Efficient synthesis of aminomethylated azaindoles and corresponding pyrrole-fused derivatives by copper-catalyzed domino multicomponent coupling and cyclization

Efficient methods for the synthesis of aminomethylated azaindole derivatives via domino copper-catalyzed multicomponent coupling and cyclization have been developed. Using various secondary amines and aldehydes, N-substituted 3-ethynyl-4-aminopyridine was converted to substituted azaindoles in moderate to excellent yields. By use of a 3,4-diaminopyridine derivative bearing two alkynyl groups, the corresponding pyrrole-fused azaindoles were synthesized by controlled stepwise cyclization.     

Azaindole derivatives

A comparative study of the dehydrogenation of azaindoles by chemical (under the action of quinones) and electrochemical (anode polarography at a rotating platinum disc electrode) methods has been made. The influence of substituents in positions 1 and 6 of the azaindole molecule on the ease of oxidation of the compounds has been investigated. The results are discussed using the method of correlation equations.For part XXVII, see [16].     

Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance

The regioselective functionalization of 7‐azaindole by controlled annular isomerism employing a directed metalation‐group migration is reported. The N7 carbamoyl azaindoles undergo regioselective metalation and quenching with an electrophile to furnish C6‐substituted derivatives which, in the presence of a catalytic amount of ClCONR₂ promotes a carbamoyl group shift or dance from N7 to N1. A second directed metalation/electrophile quench sequence leads to 2,6‐substituted azaindoles. Optimization of the metalation conditions for C2 and C6, separately and iteratively, is presented. Using the directed metalation group dance strategy, a late‐stage deuteration of an antipsychotic drug is described. Overall, the controlled migration of the carbamoyl directing group allows multiple functionalization events of the bioactive azaindole scaffold.     

A general modular method of azaindole and thienopyrrole synthesis via Pd-catalyzed tandem couplings of gem-dichloroolefins

A palladium-catalyzed reaction of gem-dichloroolefins and a boronic acid via a tandem intramolecular C-N and intermolecular Suzuki coupling process gave corresponding substituted azaindoles or thienopyrroles. This method is a very modular protocol to synthesize all four isomers of azaindole and two isomers of thienopyrroles in good to excellent yield.     

Carboxylic acids as substrates in homogeneous catalysis

In organic molecules carboxylic acid groups are among the most common functionalities. Activated derivatives of carboxylic acids have long served as versatile connection points in derivatizations and in the construction of carbon frameworks. In more recent years numerous catalytic transformations have been discovered which have made it possible for carboxylic acids to be used as building blocks without the need for additional activation steps. A large number of different product classes have become accessible from this single functionality along multifaceted reaction pathways. The frontispiece illustrates an important reason for this: In the catalytic cycles carbon monoxide gas can be released from acyl metal complexes, and gaseous carbon dioxide from carboxylate complexes, with different organometallic species being formed in each case. Thus, carboxylic acids can be used as synthetic equivalents of acyl, aryl, or alkyl halides, as well as organometallic reagents. This review provides an overview of interesting catalytic transformations of carboxylic acids and a number of derivatives accessible from them in situ. It serves to provide an invitation to complement, refine, and use these new methods in organic synthesis.     

配体参与的有机金属化合物对亚胺的不对称加成反应

手性胺类化合物是一类重要的有机化合物,在生物化学及药物合成中有广泛应用.有机金属化合物对亚胺的不对称加成反应是合成手性胺类化合物的重要方法之一.本文对近年来外加配体参与的有机金属化合物对亚胺的不对称加成反应,特别是催化合成手性胺类化合物的研究进展作一概述.     

Main-chain organometallic polymers: synthetic strategies, applications, and perspectives

Main-chain organometallic polymers utilize transition metal-organic ligand complexes as primary components of their backbones. These hybrid materials effectively integrate the physical and electronic properties of organic polymers with the physical, electronic, optical, and catalytic properties of organometallic complexes. Combined with the rich and continuously growing array of ligands for transition metals, these materials have outstanding potential for use in a broad range of applications. This tutorial review discusses the major classes of main-chain organometallic polymers, including coordination polymers, poly(metal acetylide)s, and poly(metallocene)s. Emphasis is placed on their synthesis, characterization, physical properties, and applications, as well as ongoing challenges and limitations. These discussions are supplemented with highlights from the recent literature. The review concludes with perspectives on the current status of the field, as well as opportunities that lie just beyond its frontier.     

