氯自由基介导的光催化芳基醚C(sp^(3))−H氧化生成酯

饱和的碳氢键氧化是合成化学和化学工业中一类重要的化学反应.然而,饱和C(sp^(3))−H键离解能(BDEs)较高、极性较弱,导致了底物难以活化和催化转化效率较低等问题.在过去的几十年,C(sp^(3))−H键的定向活化转化取得了重要的进展.其中,关于C(sp^(3))−H键催化氧化的研究主要涉及一些键能低的、预活化的C−H键,包括苄基型、亚甲基型、脂肪族X−CH_(2)(X=O,N)和甲苯等,含有未活化C(sp^(3))−H键的复杂化合物的选择性氧化仍具有挑战性.例如,芳基醚C(sp^(3))−H键功能化通常采用计量的过氧化物氧化剂,或者通过单电子氧化和碱促进的去质子化进一步构建C−C/C−N键,产物选择性较低,也带来了一些不利的环境影响.因此,有必要开发高效、温和的芳基醚C(sp^(3))−H键选择氧化方法,并将其应用于有机合成和药物开发.近年来,光催化C(sp^(3))−H键氧化因其操作简便、氧化还原中性等优点,已发展成为一种有用且多样的催化研究工具.本文发展了一种利用氧气作为氧化剂,在可见光驱动下选择性地将芳基醚C(sp^(3))−H键氧化成为甲酸苯酯类产物的新方法.使用Mes-10-phenyl-Acr^(+)−BF_(4)^(-)光催化剂,高效活化多种氯源(如盐酸、无机氯盐和有机氯化物)得到氯自由基,由于其具有较高的氧化能力(+2.03 V vs.SCE)和对氢原子的亲和力,能够通过氢原子转移过程活化芳基醚C(sp^(3))−键,攫取氢自由基得到相应的烷基碳自由基(•CH_(2)OPh)中间体,进一步被分子氧选择氧化得到酯类目标产物.研究结果表明,多种链状芳基醚和不同取代(如给电子基和吸电子基)芳基醚均可发生氧化反应,高收率地合成了一系列官能团丰富的甲酸苯酯类化合物.本文方法具有反应条件温和、操作简单、官能团耐受性好以及可规模化放大等优点,并且少量的水对反应没有明显影响.机理实验研究结果表明,芳基醚C(sp^(3))−H键的断裂是反应过程的决速步骤.紫外可见吸收光谱结果表明,氯离子与催化剂之间的相互作用强于底物,并且自由基捕获实验证实反应体系中存在氯自由基和烷基碳自由基物种,表明反应经历自由基路径.此外,电子顺磁共振测试结果表明,反应过程中存在单线态氧物种,可能是激发态的光催化剂直接与氧气发生能量转移得到;同位素实验(18O)揭示了甲酸苯酯类化合物氧的来源.综上,本文实现了温和条件下光催化芳基醚C(sp^(3))−H键选择氧化反应,高收率合成了一系列甲酸苯酯类化合物.该方法避免了化学计量的过氧化物和碱等添加剂的使用以及底物的过度氧化,阐明了催化反应机制,为其他醚类化合物的C(sp^(3))−H键氧化功能化提供了新思路,为后续化学合成和药物开发提供了参考和启示.

