides are a kind of extremely valuable compounds used in chemical industry and in organic synthesis. They are also important structure motifs in many natural products and manufactured drugs. Classical methods for the synthesis of aryl halides have suffered from some notable disadvantages, such as low regioselectivity, harsh conditions, and limited reaction substrates. As a complementary strategy, the transition-metal-catalyzed direct C－H bond halogenation has appeared to be a new and efficient option for the synthesis of aryl halides. In particular, inexpensive Cu catalyst for C－H bond halogenation is very attractive. However, selective mono- and di-halogenation was problematic for Cu-catalyzed halogenation. On the other hand, although P-stereogenic compounds have shown prominent chiral induction stemming from chirality proximate to the catalytic center, their wide application has been severely restricted because of the lack of efficient synthetic methods. More to the point, some types of potentially useful P-stereogenic compounds, such as P-chiral Br?nsted acid, are still inaccessible via conventional approaches for their preparation. This dissertation presents the protocols for highly selective halogenations and highly enantioselective synthesis of P-stereogenic phosphinamides via direct C－H bond functionalization. First, a protocol for the copper-mediated direct aryl C－H halogenation is presented. Highly selective mono- and di-halogenation are avhieved by using acyl hypohalites generated in situ from the readily available carboxylic acid and N-halosuccinimides (NXS, X = Br and Cl) as powerful halogenating reagents. The correct choice of carboxylic acid additives and solvents is essential for both high yield and selectivity. Second, catalytic acitivity for aryl C－H halogenation was significantly improved through using CuBF4(CH3CN)4 with non-coordinating anion. The halogenated products were obtained in high yield only using 5 mol% of CuBF4(CH3CN)4. Consequently, the use of inexpensive Cu catalyst and the new strategy for the in situ generation of acyl hypohalite as halogenating reagents offers advantages for practical application. Finally, the enantioselective synthesis of P-stereogenic phosphinamides has been achieved through Pd-catalyzed desymmetric ortho C－H arylation of diarylphosphinamides with arylboronic pinacol esters. A broad variety of P-stereogenic compounds was efficiently synthesized: in up to 74% yield and 98% ee; The efficiency was further demonstrated by gram scale syntheses; The protocol should open an unprecedented avenue for the synthesis of P-stereogenic Br?nsted acids; Moreover, the flexible conversion of the P-stereogenic phosphinamides into various types of P-stereogenic phosphorus derivatives was also elaborated, and the excellent enantioselectivity was kept, which provides a novel approach to versatile synthesis of P-stereogenic compounds. Key words: Copper; Halogenation; Selective; Palladium; Desymmetric C–H Arylation; P-Stereogenic. |
| 语种 | 中文 |
| 公开日期 | 2016-05-03 |
| 源URL | [http://ir.ciac.jl.cn/handle/322003/64483]  |
| 专题 | 长春应用化学研究所_长春应用化学研究所知识产出_学位论文 |
| 推荐引用方式 GB/T 7714 | 杜志军. 碳氢键选择性官能团化反应方法研究——卤代芳烃和磷中心手性化合物的合成[D]. 中国科学院长春应用化学研究所. 中国科学院研究生院. 2015. |
入库方式： OAI收割
来源：长春应用化学研究所
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