一种构建多取代吡唑的新策略

以简单苯乙炔与醛酮加成得到的炔丙醇作为原料,在外在氧化剂(吡啶氮氧)和金催化剂存在的条件下,经历α-羰基金卡宾中间体和σ键迁移得到1,3-二酮化合物,再简单处理后与水合肼反应,以较好的收率得到多取代的具有潜在生物及药理活性的吡唑类化合物.形成α-羰基金卡宾和扩环成酮的策略也可以实现在串联反应中,由一步卡宾关环衔接,得到结构新颖的多环双酮类化合物.     

N-杂环卡宾的反应及应用

自从1991年Arduengo第一次分离得到稳定的游离N-杂环卡宾以后,N-杂环卡宾金属络合物的研究在近几年来得到了迅速的发展。N-杂环卡宾的反应性能较高,它们与周期表中几乎所有的元素都能发生反应。N-杂环卡宾金属络合物对许多反应有催化作用,它们是一类有潜在应用价值的催化剂。本文对近年来相关的研究成果进行了综述。     

含羟基手臂双咪唑鎓氯盐的合成及其Pd络合物对Suzuki-Miyaura交叉偶联反应的催化活性

合成了一种新型含羟基手臂的双咪唑鎓氯盐(L.2HCl)。N2保护下L.2HCl与Pd(OAc)2原位制备N-杂环卡宾-Pd络合物。以DMF-H2O为溶剂,K2CO3为碱,该络合物催化溴代芳烃和芳基硼酸的Suzuki-Miyaura交叉偶联反应合成取代联苯,收率75%～99%。     

金属氮杂环卡宾配合物的抗肿瘤活性研究进展

自1978年顺铂成功地被开发成癌症临床治疗药物以来,金属配合物作为小分子抗癌药物的开发成为人们的研究热点。其中,氮杂环卡宾能与多种过渡金属中心形成稳定的共价键,这种特殊的稳定性使得金属氮杂环卡宾配合物具有被开发成药物的潜能。近年来,金属氮杂环卡宾配合物被发现具有良好的抗癌活性,激发了广大无机药物化学研究者的研究热情。综合笔者课题组在金属氮杂环卡宾抗肿瘤配合物方面的前期研究,本文将对银、金、铑和铂氮杂环卡宾配合物的抗肿瘤活性及作用机制进行综述,以期为新型金属氮杂环卡宾抗肿瘤化合物的设计合成提供参考。     

N-杂环卡宾及其金属络合物的合成*

由于其强给电子能力、结构易修饰性和拓扑学特性,N-杂环卡宾成为继有机膦配体之后又一类重要的配体。其金属络合物在均相及不对称催化领域的催化性能是近期研究的热点,已有许多成功的结果。本文综述了近年来N-杂环卡宾及其金属络合物以及N-杂环卡宾的重要前体咪唑盐的合成方法。金属-N-杂环卡宾络合物的合成方法包括：(a)游离卡宾与金属化合物直接络合;(b)咪唑盐与金属化合物在强碱作用下络合;(c)利用Ag-NHC通过卡宾配体转移方法制备新的金属络合物。关于N-杂环卡宾前体的合成途径主要有：(a)乙二醛、伯胺和多聚甲醛的缩合反应;(b)卤代烷与咪唑及其取代咪唑的烷基化反应;(c)原甲酸酯与1,2-二胺的成环反应;(d)肼或酰胺与酸酐的环化反应;(e)用Na/K对环硫脲化合物的还原反应。     

亮点介绍

<正>镍-氮杂环卡宾催化吡啶区域和对映选择性C—H环化反应J. Am. Chem. Soc. 2019, 141, 5628～5634吡啶是一类重要的杂环,广泛存在于药物和配体结构中.据统计,吡啶是美国食品药品监督管理局(FDA)批准上市的药物结构中出现最多的含氮芳香杂环.因而,吡啶类化合物的构建和修饰方法研究有重要意义.其中,吡啶     

氮杂环卡宾与过渡金属共催化反应研究进展

近年来,氮杂环卡宾作为有机小分子催化剂在共催化领域取得了飞速发展,氮杂环卡宾通过与Lewis酸、Brønsted酸、Brønsted碱、氢键等不同催化模式相结合,可以有效提升惰性底物的活性和催化体系的立体控制能力,该策略已经成为复杂手性分子骨架合成的重要工具.相对而言,由于氮杂环卡宾与过渡金属的强配位能力,其与过渡金属共催化反应依旧是氮杂环卡宾在共催化领域中长期存在的挑战性工作.目前,氮杂环卡宾在与钯、铜和钌的共催化反应中取得了重要进展,通过配体和反应体系中碱性强弱的调控,可以有效实现氮杂环卡宾与过渡金属配位的可控调节,避免催化剂失活的同时提升反应体系催化活性.这一策略已经被成功用于一些活性分子骨架构建.本文将对该领域中的研究进展进行介绍.     

