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A selective direct arylation of the different Csp2‐H bonds of imidazo[2,1‐b]thiazole with (hetero) aryl halides can be achieved simply by switching from a palladium catalyst system to the use of stoichiometric amounts of copper. The observed selectivity, also rationalized by DFT calculations, can be explained by a change in the mechanistic pathways between electrophilic palladation and base‐promoted C−H metalation. [ABSTRACT FROM AUTHOR]

The palladium-catalyzed direct arylation of azoles with (hetero)aryl halides is nowadays one of the most versatile and efficient procedures for the selective synthesis of heterobiaryls. Although this procedure is, due to its characteristics, also of great interest in the industrial field, the wide use of a reaction medium such as DMF or DMA, two polar aprotic solvents coded as dangerous according to environmental, health, safety (EHS) parameters, strongly limits its actual use. In contrast, the use of aromatic solvents as the reaction medium for direct arylations, although some of them show good EHS values, is poorly reported, probably due to their low solvent power against reagents and their potential involvement in undesired side reactions. In this paper we report an unprecedented selective C-5 arylation procedure involving anisole as an EHS green reaction solvent. In addition, the beneficial role of benzoic acid as an additive was also highlighted, a role that had never been previously described. [ABSTRACT FROM AUTHOR]

Two methods for the one-pot synthesis of 2,5-diarylimidazoles by palladium-catalyzed direct C--H arylation of 1-substituted imidazoles with aryl bromides have been devised. The first method, promoted by copper(I) iodide, is best suited for electron-poor aryl bromides, and also allows the 2,5-diarylation of thiazole and oxazole. The use of xylene instead of DMA is the key for the efficiency of the second method, which gives the best results with electron-rich aryl bromides. [ABSTRACT FROM AUTHOR]

The significant number of papers and reviews published in this last decade testifies to the utility of the transition-metal-catalyzed direct C-H (hetero)arylation reactions of (hetero)arenes as efficient and powerful tools for the step- and atom-economical, regio- and chemoselective synthesis of natural and unnatural compounds. However, no review has so far been devoted to summarizing the application of these reactions in the synthesis of biologically active compounds. This review with 341 references aims to fill this gap, providing a comprehensive picture of the transition-metal-catalyzed intra- and intermolecular direct C-H (hetero)arylation reactions of (hetero)arenes with (hetero)aryl halides or pseudohalides that have been used as key steps of syntheses of unnatural biologically relevant compounds including pharmaceutical targets, up to the end of September 2015. Attention has also been directed to provide a brief description of the biological properties of the synthesized compounds. 1 Introduction 2 Syntheses via Intramolecular Direct (Hetero)arylation of (Hetero) arene Derivatives 3 Syntheses via Intermolecular Direct (Hetero)arylation Reactions 3.1 Of Arenes 3.2 Of Five-Membered Heteroarenes with One Heteroatom 3.3 Of Five-Membered Heteroarenes with Two Heteroatoms 3.4 Of Five-Membered Heteroarenes with Three and Four Heteroatoms 3.5 Of Five-Membered Heteroarenes Fused to a Six-Membered Heteroarene 3.6 Of Five-Membered Heteroarene Moieties of Tricyclic Heteroarenes 3.7 Of Six-Membered Heteroarenes 4 Syntheses of Nitrogen-Containing Polycyclic Heteroarene via One-Pot Palladium-Catalyzed Domino Direct Arylation/N-Arylation Reactions 5 Conclusions [ABSTRACT FROM AUTHOR]

In recent years, environmental and economic reasons have motivated the development of transition metal-free carbon-carbon bond forming reactions and some excellent reviews have covered this research area of particular interest for the pharmaceutical industry. However, none of these reviews has been specifically dedicated to summarize and discuss the results achieved in the rapidly growing field of the transition metal-free direct (hetero)arylation reactions of heteroarenes. This review, which covers the literature from 2008 to 2014, aims to provide a thorough insight into the synthetic and mechanistic aspects of these atom economic and environmentally benign reactions also highlighting their advantages and possible disadvantages compared to conventional methods for the synthesis of arylheteroarenes and biheteroaryls via transition metal-catalyzed reactions. [ABSTRACT FROM AUTHOR]

