Rh(Ⅲ)催化的N-甲氧基苯甲酰胺系列物选择性C-H氰基化反应（英文）

采用了最近热门的Rh(III)催化C-H键活化方法,以N-甲氧基苯甲酰胺系列物为反应底物,N-氰基-N-苯基对甲苯磺酰胺(NCTS)为氰基化试剂,高效合成了含氰基官能团产物.结果表明,该反应在碳酸银存在下,使用二氧六环作为反应溶剂,于80°C反应8 h生成的邻位氰基取代的N-甲氧基苯甲酰胺的产率较高.进一步研究表明,该反应具有好的区域选择性和底物/官能团适应性.一系列机理实验研究表明,该反应可能采用了一个内部的亲电取代机制及使用了C-H键切割步骤作为关键限速步骤.考虑到该反应产物包含有价值的结构单元-N-甲氧基甲酰胺和氰基取代基,因而有望用于现代有机合成中.     

光/铜共催化远程C—H键的不对称氰基化反应

以N-烷氧基邻苯二甲酰亚胺为底物, 利用光与铜共催化, 在蓝光照射下, 实现了远程C—H键不对称氰基化反应. 反应中涉及氧自由基的1,5-氢迁移过程, 结合铜催化自由基接力的策略, 以良好到优秀的对映选择性、单一的区域选择性得到了芳基取代的烷基醇类衍生物δ-位C—H键不对称氰基化产物. 该方法条件温和, 具有较好的官能团兼容性以及底物普适性, 为光学活性的δ-氰基醇类化合物的合成提供了高效方法.     

新型N-甲基-N-(2-溴苯基)-2-取代基-2-氰基酰胺的合成

以2-溴苯胺和氰乙酸为原料,经N-烷基化、酰胺化和α-烷基化反应合成了4种新型的N-甲基-N-(2-溴苯基)-2-取代基-2-氰基酰胺类化合物(5a~5d),其结构经1H NMR,13C NMR和HR-MS表征。在最佳反应条件[N-甲基-N-(2-溴苯基)-2-氰基乙酰胺(3)1.7 mmol,n(3)∶n(溴乙烷)=1∶1,DMF为溶剂,Cs2CO3为碱,于室温反应6 h]下,5a收率83%。     

氨基甲酸酯在C—H键活化中的应用

氨基甲酸酯广泛存在于天然产物、药物和农药分子中,同时也是一种常见的C—H键活化导向官能团。在过渡金属催化下,氨基甲酸酯可导向底物分子氨基邻位的C—H键活化,经六元环金属中间体,再与其他偶联试剂偶联实现新的官能团化。本文系统总结了其在C—H键活化反应中的应用,具体包括:(1)N-芳基氨基甲酸酯、氨基甲酸芳酯和氨基甲酸烯醇酯可在过渡金属Pd、Rh、Ru和Ir等催化下发生芳基邻位sp~2C—H键活化与官能团化反应,得到卤化、芳基化、环化和烯基化产物;(2)氨基甲酸烯醇酯可在Rh催化下发生烯基β-位sp~2C—H键活化与官能团化反应,得到烯基化和烯丙基化产物;(3)氨基邻位具有活性氢的N-烷基氨基甲酸酯可在Pd、Cu、Fe甚至无过渡金属催化下发生sp~3C—H键活化与官能团化反应,得到酰氧化、烷基化和芳基化产物。在芳香sp~2C—H键活化中,取代基的电子效应和空间位阻效应均对产物产率和选择性有重要影响。大多数情况下,给电子与空间位阻较小的取代基有利于反应的顺利进行。此外,当底物为N-烷氧羰基保护的苄胺、四氢异喹啉或1,2-二氢喹啉时,因氨基邻位独特的高活性,可在Cu、Fe甚至无金属催化剂或光催化下催化氨基邻位sp~3C—H键活化反应,还可以实现不对称诱导,获得非常高的对映选择性。希望本文总结的内容能促进氨基甲酸酯在C—H键活化反应中的进一步应用。     