氮杂环卡宾在有机催化中的研究进展

介绍了氮杂环卡宾作为有机催化剂的发展历史和催化机理,综述了近年来氮杂环卡宾在有机催化领域中的研究成果.     

N-氟代双苯磺酰胺介导的氮杂卡宾氧化催化合成过氧酯及酰胺的研究

在N-氟代双苯磺酰胺(简称NFSI)介导的氮杂卡宾催化体系下,首次实现了有机催化叔丁基过氧酯的合成,该反应同样可以用于合成酰胺.以不饱和醛为起始原料,在5 mol%的氮杂卡宾以及NFSI的体系中以及室温的条件下最高能够得到大于95%收率的叔丁基过氧酯.该反应具有条件温和、低催化剂用量(最低可降至2 mol%)、收率高、底物适用范围广等优点.     

氮杂环卡宾(NHC)催化下多取代环戊烯的串联合成

在氮杂环卡宾(N-heterocycliccarbene,NHC)催化下,α,β-不饱和羧酸经过原位活化后与2-(2-氧代-2-芳乙基)丙二腈发生Michael加成、羟醛缩合、脱羧等反应,一锅法合成了多取代环戊烯类化合物.该方法具有底物范围广、原料易得、反应条件温和、产率高、操作简便等优点,为多官能化环戊烯类化合物的高效合成提供了新思路.     

Synthesis of Gold(I)−Trifluoromethyl Complexes and their Role in Generating Spectroscopic Evidence for a Gold(I)−Difluorocarbene Species

Readily prepared and bench-stable [Au(CF₃)(NHC)] compounds were synthesized by using new methods, starting from [Au(OH)(NHC)], [Au(Cl)(NHC)] or [Au(L)(NHC)]HF₂ precursors (NHC=N-heterocyclic carbene). The mechanism of formation of these species was investigated. Consequently, a new and straightforward strategy for the mild and selective cleavage of a single carbon/fluorine bond from [Au(CF₃)(NHC)] complexes was attempted and found to be reversible in the presence of an additional nucleophilic fluoride source. This straightforward technique has led to the unprecedented spectroscopic observation of a gold(I)−NHC difluorocarbene species.     

Continuous Flow Synthesis of [Au(NHC)(Aryl)] (NHC=N-Heterocyclic Carbene) Complexes

The use of weak and inexpensive bases has recently opened promising perspectives towards the simpler and more sustainable synthesis of Au(I)-aryl complexes with valuable applications in catalysis, medicinal chemistry, and materials science. In recent years, continuous manufacturing has shown to be a reliable partner in establishing sustainable and controlled process scalability. Herein, the first continuous flow synthesis of a range of Au(I)-aryl starting from widely available boronic acids and various [Au(NHC)Cl] (NHC=N-heterocyclic carbene) complexes in unprecedentedly short reaction times and high yields is reported. Successful synthesis of previously non- or poorly accessible complexes exposed fascinating reactivity patterns. Via a gram-scale synthesis, convenient process scalability of the developed protocol was showcased.     

Primary amino-functionalized N-heterocyclic carbene ligands as support for Au(I)···Au(I) interactions: structural, electrochemical, spectroscopic and computational studies of the dinuclear [Au2(NH2(CH2)2imMe)2][NO3]2