Excited state tautomerization of azaindole

Fluorescent tryptophan analogs, like azatryptophan, offer an advantage for exploring protein and peptide structure and dynamics. The chromophoric moieties, azaindole, of the azatryptophan analogs are investigated for their potential as fluorescent probes. The photophysical properties of 4-azaindole (4AI) and 5-azaindole (5AI) and their tautomers are characterized through computational and experimental methods. Both 4AI and 5AI undergo excited state tautomerization in the presence of 1 M NaOH. The protonated forms of 4AI and 5AI have a fluorescence emission of 415 and 410 nm, respectively, while the tautomers of 4AI and 5AI have a fluorescent emission of 480 and 450 nm, respectively. Gas phase computations (B3LYP/6-31+G**) show that the N1H azaindole tautomer is lower in energy in the ground state by as much as 12.5 kcal mol(-1), while the N(n)H azaindole tautomer is lower in energy in the excited state by as much as 18.1 kcal mol(-1). Solvent effects on the tautomer energy differences were computed using the isodensity polarized continuum model (IPCM). The polarity of the solvent helps to reduce the energy difference between the tautomers in the ground state by as much as 5.8 kcal mol(-1), but not enough to reverse the ground state tautomer preference.     

Organic transformations on sigma-aryl organometallic complexes

This work reviews recent developments in the field of organic transformations on sigma-aryl organometallic complexes. The general notion that M--C sigma bonds are kinetically labile, highly reactive, and incompatible with typical reaction conditions met in organic synthesis has limited the use of these synthetic strategies thus far. However, organic transformations on metal-bound sigma-aryl fragments are being used more and more by chemists in both industry and academia. In this Review, emphasis is put on the synthetic methods applied in this field up to now. The simplicity and generally good yields of these methods are very attractive for the construction of functionalized organometallic building blocks that are potentially useful as photochemical molecular devices, biosensors and -conjugates, or molecular switches. Thus, this Review has been tailored for a broader audience with the aim of encouraging the application of these strategies.     

二茂铁吩开环聚合合成茂金属有机高分子研究进展

综述了近年来二茂铁吩化合物的合成及其开环反应的研究进展,同时总结了聚茂金属有机高分子的性质及其应用。     

New strategies in the synthesis of regioselectively trifluoromethyl- and trifluoromethoxy-substituted arenes as building blocks for biologically active molecules

Regioisomerically pure trifluoromethyl- and trifluoromethoxy-substituted aromatic and heteroaromatic aldehydes and carboxylic acids are valuable building blocks for the synthesis of biologically active molecules. They have been prepared by employing modern organometallic methods. On this basis, a novel access to 2,3-dihydro-5-(trifluoromethoxy)indole was developed which represents an intriguing example of how organometallic and radical chemistry can fecundate each other.     

Ketone Synthesis by Direct,Orthogonal Chemoselective Hydroacylation of Alkenes with Amides: Use of Alkenes as Surrogates of Alkyl Carbanions

Direct functionalization of alkenes and direct transformation of carboxamides are two exciting areas that have attracted considerable attention in recent years. We report herein that secondary amides, the least reactive derivatives of carbonyl compounds, upon activated with triflic anhydride, can serve as effective hydroacylating reagents in partner with alkenes to yield ketones at ambient temperature. The method was applied to the one‐step synthesis of racemic dihydro‐ar‐turmerone. In this method, alkenes serve as surrogates of organometallic reagents, which allows the orthogonal chemoselective reactions. The ready availability of many olefins such as camphene and norbornene permits one‐step ketone synthesis that would require several steps by conventional methods.     

Applications of and alternatives to pi-electron-deficient azine organometallics in metal catalyzed cross-coupling reactions

While the use of pi-deficient azine halides in palladium catalyzed cross-coupling reactions is common, the use of pi-electron deficient azine organometallics has been less intensively examined. In recent years, important advances have been made that are beginning to address this deficiency and need. The purpose of this tutorial review is to highlight and discuss the innovations that facilitate the synthesis of azine-containing biaryls with a focus on the pyridine structural motif. Given the number of important compounds which exhibit azine-heterobiaryls and the wide use of cross-coupling methods in their synthesis, this review should be of interest among synthetic organic chemists and organometallic chemists alike.     

Pincer‐Type Complexes for Catalytic (De)Hydrogenation and Transfer (De)Hydrogenation Reactions: Recent Progress

Pincer complexes are becoming increasingly important for organometallic chemistry and organic synthesis. Since numerous applications for such catalysts have been developed in recent decades, this Minireview covers progress in their use as catalysts for (de)hydrogenation and transfer (de)hydrogenation reactions during the last four years. Aside from noble‐metal‐based pincer complexes, the corresponding base metal complexes are also highlighted and their applications summarized.     