氨基甲酸酯在C—H键活化中的应用

氨基甲酸酯广泛存在于天然产物、药物和农药分子中,同时也是一种常见的C—H键活化导向官能团。在过渡金属催化下,氨基甲酸酯可导向底物分子氨基邻位的C—H键活化,经六元环金属中间体,再与其他偶联试剂偶联实现新的官能团化。本文系统总结了其在C—H键活化反应中的应用,具体包括:(1)N-芳基氨基甲酸酯、氨基甲酸芳酯和氨基甲酸烯醇酯可在过渡金属Pd、Rh、Ru和Ir等催化下发生芳基邻位sp2C—H键活化与官能团化反应,得到卤化、芳基化、环化和烯基化产物;(2)氨基甲酸烯醇酯可在Rh催化下发生烯基β-位sp2C—H键活化与官能团化反应,得到烯基化和烯丙基化产物;(3)氨基邻位具有活性氢的N-烷基氨基甲酸酯可在Pd、Cu、Fe甚至无过渡金属催化下发生sp3C—H键活化与官能团化反应,得到酰氧化、烷基化和芳基化产物。在芳香sp2C—H键活化中,取代基的电子效应和空间位阻效应均对产物产率和选择性有重要影响。大多数情况下,给电子与空间位阻较小的取代基有利于反应的顺利进行。此外,当底物为N-烷氧羰基保护的苄胺、四氢异喹啉或1,2-二氢喹啉时,因氨基邻位独特的高活性,可在Cu、Fe甚至无金属催化剂或光催化下催化氨基邻位sp3C—H键活化反应,还可以实现不对称诱导,获得非常高的对映选择性。希望本文总结的内容能促进氨基甲酸酯在C—H键活化反应中的进一步应用。     

由α-氰基肉桂酸乙酯/N-溴代苯甲酰胺合成2-噁唑啉衍生物

作为重要的杂环化合物,合成新的2-噁唑啉衍生物以及发展其新的合成方法具有重要意义,为此以α-氰基肉桂酸乙酯衍生物为底物,以N-溴苯甲酰胺为反应试剂,在无水碳酸钠(相对于底物3为110%摩尔分数)促进下,在丙酮溶剂中,室温下,建立了合成相应2-噁唑啉衍生物的新方法,共合成了11个新化合物,其结构由核磁共振波谱仪(~1H NMR,~(13)C NMR)和高分辨质谱(HRMS)确认。结果显示,各种α-氰基肉桂酸乙酯衍生物(3a~3k)可被顺利的转化成相应的2-噁唑啉衍生物(5a~5k)。在室温下,丙酮作溶剂,以Na_2CO_3为促进剂时,相应产物的最高收率可达90%。不仅α-氰基肉桂酸乙酯衍生物(3)可被用作该反应的底物,而且α-乙氧甲酰基肉桂酸乙酯(6)也适用于该反应。实验结果还证明,除了N-溴代苯甲酰胺外,N-溴代对硝基苯甲酰胺(8)及N-溴代乙酰胺(9)也适用该反应,证明该方法具有广泛的适应性。根据实验结果,提出了可能的反应机理,该机理支持了形成2-噁唑啉衍生物的区域选择性。     

三价铑催化N-甲氧基苯甲酰胺与炔丙醇[4+1]环化合成异吲哚啉酮

含N杂环结构广泛存在于具有生物活性的药物或天然产物骨架中.本文开发了一个高效合成含N杂环骨架的方法,这类方法在近年来一直是研究热点.在最近几年,过渡金属催化C–H键活化并随后与不饱和键发生环化反应被认为是一种环境友好且原子经济性高的构建功能化杂环的方法.在这些金属催化的体系中,三价铑催化与炔烃的环化反应体系,被认为是一种高效且有实际意义的合成含N杂环的体系.在这类体系,特别是构建六元环的体系中,炔烃通常作为一个C2合成子被广泛应用.为了克服这一局限性,Chang课题组和本课题组分别独立报道了通过三价铑催化,炔烃与芳烃硝酮偶联合成吲哚啉化合物,其中炔烃作为一个C1合成子参与反应.另一方面,本课题组还报道了炔丙醇与吡咯烷苯甲酰胺通过C–H键活化合成1-异色满酮结构,其中由于电子效应,芳基-铑物种对于炔烃的插入是在炔烃的2位.基于上述工作,本文希望通过置换炔丙醇中芳基与烷基的位置,使芳基-铑物种对于炔烃插入的方向发生改变,进而生成联烯中间体,然后发生环化反应生成五元环内酰胺结构.异吲哚啉酮骨架结构也是一类重要的含N杂环结构,广泛存在于多种天然产物及药物分子中,其合成方法受到广泛关注.尽管此前已有三价铑催化C–H官能团化的方法来构建异吲哚啉酮骨架结构,但通常需要活性极高或易爆的化合物作为反应底物.因此,本文报道一类以简单的炔丙醇与N-甲氧基苯甲酰胺作为起始原料,通过一步[4+1]环化合成异吲哚啉酮骨架结构.本文完成了32个不同官能团取代的异吲哚啉酮骨架结构的合成,反应均可以以中等到良好的收率得到目标产物.另外还进行了放大实验,结果表明可以以克级规模制备异吲哚啉酮化合物,反应剩余的Ag2CO3以及生成的单质银可以回收(收率78%).总之,我们将N-甲氧基苯甲酰胺与炔丙醇在三价铑催化作用下通过C–H键活化的方法环化高效合成N-取代的异吲哚啉酮骨架结构,且该骨架结构含有一个手性中心.催化体系温和,官能团容忍度好.     