The N-heterocyclic carbene (NHC) precursor, 1-(2-aminoethyl)-3-methylimidazolium nitrate, [NH(2)(CH(2))(2)imMe)]NO(3) ([3][NO(3)]) reacted with Ag(2)CO(3) in dimethyl sulfoxide readily yielding a Ag(I)-(NHC-NH(2)) complex presenting limited stability in solution. The in situ carbene transfer reaction of the latter with [Au(tht)Cl] afforded the first example of a dinuclear gold(I) complex [Au(2)(NH(2)(CH(2))(2)imMe)(2)][NO(3)](2) ([5][NO(3)](2)) bearing a primary amino-functionalized NHC ligand. The complex has been characterized by NMR, mass spectrometry, X-ray crystallography and cyclic voltammetry; the electrochemical behaviour and photophysical properties of [5][NO(3)](2) have been also investigated and the experimental data have been compared with density functional theory (DFT) and Time Dependent (TDDFT) calculations. Single-crystal structural studies showed that the Au(I)-carbene compound contains dinuclear (AuL)(2) cations in which pairs of gold(I) centres are linked by a pair of bridging ligands, with a Au···Au aurophilic contact of 3.2332(17) ? that is maintained in solution as documented by the DFT calculations. Complex [5][NO(3)](2) is photoluminescent in solution at room temperature and the high energy emission peak at 410 nm is remarkably shifted with respect to the absorption band centered at 260 nm.     

The first example of a two‐coordinated AuI atom bonded to an FeII atom and an N‐heterocyclic carbene (NHC) ligand

The aurophilicity exhibited by Au^I complexes depends strongly on the nature of the supporting ligands present and the length of the Au–element (Au—E) bond may be used as a measure of the donor–acceptor properties of the coordinated ligands. A binuclear iron–gold complex, [1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene‐2κC²]dicarbonyl‐1κ²C‐(1η⁵‐cyclopentadienyl)gold(I)iron(II)(Au—Fe) benzene trisolvate, [AuFe(C₅H₅)(C₂₇H₃₆N₂)(CO)₂]·3C₆H₆, was prepared by reaction of K[CpFe(CO)₂] (Cp is cyclopentadienyl) with (NHC)AuCl [NHC = 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene]. In addition to the binuclear complex, the asymmetric unit contains three benzene solvent molecules. This is the first example of a two‐coordinated Au atom bonded to an Fe and a C atom of an N‐heterocyclic carbene.     

Olefin metathesis catalyst: stabilization effect of backbone substitutions of N-heterocyclic carbene

Ruthenium olefin metathesis catalysts bearing an N-phenyl-substituted N-heterocyclic carbene (NHC) ligand that are resistant to decomposition through C-H activation have been prepared and tested in ring closing metathesis (RCM), cross metathesis (CM), and ROMP reactions. The N, N'-diphenyl-substituted NHC complex proved to be one of the most efficient catalysts in RCM to form tetrasubstituted olefins.     

Syntheses, crystal structures, reactivity, and photochemistry of gold(III) bromides bearing N-heterocyclic carbenes

Gold(I) complexes bearing N-heterocyclic carbenes (NHC) of the type (NHC)AuBr (3a/3b) [NHC = 1-methyl-3-benzylimidazol-2-ylidene (= MeBnIm), and 1,3-dibenzylimidazol-2-ylidene (= Bn(2)Im)] are prepared by transmetallation reactions of (tht)AuBr (tht = tetrahydrothiophene) and (NHC)AgBr (2a/2b). The homoleptic, ionic complexes [(NHC)(2)Au]Br (6a/6b) are synthesized by the reaction with free carbene. Successive oxidation of 3a/3b and 6a/6b with bromine gave the respective (NHC)AuBr(3) (4a/4b) and [(NHC)(2)AuBr(2)]Br (7a/7b) in good overall yields as yellow powders. All complexes were characterized by NMR spectroscopy, mass spectrometry, elemental analysis and single crystal X-ray diffraction. Reactions of the Au(III) complexes towards anionic ligands like carboxylates, phenolates and thiophenolates were investigated and result in a complete or partial reduction to a Au(I) complex. Irradiation of the Au(III) complexes with UV light yield the Au(I) congeners in a clean photo-reaction.     

Computational insight into a gold(I) N-heterocyclic carbene mediated alkyne hydroamination reaction

A gold(I) N-heterocyclic carbene (NHC) complex mediated hydroamination of an alkyne has been modeled using density functional theory (DFT) study. In this regard, alkyne and amine coordination pathways have been investigated for the hydroamination reaction between two representative substrates, namely, MeC≡CH and PhNH(2), catalyzed by a gold(I) NHC based (NHC)AuCl-type precatalyst, namely, [1,3-dimethylimidazol-2-ylidene]gold chloride. The amine coordination pathway displayed a lower activation barrier than the alkyne coordination pathway. The catalytic cycle is proposed to proceed via a crucial proton-transfer step occurring between the intermediates [(NHC)AuCH═CMeNH(2)Ph](+) (D) and [(NHC)Au(PhNHMeC═CH(2))](+) (E), the activation barrier of which was found to be significantly reduced by a proton relay mechanism process assisted by the presence of any adventitious H(2)O molecule or even by any of the reacting PhNH(2) substrates. The final hydroaminated enamine product, PhNHMeC═CH(2), was further seen to be stabilized in its tautomeric imine form PhN═CMe(2).     