光催化甲苯衍生物、环烷烃与无机亚磺酸盐的位点选择性C(sp^(3))-H砜基化

烃类是最基础的有机分子之一,具有品种丰富、来源广泛、价格低廉等优势,其多样性、选择性转化一直备受合成化学家关注.然而,这些化合物中通常存在多个键能高、极性低、相互间差异性小的C(sp^(3))-H键,因此,实现高效、选择性C-H官能化极具挑战性.近年来,可见光催化广泛应用于有机合成中,与氢转移催化相结合所发展的可见光氢转移光催化策略在C(sp^(3))-H官能化反应中展现了较大的潜力,特别是为化学、位点、立体选择性等问题的解决带来了新机遇.尽管如此,能在激发态有效切断烷烃、环烷烃等中未活化的C(sp^(3))-H键,被用于直接氢转移光催化的催化剂种类很少,主要局限于十钨酸盐、芳香酮衍生物等,因此,发展新型氢转移光催化剂和新反应具有重要意义.近期人们发现,一种共轭多元醌分子(5,7,12,14-并五苯四酮,PT)具有较好的光物理性质、电化学性能及溶解性,可被用作直接氢转移光催化剂.为了深入研究其催化活性及在惰性烃类化合物转化中的应用,本文利用PT与铜盐协同作用,开发了一种高效、高选择性的C(sp^(3))-H砜基化反应,以无机亚磺酸盐作为砜基化试剂,将一系列甲苯衍生物、环烷烃、药物类似物等转化为具有潜在生物活性和重要合成应用的砜类产物.该反应条件温和、操作简单,不需要使用贵金属催化剂和配体,反应原料均已商品化且价格较便宜.通过自由基淬灭与捕获、自由基钟、控制实验、荧光淬灭等机理实验,证明了反应的自由基历程和铜介导的金属有机过程.X射线光电子能谱证明过程中伴随着零价铜的产生,反应仅需要1.2当量的二价铜盐作为氧化剂,为多样性C‒H官能化反应提出了新的策略和路径.此外,该方法还成功应用于药物类似物的后期官能化,展现了良好的官能团兼容性和位点选择性,进一步证明了其应用价值.综上所述,本文以一种商品化的共轭多元醌作为直接氢转移光催化剂,铜盐为氧化剂,无机亚磺酸盐为砜基化试剂,开发了一种经济低毒、温和易操作的甲苯衍生物、环烷烃C(sp^(3))-H官能化新方法,为砜类化合物的合成与开发利用提供了高效、高选择性的途径,也为药物分子后期官能化提供了有效的手段.

Efficient Photolytic Halogenation and Oxidation of Unactivated Alkyl sp^(3) C—H Bonds with Iodine(III)

A metal-free,green,and sustainable functionalization of unactivated alkyl sp^(3) C—H bonds is reported using iodine(III)as a feasible dehydrogenation agent under visible light or KBr,and alkyl chlorides,bromides,alcohols,and ketones could be constructed by addition of different coupling reagents.Cheap and safe iodobenzene diacetate was used to form a radical to activate the alkyl sp^(3) C—H bond in a highly efficient manner,which can construct different alkylation products by adding corresponding coupling reagents.

Synthesis of biheteroaryls via 2-methyl quinoline C(sp^(3))-H functionalization under metal-free conditions

An acetic acid-promoted C(sp^(3))-H functionalization of 2-methyl quinoline,enaminoesters and elemental sulfur for the synthesis of 3,4,5-trisubstituted isothiazoles under metal-free conditions has been developed.This approach provides viable access to various 5-(quinolin-2-yl)isothiazoles in moderate to good yields with good functional group tolerance.Moreover,the success of the gram-scale reaction gives this reaction a great potential application.

电化学促进未活化C(sp^(3))—H官能团化研究进展

有机电合成以无痕电子代替传统的化学氧化剂或还原剂,具有绿色易放大等优势.未活化C(sp^(3))—H键的官能团化可以将目标官能团直接引入分子中进行修饰,避免预官能团化,兼具原子经济性和步骤经济性.随着有机电合成发展的日益成熟,电化学促进未活化C(sp^(3))—H官能团化成为了有机合成的研究热点之一.根据官能团类型对反应进行分类,总结了近年来涉及未活化C(sp^(3))—H官能化的研究成果,重点分析了反应优势、底物特点以及反应机理,最后展望了面临的挑战及未来的发展趋势.

新型C3-含硅基取代手性脯氨酸型催化剂的高效构筑

为将C-H活化策略应用于手性有机催化剂的开发,选择以L-脯氨酸为原料、C(sp^(3))-H硅烷化反应为关键步骤,设计合成了两种新型的C3-三甲基硅基取代的手性脯氨酸催化剂,并将其分别应用于对硝基苯甲醛与丙酮的分子间不对称aldol反应和亚胺与β-甲基丁醛的分子间不对称Mannich反应,均可以良好对映选择性实现目标产物的合成.该策略有效丰富了脯氨酸结构的修饰手段,为新型含硅小分子催化剂的开发提供了新方法.

