《药物合成反应》实验教学内容改革与实践

探索将不同类型重排反应引入到药物合成反应实验教学内容中,本文以乙酸苯酯为起始原料合成扑热息痛为例,过程涉及Fries重排、肟化、Beckmann重排等多个单元反应,可加深学生对重排反应机理的理解,有利于学生在实验过程中培养绿色合成意识,是对药物合成反应实验教学内容改革的有益探索。     

2-烯丙基-4-羟基-2-环戊烯酮的改进合成

2-烯丙基-4-羟基-2-环戊烯酮是合成前列腺素4-硫代-PGI1的关键中间体,具有重要的生理活性.采用改进方法以糠醛为原料经格氏反应和重排反应两步合成了2-烯丙基-4-羟基-2-环戊烯酮,并考察了酸催化剂种类、反应溶剂、酸含量和反应温度对重排反应的影响.结果表明,多聚磷酸具有最佳的催化性能,在100 ℃、n(多聚磷酸)/n(醇)=0.2的反应条件下,重排反应收率为79%,纯度为99.2%.两步反应的总收率为64%.     

法沃尔斯基重排应用研究

法沃尔斯基重排反应在光学活性的合成反应、较新的手性合成方法、高立方烷与新型的笼系化合物合成和一些重排合成反应中，一直都有着较为显著的应用。近年来，在精细有机合成方面，尤其是制新药方面，仍然有着开发与应用的价值和前景。     

一种方便有效地合成三烯酸与苯甲酸类化合物的方法

以烯酸炔丙基酯为反应原料,在碱性条件下,顺利发生分子内Ireland-Claisen重排/异构化反应,合成了标题化合物。实验结果表明,以乙腈作溶剂,在DBU(1,8-二氮双环[5.4.0]十一碳-7-烯)和TMSCl(三甲基氯硅烷)存在条件下,烯酸炔丙酯可顺利发生分子内重排反应,高收率地得到标题化合物,该合成路线具有反应条件温和、收率高等优点。     

2,5-二氯-4-氨基苯酚的合成

以对二氯苯为原料,经硝化、水合肼催化还原、Bamberger重排等反应合成了2,5-二氯-4-氨基苯酚;并对水合肼催化还原和Bamberger重排反应的条件进行了优化。在优化的条件下,2,5-二氯苯胲的收率达96.1%,2,5-二氯-4-氨基苯酚的收率达53.1%。该合成工艺具有反应周期短、条件温和、收率高和后处理简单等优点,有产业化前景。     

有机化学中氮原子重排反应及其应用的探讨

氮原子的重排反应在基础有机化学中非常重要,通过氮原子的重排可以有效地合成不同含氮化合物。掌握氮原子重排反应的规律特征,不仅可以加深人们对重排反应的理解和认识,也能更好地进行有机化学的学习。为了能在有机化学的教学中进一步加深对这类重排反应的掌握以及在更多的反应中熟练地运用这类重排,本文作者根据多年的有机化学教学经验,归纳和总结了有机化学中涉及氮原子重排的特征并对其应用作些探讨。     

不对称催化Claisen重排反应的研究进展

claisen重排反应在合成化学中是一类很重要的有机反应,也是合成γ,δ-不饱和酯的重要方法,但其不对称催化claisen重排反应却并不多,本文将重点介绍已经报道的不对称催化claisen重排反应。     

Semipinacol重排反应在有机合成中的应用

Semipinacol重排是构筑季碳的方法之一，已经被广泛应用于药物、天然产物、有机功能分子等中间体的合成。综述了Semipinacol重排反应在有机合成反应中的研究进展。     

2－芳基丙酸类消炎药合成中的重排反应

通过讨论缩酮结构、离去基活性和芳基迁移活性对重排反应的影响，总结了经重排反应合成２－芳基丙酸的一些规律，介绍了一条值得借鉴的不对称重排法合成萘普生的工艺路线     

金合欢基丙酮的合成与表征

对合成金合欢基丙酮的工艺路线进行了详细的探讨,确定了以芳樟醇为起始原料,经Car-roll重排反应、格氏反应、催化氢化和Carroll重排反应四步反应的合成路线,合成了金合欢基丙酮,总收率达50.9%。对最终产物进行了红外光谱、核磁共振谱和质谱的测试,证明所得产物为金合欢基丙酮。     

The combined C-H functionalization/Cope rearrangement: discovery and applications in organic synthesis