Noble Metal Corrosion: Halogen Bonded Iodocarbenium Iodides Dissolve Elemental Gold—Direct Access to Gold–Carbene Complexes

A common method to dissolve elemental gold involves the combination of an oxidant with a Lewis base that coordinates to the gold surface, thus lowering the metal's redox potential. Herein we report the usage of organic iodide salts, which provide both oxidative power and a coordinating ligand, to dissolve gold under formation of organo-gold complexes. The obtained products were identified as Au^III complexes, all featuring Au−C bonds, as shown by X-ray single-crystal analysis, and can be isolated in good yields. Additionally, our method provides direct access to N-heterocyclic carbene (NHC-type) complexes and avoids costly organometallic precursors. The investigated complexes show dynamic behavior in acetonitrile and in the case of the NHC(-type) complexes, the involved species could be identified as a monocarbene [AuI₃(carbene)] and biscarbene complex [AuI₂(carbene)₂]⁺.     

N-Heterocyclic carbene–rhodium complexes as catalysts for hydroformylation and related reactions

Rhodium(I) complexes with N-heterocyclic carbenes (Rh–NHC) can be considered as important candidates for catalysts of hydroformylation of olefins. The high stability of Rh-C(NHC) bonding under reaction conditions allow to expect that NHC ligand will be present in coordination sphere of the catalytically active rhodium complex and therefore influences the reaction yield and regioselectivity. The potential applicability of Rh–NHC complexes containing chiral carbene ligand in asymmetric hydroformylation can be also considered. The excellent review articles relevant to application of Rh–NHC in hydroformylation have been published recently [1], [2], [3]. After that, important contributions to this subject, concerning theoretical and experimental studies, both structural and catalytic, have been reported. Therefore, the reactivity of Rh–NHC complexes can be discussed now in term of these new data. The up to now reported results indicate that the most promising and selective systems for hydroformylation can be composed from Rh–NHC complex and stoichiometric amount of electron-withdrawing phosphorus ligand.     

Stepwise synthesis of a hydrido, N-heterocyclic dicarbene iridium(III) pincer complex featuring mixed NHC/abnormal NHC ligands

We describe a stepwise synthesis of the hydrido, N-heterocyclic dicarbene iridium(III) pincer complex [Ir(H)I(C(NHC)CC(aNHC))(NCMe)] (3) which features a combination of normal and abnormal NHC ligands. The reaction of the bis(imidazolium) diiodide [(CH(imid)CHCH(imid))]I(2) (1) with [Ir(μ-Cl)(cod)](2) afforded first the mono-NHC Ir(I) complex [IrI(cod)(CH(imid)CHC(NHC))]I (2), which was then reacted with 2 equiv. of Cs(2)CO(3) in acetonitrile at 60 °C for 40 h to yield 3. These observations support our previously proposed mechanism for the formation of hydrido, N-heterocyclic dicarbene iridium(III) pincer complexes from the reaction of bis(imidazolium) salts with weak bases involving a mono-NHC Ir(I) intermediate. We describe the reactivity of the mono-NHC Ir(I) complex 2 under various conditions. By changing the reaction solvent from MeCN to toluene, we observed the cleavage of the imidazol-2-ylidene ring and the formation of an iminoformamide-containing mono-NHC Ir(I) complex [IrI(cod){[NHCH=CHN(Ad)CHO]CHC(NHC)}] (4). Complex 4 was also prepared in high yield from the reaction of 2 with strong bases (potassium tert-butoxide or potassium hexamethyldisilazane), via the initial formation of the complex [IrI(cod)(CH(NHC)CHC(NHC))] (5), which contains a coordinated NHC moiety and a free carbene arm, followed by subsequent hydrolysis of the latter. The bis(imidazolium) salt 1 can be deprotonated by strong bases to form the bis(carbene) ligand C(NHC)CHC(NHC) (6), which readily reacts with [Ir(μ-Cl)(cod)](2) to give the dinuclear complex [{IrI(cod)}(2)(μ-C(NHC)CHC(NHC))] (7), in which the N-heterocyclic bis(carbene) ligand bridges the two metals through the carbene carbon atoms.