无金属条件下芳基酮与二甲亚砜的α-C(sp^(3))-H亚甲基化反应合成γ-酮亚砜

芳基酮通过C(sp^(3))-H键官能化与二甲亚砜发生直接的α-C(sp^(3))-H亚甲基化反应生成γ-酮亚砜,该方法适用于各种芳基酮.此外,二甲基亚砜(DMSO)在反应中不仅用作溶剂,而且用作含硫单元.这种转化的实际价值在于γ-酮亚砜的高效和稳健的一锅合成法,并在初步实验的基础上,提出了一种可能的反应机理.

Recent advances in sulfenylation of C(sp^3)-H bond under transition metal-free conditions

In recent years,the transition metal-free sulfenylation of C-H bond for C-S formation has been rapidly advanced and has become an eco-friendly synthetic tool for pharmacists and organic chemists.Various natural or bioactive molecules such as(hetero)arenes,olefins,carbonyl compounds,alkanes,have been employed for sulfenylating reactions.This review will focus on the recent five-year advances in C-S bond formation via direct sulfenylation of C(sp^3)-H bonds under metal-free conditions and elaborate their mechanisms from a new perspective.

C(sp^(3))-H bond functionalization of oximes derivatives via 1,5-hydrogen atom transfer induced by iminyl radical

Oximes derivatives have been vastly used in organic synthesis. In this review, C(sp^(3))-H bond functionalization of oximes derivatives via iminyl radical induced 1,5-hydrogen atom transfer was discussed. According to the different type of products, this review was divided into three parts: (1) C(sp^(3))-H bond functionalization for C-C bond formation. (2) C(sp^(3))-H bond functionalization for C-N bond formation. (3) C(sp^(3))-H bond functionalization for C-S, C-F bond formation.

Nano palladium catalyzed C(sp^(3))-H bonds arylation by a transient directing strategy

Reported herein is the first example of heterogeneous palladium catalyzed C(sp^(3))-H bonds arylation by a transient-ligand-directed strategy.Using supported palladium(metallic state) na nopariticles as catalyst,a wide range of aryl iodides undergo the coupling with various o-methylbenzaldehyde derivatives to assemble a library of highly selective and functionalized o-benzylbenzaldehydes.The stability of the catalyst was easily recovered four runs without significant loss of activity.The XPS analysis of the catalyst before and after reaction indicated that the reaction might be carried out by a catalytic cycle starting with Pd~0.

Dimensional Reduction of Eu-Based Metal-Organic Framework as Catalysts for Oxidation Catalysis of C(sp^(3))-H Bond

Comprehensive Summary Developing new catalysts for highly selectivity and conversion of saturated C(sp^(3))-H bonds is of great significance.In order to obtain catalysts with high catalytic performance,six Eu-based MOFs with different structural characteristics were obtained by using europium ions and different organic acid ligands,namely Eu-1~Eu-6.Eu-1,Eu-2 and Eu-3 featured three-dimensional structures,while Eu-4 and Eu-5 featured two-dimensional structures.

Recent advances in directα-C(sp^(3))-H bond functionalization of thioethers

Thioether skeletons are widely present in drugs,natural products,functional materials,and life science.In the past decade,the selective C–H functionalization of thioethers has been extensively studied to construct novel thioether derivatives.This mini-review systematically introduces the recent advances in the field of the directα-C(sp^(3))-H functionalization of thioethers.

Alumina-supported heteropoly acid:An efficient catalyst for the synthesis of azaarene substituted 3-hydroxy-2-oxindole derivatives via C(sp^3)-H bond functionalization

A method of C（sp^3）-H bond functionalization of methyl azaarenes catalyzed by alumina-supported heteropoly acid and addition to isatins was developed. This transformation could be used for the synthesis of biologically important 3-hydroxy-2-oxindole derivatives in good to excellent yields and the catalyst could be reused for six times without significant decrease in activity.