This review with 387 references covers the literature until the end of November 2013 on the synthesis of multiply arylated heteroarenes via highly selective palladium-catalyzed direct C-H arylation reactions of heteroarene derivatives with aryl halides or pseudohalides or aryliodonium salts. Particular attention has been made to describe the synthesis of biologically active compounds and substances that are privileged structural motifs in organic materials. The practicality, versatility, and limitations of the various developed arylation protocols are discussed. 1 Introduction 2 Synthesis of Multiply Arylated Five-Membered Hetero­arenes with One Heteroatom 2.1 Multiply Arylated Furan and Benzo[b]furan Derivatives 2.2 Multiply Arylated Thiophenes and Benzo[b]thiophene Derivatives 2.3 Multiply Arylated Pyrrole and Indole Derivatives 3 Synthesis of Multiply Arylated Five-Membered Hetero­arenes with Two or More Heteroatoms 3.1 Multiply Arylated Pyrazole and 2H-Indazole Derivatives 3.2 Multiply Arylated Isoxazole Derivatives 3.3 Multiply Arylated Oxazole Derivatives 3.4 Multiply Arylated Thiazole and Thiazole N-Oxide Derivatives 3.5 Multiply Arylated Imidazole and Imidazole N-Oxide Derivatives­ 3.6 Multiply Arylated 1,2,3-Triazole and 1,2,3-Triazole N-Oxide Derivatives 3.7 Diarylated 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives 3.8 Diarylated Sydnone, 2,1,3-Benzothiadiazole, and Tetrazole Derivatives 4 Synthesis of Multiply Arylated Six-Membered Hetero­arenes 4.1 Diarylated Pyridines, Pyridine N-Oxides, and Pyrazine N-Oxides 5 Synthesis of Multiply Arylated Compounds Formed by Five-Membered Heteroarenes Fused to Five-Membered Heteroarenes 5.1 Diarylated Thieno[2,3-b]thiophenes, Imidazo[1,2-b]pyrazoles, and Thiazolo[3,2-b]-1,2,4-triazoles 6 Synthesis of Multiply Arylated Compounds Formed by Six-Membered Heteroarenes Fused to Five-Membered Hetero­arenes 6.1 Diarylated Indolizines, Pyrimido[5,4-b]indolizines, Pyrrolo[2,3-b]pyridines, Pyrazolo[1,5-a]pyrimidines, Imidazo[1,2-a]pyridines, Imidazo[1,5-a]pyridines, Xanthines, Imidazo[1,2-b]tetrazines, Imidazo[1,2-a]pyrazines, and ­Furo[3,2-b]pyridines 7 Conclusions [ABSTRACT FROM AUTHOR]

A series of 1,4-phenylene-spaced bis-imidazoles with fluorescence quantum yields up to 0.90 and large Stokes shifts have been designed and synthesized using recently developed regioselective direct CH arylation protocols. All the fluorophores show a bright blue-green emission that is well retained in the solid state. DFT calculations attributed their excellent luminescence properties to the significant planarization of the molecules in the equilibrium structures of their excited electronic states. [ABSTRACT FROM AUTHOR]

In recent years, transition metal-catalyzed direct (hetero)arylation reactions of heteroarenes with (hetero)aryl halides and pseudohalides have received significant attention as eco-friendly and economic alternatives to classical methods for the construction of heteroaryl-(hetero)aryl CC bonds by transition metal-catalyzed cross-couplings involving the use of stoichiometric amounts of organometallic reagents. This critical review with 430 references covers the results obtained in the period January 2009 to February 2013 in the area of the transition metal-catalyzed direct inter- and intramolecular (hetero)arylation reactions of heteroarenes containing one heteroatom. Particular attention has been given to illustrate chemo- and site selectivity aspects of these reactions as well applications of these CC bond forming reactions in the synthesis of pharmaceutically relevant compounds, natural products and their analogues and precursors. The most recent advancements into the mechanism(s) of these reactions have also been briefly reported. [ABSTRACT FROM AUTHOR]

The palladium/copper cocatalyzed sila-Sonogashira re-action of (hetero)arylethynysilanes with (hetero)aryl bromides in toluene and water at 40 °C under PTC conditions gave the required di(hetero)arylethynes in moderate to high yields. Activated, deactivated and orito-substituted (hetero)aryl bromides are well tolerated. This protocol also allowed the preparation of symmetrical diarylethynes by double arylation of 1,2-bis(trimethylsilyl)ethyne. [ABSTRACT FROM AUTHOR]

Review: [175 refs. [ABSTRACT FROM AUTHOR]

A simple and efficient method to prepare several 5-arylated azoles is presented. [ABSTRACT FROM AUTHOR]

Novel trans-restricted analogues of resveratrol in which the C–C double bond of the natural derivative has been replaced by diaryl substituted imidazole analogues have been designed. The syntheses of 1,4-, 2,4-, and 2,5-diarylimidazoles, in which the two aryl moieties are linked to the heteroaromatic core in a 1,3 fashion in order to preserve the trans stereochemistry, have been successfully carried out by regioselective sequential transition metal-catalyzed arylations of simple, commercially available imidazole precursors. The anticancer activity of selected analogues has been evaluated in vitro against the NCI-60 human tumor cell lines panel. From this screening, we were able to select a synthetic candidate that resulted more active than its natural lead. [ABSTRACT FROM AUTHOR]