The development of methods for the stereoselective functionalization of sp(3) C-H bonds is a challenging undertaking. This Account describes the scope of the combined C-H functionalization/Cope rearrangement (CHCR), a reaction that occurs between rhodium-stabilized vinylcarbenoids and substrates containing allylic C-H bonds. Computational studies have shown that the CHCR reaction is initiated by a hydride transfer to the carbenoid from an allyl site on the substrate, which is then rapidly followed by C-C bond formation between the developing rhodium-bound allyl anion and the allyl cation. In principle, the reaction can proceed through four distinct orientations of the vinylcarbenoid and the approaching substrate. The early examples of the CHCR reaction were all highly diastereoselective, consistent with a reaction proceeding via a chair transition state with the vinylcarbenoid adopting an s-cis conformation. Recent computational studies have revealed that other transition state orientations are energetically accessible, and these results have guided the development of highly stereoselective CHCR reactions that proceed through a boat transition state with the vinylcarbenoid in an s-cis configuration. The CHCR reaction has broad applications in organic synthesis. In some new protocols, the CHCR reaction acts as a surrogate to some of the classic synthetic strategies in organic chemistry. The CHCR reaction has served as a synthetic equivalent of the Michael reaction, the vinylogous Mukaiyama aldol reaction, the tandem Claisen rearrangement/Cope rearrangement, and the tandem aldol reaction/siloxy-Cope rearrangement. In all of these cases, the products are generated with very high diastereocontrol. With a chiral dirhodium tetracarboxylate catalyst such as Rh(2)(S-DOSP)(4) or Rh(2)(S-PTAD)(4), researchers can achieve very high levels of asymmetric induction. Applications of the CHCR reaction include the effective enantiodifferentiation of racemic dihydronaphthalenes and the total synthesis of several natural products: (-)-colombiasin A, (-)-elisapterosin B, and (+)-erogorgiaene. By combining the CHCR reaction into a further cascade sequence, we and other researchers have achieved the asymmetric synthesis of 4-substituted indoles, a new class of monoamine reuptake inhibitors.     

绿色的Curtius重排及其新应用的研究

Curtius重排是众多重排反应中较为绿色的重排反应。它易反应,几乎无污染,产率高,因此其应用相当广泛,前景也很诱人。近年来,Curtius重排在精细有机合成中又有了令人注目的新应用。     

分子重排反应探析

对精细有机合成反应中常见的一些分子重排反应,进行分析归纳.其结果证实:在种种分子重排反应中,总是趋向于生成结构更稳定的碳正离子或碳负离子或自由基中间体及其产物.     

微波促进有机合成与研究

微波辐射技术可用于多种有机反应,如氧化反应、缩合反应、还原反应、酯化反应、烃烷基化反应、烯烃加成反应、羰基加成-消除反应、重排反应、环化和开环反应、Diels-Alder成环反应、取代反应、脱保护基反应、酰基化反应、芳基化反应、自由基反应、Tipson Cohen反应、产生二氯卡宾反应、脱羧反应、磺化反应、催化氢化反应、Bischler Napieralski反应、Fries重排反应、偶合反应、Mannich反应及金属有机化合物的合成反应等。     

Stereoselective construction of quaternary carbon stereocenters via a semipinacol rearrangement strategy

Quaternary carbon stereocenters are found in a broad range of organic compounds, including important bioactive natural products and medicinal agents. Given their ubiquity and the significant synthetic challenges they present, quaternary carbon stereocenters have long attracted great interest from synthetic organic chemists. Numerous efforts have been devoted to their construction, leading to a spectrum of strategies for creating stereogenic quaternary carbon centers. In this context, the semipinacol rearrangement has proven successful. In this extension of the pinacol rearrangement, the 1,2-carbon-to-carbon migration in a 1,2-diol has been expanded to include leaving groups other than the hydroxyl group. Over the past decade, our laboratory has explored the semipinacol rearrangement strategy for the stereoselective construction of quaternary carbon stereocenters. We have investigated various substrates, including 2,3-epoxy alcohols (also termed α-hydroxy epoxides), 2,3-aziridino alcohols, and allylic alcohols. Several promoters that effect the semipinacol rearrangement have been identified, including Lewis acids based on Al, Sm, B, Zn, and Ti for the rearrangement of α-hydroxy epoxides and 2,3-aziridino alcohols; cationic halogen species for the rearrangement of allylic alcohols; and cinchona alkaloids and chiral phosphoric acid for the asymmetric semipinacol rearrangement. Our research efforts have led to a series of valuable synthetic methods, including (1) a tandem semipinacol rearrangement and Meerwein-Ponndorf-Verley reduction, (2) a tandem semipinacol rearrangement and Tishchenko reaction, (3) a tandem semipinacol rearrangement with either an allylation or a propargylation, (4) a tandem semipinacol rearrangement and Schmidt reaction, (5) a semipinacol rearrangement of 2,3-aziridino alcohols, (6) a semipinacol rearrangement of allylic alcohols induced by halogen cation, (7) a tandem aziridination and semipinacol rearrangement of allylic alcohols, and (8) asymmetric semipinacol rearrangements with chiral organic catalysts. One hallmark of these reactions is the creation of stereogenic quaternary carbon centers with high levels of stereocontrol. In this Account, we describe the development of these synthetically useful methodologies and their successful application to the total syntheses of natural products. Our results demonstrate that the semipinacol rearrangement of carefully designed substrates constitutes an efficient approach to the stereoselective construction of quaternary carbon centers. These reactions have produced a broad array of useful compounds that lend themselves to further elaboration. Furthermore, the total synthesis of a series of alkaloids, with significant bioactivity and intriguing molecular architecture, was achieved through these semipinacol rearrangement strategies, highlighting their synthetic value.     