基于羧酸衍生物远程γ-C(sp^(3))–H键官能团化研究进展

碳氢键选择性活化是化学领域中最基本和最具挑战性的问题之一,在合成各种生物活性物质中具有重要的作用.羧酸及其衍生物是最易获得的原料之一.通常羧酸的α-和β-C(sp^(3))–H键官能化较为容易,而γ-和δ-C(sp^(3))–H因距离较远则难以官能化.因此,发展简便、高效的方法实现羧酸及其衍生物远程C(sp^(3))–H键官能团化成为近年研究热点之一.本文根据不同的反应分类,综述了近些年在不同催化条件下基于羧酸衍生物的远程γ-C(sp^(3))–H键官能团化反应研究进展,详细讨论了反应底物普适性、反应机理和应用,并对该领域的发展前景和局限性进行了总结.

导向基辅助的过渡金属催化C(sp^(3))—H键氮宾插入反应研究进展

过渡金属催化C(sp^(3))—H键活化形成碳-氮键的反应一直是具有挑战性且热门的研究领域.过渡金属催化的C(sp^(3))—H胺化策略为形成C—N键提供了更为直接高效的方式.随着碳-氢键活化领域的蓬勃发展,人们发展出了丰富多样的导向基和过渡金属催化体系,为通过内轨机制实现C(sp^(3))—H胺化提供了有效工具.近年来,导向基辅助的C(sp^(3))—H键胺化反应取得了重要进展,许多基于不同过渡金属的催化体系和廉价高效的胺化试剂得以开发.综述了近十年来在导向基团辅助下,过渡金属催化C(sp^(3))—H氮宾插入反应的研究进展.

Nucleophilic Radicals as Hydrogen Atom Abstractors in C(sp3)-H Functionalization Reactions

Hydrogen atom transfer(HAT)is an elementary mechanistic step in organic synthesis.The photoredox-catalyzed HAT has transformed organic synthesis by enabling the activation and subsequent cross-coupling of traditionally inert yet ubiquitous C(sp^(3))-H bonds.

C(sp^3)–H bond functionalization of non-cyclic ethers by decarboxylative oxidative coupling with α,β-unsaturated carboxylic acids

A copper-catalyzed decarboxylative oxidative coupling of α,β-unsaturated carboxylic acids with non-cyclic ethers is developed.This method provides a new approach for C(sp^3)–H bond functionalization of non-cyclic ethers. Mechanism study shows the reaction involves a radical process.

Direct C(sp^(3))-H Sulfonylation of Xanthene Derivatives with Sodium Sulfinates by Oxidative Copper Catalysis

By employing a readily available CuCI/DDQ catalyst system,we herein report a direct C(sp^(3))-H sulfonylation of xanthene derivates with odorless sodium sulfinates.Various 9H-xanthenes,thioxanthenes,and 9,10-dihydroacridines are efficiently transformed into the desired benzylic sulfonyl products via a radical/radical cross-coupling process,proceeding with the merits of broad substrate scope,operational simplicity,good functional group compatibility,and mild reaction conditions.

BrΦnsted acid-promoted ‘on-water’ C(sp^3)-H functionalization fot the synthesis of isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine derivatives targeting the SKP2-CKS1 interaction

The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community.In this communication,we report an efficient BrΦnsted acid-promoted C(sp^3)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine hybrids from 5-methyl-7-(2,4,6-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,2-formylbenzoic acid and various anilines.The title compounds were generated in high to excellent yields(up to 96%)regardless of the electronic nature and steric effects of the substituents.In this reaction,an isoindolinone scaffold,one C-C single bond,and two C-N bonds were formed simultaneously with high atom economy.In this work,we have envisioned that the methyl group linked to the electron-deficient Nheterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry.Besides,the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.

通过C(sp^(3))-H键活化构建C-P键合成氨基膦酸酯类化合物

氨基膦酸酯及其衍生物是一类重要的有机化合物,因其具有抗菌、抗真菌、酶抑制剂和催化抗体活性而广泛应于药物化学和农业化学。通过C(sp^(3))-H键活化构建C-P键是合成氨基膦酸酯衍生物重要方法之一。本文以过渡金属体系和非金属体系进行分类,介绍了近年来通过C(sp^(3))-H键活化方法构建C-P键合成氨基膦酸酯类化合物的研究进展。