钯催化吲哚7位选择性直接芳基化反应

正J.Am.Chem.Soc.2016,138,495~498近年来,利用C—H键官能团化手段对吲哚骨架进行修饰受到化学家们的广泛关注.其中,吲哚2、3位的官能团反应已经很成熟,而对于吲哚苯环上的C—H键直接进行官能团化是一项非常具有挑战性的工作.南京大学化学化工学院史壮志课题组发展了一类二叔丁基取代的N-磷酰基作为导向基团,通过单晶衍射发现该类底物中,磷酰基上的氧原子是朝向吲哚7位上的C—H键.利用这类底物作为原料,以醋酸钯作为催化剂,芳基硼酸作为芳基源,2-     

光/电化学氧化诱导C–H键官能团化

C–H键活化及其官能团化一直被认为是合成化学的圣杯,光/电氧化诱导C–H键官能团化反应为追求更为绿色、原子经济性、步骤经济性更高的现代合成化学提供了新思路.我们借助可见光或电化学氧化诱导策略实现了直接C–H键官能团化,即底物无需预官能团化,无需外加氧化剂,可直接实现碳–碳以及碳–杂键的构建.通过光/电化学氧化诱导策略使得反应在更为温和的条件下进行,能够兼容更多官能团,并且为合成化学提供一条新的途径.近些年,该策略已经应用于不同化学环境C–H官能团化构建多种化学键.本文结合该领域的代表性工作,重点介绍本课题组近些年在光/电氧化诱导C–H键官能团化反应上的研究进展,并对这一领域的前景进行了展望.     

2-苯甲酰基嘧啶类化合物的合成与生物活性

2-嘧啶氧基-N-芳基苄胺类化合物结构经过两次骨架结构优化后得到2-苯甲酰基嘧啶类化合物二次先导结构.在二次先导结构基础上,共设计并合成了36个化合物,所有化合物结构经1H NMR、13C NMR、HRMS确认,并进行了室内杀菌活性筛选,对各部位取代基进行了逐次优化.结果表明2-苯甲酰基嘧啶类化合物中R1取代基以2位卤素或烷基取代的苯环或杂环活性最好;中间苯环6位引入氟原子活性保持;嘧啶环4,6位甲氧基取代活性较好,5位甲基取代活性大大降低;羰基被还原为羟基后活性消失.其中2,3-二氯-N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)苯氧基]-N-甲基苯甲酰胺(4AHl)、2,5-二氯-N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)苯氧基]-N-甲基苯甲酰胺(4AHn)及N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)-3-氟苯氧基]-N,2-二甲基苯甲酰胺(4AFd)对黄瓜白粉病的杀菌活性与对照样苯菌酮相当.     

Zinc-prolinamide complex catalyzed direct asymmetric aldol reactions in the presence of water

An efficient direct asymmetric aldol reaction with zinc triflate and prolinamides as combined catalysts is reported. A series of chiral prolinamides have been designed and used in the direct aldol reaction resulting in the desired products with excellent yields (up to 94% yield) and high enantioselectivities (up to 96% ee). Water was found to play a significant role in the formation of the aldol products, which suggests a new strategy in the design of new organic catalysts.     

Bi(OTf)3-Catalyzed Intramolecular Amination of Triazenylaryl Allylic Alcohols: A Stereoselective,High-Yield Synthesis of (E)-3-Alkenyl 2H-indazoles

An efficient Bi(OTf)₃-catalyzed synthesis of 3-alkenyl-2-pyrrolidine-2H-indazoles from triazenylaryl allylic alcohols via the intramolecular direct amination process is reported. Compared with the dodecyl benzenesulfonic acid (DBSA)-catalyzed method, the new method is more efficient and gives greater yields and functionality tolerance. Additionally, the 3-alkenyl-2-pyrrolidine-2H-indazoles can be transformed to a series of new products under different reaction conditions.     