Zirconocene and Si-tethered diynes: a happy match directed toward organometallic chemistry and organic synthesis

Characterizing reactive organometallic intermediates is critical for understanding the mechanistic aspects of metal-mediated organic reactions. Moreover, the isolation of reactive organometallic intermediates can often result in the ability to design new synthetic methods. In this Account, we outline synthetic methods that we developed for a variety of diverse Zr/Si organo-bimetallic compounds and Si/N heteroatom-organic compounds through the detailed study of zirconacyclobutene-silacyclobutene fused compounds. Two basic components are involved in this chemistry. The first is the Si-tethered diyne, which owes its rich reactive palette to the combination of the Si-C bond and the C≡C triple bond. The second is the low-valent zirconocene species Cp(2)Zr(II), which has proven very useful in organic synthesis. The reaction of these two components affords the zirconacyclobutene-silacyclobutene fused compound, which is the key reactive Zr/Si organo-bimetallic intermediate discussed here. We discuss the three types of reactions that have been developed for the zirconacyclobutene-silacyclobutene fused intermediate. The reaction with nitriles (the C≡N triple bond) is introduced in the first section. In this one-pot reaction, up to four different components can be combined: the Si-tethered diyne can be reacted with three identical nitriles, with differing nitriles, or with a nitrile and other unsaturated organic substrates such as formamides, isocyanides, acid chlorides, aldehydes, carbodiimides, and azides. Several unexpected multiring, fused Zr/Si organo-bimetallic intermediates were isolated and characterized. A wide variety of N-heterocycles, such as 5-azaindole, pyrrole, and pyrroloazepine derivatives, were obtained. We then discuss the reaction with alkynes (the C≡C triple bond). A consecutive skeletal rearrangement, differing from that observed in the reactions with nitriles, takes place in this reaction. Finally, we discuss the reaction with the C═X substrates (where X is O or N), including ketones, aldehydes, and isocyanides. Oxa- and azazirconacycles are formed via a new skeletal rearrangement. Our results show that the zirconocene and the Si-tethered diyne cooperate as a "chemical transformer" after treatment with various substrates, leading to a diverse range of cyclic Zr/Si organo-bimetallic compounds. This mechanism-derived synthesis of organometallic and organic compounds demonstrates that the investigation of metal-mediated reactions and the isolation of reactive organometallic intermediates not only contribute to the understanding of complex reactions but can also lead to the discovery of synthetically useful methods.     

三甲基氯硅烷在有机合成中的应用进展

三甲基氯硅烷是最重要的有机硅试剂之一,在有机合成反应中用于基团的保护、作氯化剂及反应的活化剂等。综述了三甲基氯硅烷的合成方法及其在加速有机反应、提高反应收率和选择性等方面的主要应用。     

固相有机合成及其在精细化工中的应用与前景

论述了近期固相有机合成研究方面的一些最新进展和典型反应类型。由于固相反应的特征 ,多数固相有机反应表现出较溶液中更高的反应效率和更好的选择性 ,在某些情况下 ,利用光活性主体和反应物形成包合物 ,可实现对映选择性的不对称固相合成。还重点阐述了固相有机合成在精细化工生产中的应用 ,特别列举了有机、高分子材料、催化剂和药物等一些典型的精细化工产品的生产实例 ,因为固相有机合成具有节能、高效、降耗和减污等优点 ,是未来精细化工生产中重要的绿色生产方式 ,发展前景广阔。     

有机锆络合物在高选择性催化反应中的应用

有机锆络合物可以高选择性地催化环辛二烯加氢、烯烃与２－甲基吡啶偶合反应、环酮与醛、醇交叉缩合反应、ＭＰＶ型酮还原和ＯＰＰ型醇氧化反应及多羟基化合物酰基化等反应．这些反应在有机合成中具有应用价值。     

关于有机化学反应中的原子经济性探讨

探索具有原子经济性的反应是绿色化学的重要研究内容,是当今合成策略的一个重要组成部分。通过有机化学反应中重排反应、加成反应和异构化反应等对原子经济性进行了探讨