Multi-component syntheses of heterocycles by transition-metal catalysis

For a long time multi-component syntheses of heterocycles have undeniably been a domain of classical carbonyl condensation chemistry. However, the advent of transition-metal catalysis not only has fertilized strategies in heterocyclic synthesis by uni- and bimolecular transformations but the past decade has also witnessed a rapid development of transition-metal catalysis in new multi-component reactions (MCR). Expectedly, palladium catalyzed processes have received a dominant position, yet, other transition-metal complexes are catching up implying organometallic elementary steps that reach even further than cross-coupling and carbometallation. Besides domino MCRs that are purely based upon organometallic catalysis the sequential and consecutive combination with condensation, addition and cycloaddition steps opens a vast playground for the invention of new sequences in heterocyclic synthesis. This tutorial review outlines the underlying reaction based principles of transition-metal catalysis in multi-component syntheses of heterocycles, summarizes recent developments of palladium catalyzed MCR, and highlights the more recent contributions to MCR based heterocyclic synthesis by virtue of rhodium, ruthenium, and copper catalysis.     

有机金属配合物控制的活性自由基聚合研究进展

活性自由基聚合(Living radical polymerization,LRP)是高效可控地制备结构新颖的高分子材料的重要方法,近年来逐渐成为高分子合成领域的研究热点.本文综述了一类重要的活性自由基聚合方法,即有机金属配合物控制的自由基聚合(Organometallic mediated radical polymerization,OMRP)的最新研究进展,介绍了钛、钒、铬、钼、铁、锇、钴、铑、钯和铜等有机金属配合物为催化剂控制的OMRP,并简述了OMRP方法在光致LRP、嵌段共聚物的合成、与其他LRP方法联用及聚合物端基修饰和转化等方面的拓展.此外,本文还对有待进一步深入探索的领域和问题提出了建议和展望.     

Synthesizing optoelectronic heteroaromatic conjugated polymers by cross-coupling reactions

Heteroaromatics-containing polymers comprise a huge class of materials that have received considerable attention due to their interesting electrical, electrochemical, and optical properties. In this review, the recent advances on the use of organometallic cross-coupling reactions for the synthesis of heteroaromatic conjugated polymers for the optoelectronic interests and applications are summarised.     

Cobalt–Pincer Complexes in Catalysis

Non-noble metal catalysts based on pincer type compounds are of special interest for organometallic chemistry and organic synthesis. Next to iron and manganese, currently cobalt–pincer type complexes are successfully applied in various catalytic reactions. In this review the recent progress in (de)hydrogenation, transfer hydrogenation, hydroboration and hydrosilylation as well as dehydrogenative coupling reactions using cobalt–pincer complexes is summarised.     

Charge-tagged ligands: useful tools for immobilising complexes and detecting reaction species during catalysis

In recent years, charge-tagged ligands (CTLs) have become valuable tools in organometallic catalysis. Insertion of an ionic side chain into the molecular skeleton of a known ligand has become a useful protocol for anchoring ligands, and consequently catalysts, in polar and ionic liquid phases. In addition, the insertion of a cationic moiety into a ligand is a powerful tool that can be used to detect reaction intermediates in organometallic catalysis through electrospray ionisation mass spectrometry (ESI-MS) experiments. The insertion of an ionic tag ensures the charge in the intermediates independently of the ESI-MS. For this reason, these ligands have been used as ionic probes in mechanistic studies for several catalytic reactions. Here, we summarise selected examples on the use of CTLs as immobilising agents in organometallic catalysis and as probes for studying mechanisms through ESI-MS.     

Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir,Ru, Rh,Os, Pd,Pt) Complexes as Antimalarial Agents

In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance. The development of organometallic compounds (those containing metal-carbon bonds) as antimalarial drugs has been exemplified by the clinical development of ferroquine in the nascent field of Bioorganometallic Chemistry. With their inherent physicochemical properties, organometallic complexes can modulate the discipline of chemical biology by proffering different modes of action and targeting various enzymes. With the beneficiation of platinum group metals (PGMs) in mind, this review aims to describe recent studies on the antimalarial activity of PGM-based organometallic complexes. This review does not provide an exhaustive coverage of the literature but focusses on recent advances of bioorganometallic antimalarial drug leads, including a brief mention of recent trends comprising interactions with biomolecules such as heme and intracellular catalysis. This resource can be used in parallel with complementary reviews on metal-based complexes tested against malaria.