Palladium-catalyzed direct C-H arylation of unactivated arenes with aryl Halides

An efficient palladium-catalyzed direct C-H arylation of unactivated arenes has been discovered. This method employs aryl halides as the direct coupling partners with arenes without using any external ligands. This catalysis opens a new methodology for the preparation of symmetrical as well as unsymmetrical biaryls in a user-friendly approach.     

Efficient synthetic method of Psammaplin A

A new concise and efficient synthetic method of Psammaplin A was developed. Psammaplin A was obtained with 50% overall yield in nine steps from p-hydroxybenzaldehyde and ethyl acetoacetate via Knoevenagel condensation and direct nitrosation as key steps. This method might be very efficient to construct a quite diverse library of Psammaplin A type analogs.     

Brønsted-acid-catalyzed activation of nitroalkanes: a direct enantioselective aza-Henry reaction

A direct asymmetric organocatalytic aza-Henry reaction has been developed in which a new bifunctional Br?nsted-acid-catalyzed activation of nitroalkanes provides an efficient access to alpha,beta-diamino acids with high dia- and enantioselectivities under mild and base-free reaction conditions.     

Amine‐Catalyzed Direct Photoarylation of Unactivated Arenes

Constructing biaryls through direct aromatic C? H functionalization of unactivated arenes has become a popular topic in organic chemistry. Many efficient methods have been developed. In this Communication, a direct arylation of unactivated arenes with a broad range of aryl iodides is reported. This reaction proceeds through a new type of amine‐catalyzed single electron transfer initiated radical coupling procedure to form biaryls in high yields under UV irradiation at room temperature. Only 20 mol% of TMEDA is used as the catalyst. No other additives are required for this transformation, thus avoiding the use of toxic transition metal catalysts, strong bases, or large amounts of other organic additives. This greener protocol provides a new strategy to achieve direct aromatic C? H functionalization and offers a new example of cost‐effective and environmentally benign access to biaryls.     

Proline–threonine dipeptide as an organocatalyst for the direct asymmetric aldol reaction

A new proline–threonine (H-Pro-Thr-OH) dipeptide has been demonstrated as an efficient organocatalyst for a direct asymmetric aldol reaction. It was found that this new peptide-based catalyst efficiently catalyzed the reaction between an aldehyde and acetone to provide β-hydroxy ketones in good yields with good enantioselectivities.     

A novel procedure for conversion of epoxides to α-hydroxyphosphonates with a trialkylphosphite mediated by LiClO4

A new method has been developed for the direct conversion of epoxides to α-hydroxyphosphonates by the reaction of a trialkylphosphite with the epoxide in 5 M lithium perchlorate in diethyl ether (LPDE). The reaction is highly regioselective and efficient with excellent yields under mild and neutral conditions.     

Formulation and implementation of direct algorithm for the symmetry-adapted cluster and symmetry-adapted cluster-configuration interaction method

We present a new computational algorithm, called direct algorithm, for the symmetry-adapted cluster (SAC) and SAC-configuration interaction (SAC-CI) methodology for the ground, excited, ionized, and electron-attached states. The perturbation-selection technique and the molecular orbital index based direct sigma-vector algorithm were combined efficiently with the use of the sparse nature of the matrices involved. The formal computational cost was reduced to O(N(2)xM) for a system with N-active orbitals and M-selected excitation operators. The new direct SAC-CI program has been applied to several small molecules and free-base porphin and has been shown to be more efficient than the conventional nondirect SAC-CI program for almost all cases. Particularly, the acceleration was significant for large dimensional computations. The direct SAC-CI algorithm has achieved an improvement in both accuracy and efficiency. It would open a new possibility in the SAC/SAC-CI methodology for studying various kinds of ground, excited, and ionized states of molecules.     

An amine sulfonamide organocatalyst for promoting direct, highly enantioselective α-aminoxylation reactions of aldehydes and ketones

A novel, pyrrolidine sulfonamide-based organocatalyst has been developed and used to catalyze direct, efficient and α-aminoxylation reactions of aldehydes and ketones with excellent regio- and enantioselectivities. Unlike l-proline, the new catalyst exhibits high activity and enantioselectivity when used in a variety of organic solvents.