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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]

Tetrasubstituted 1H-imidazoles are a large family of heteroarene derivatives that are known to include natural products isolated from marine sponges and synthetic compounds possessing a broad range of biological and pharmacological properties. Consequently, a great deal of attention has been given to the synthesis of these heteroarenes and reviews covering some synthetic aspects of this topic have been published in recent years. However, none of these reviews provides a comprehensive overview of the catalytic methods developed in the literature for the preparation of this important class of heteroarenes. This article aims to provide an updated critical picture of the catalytic processes reported in the literature up to the end of 2017 for the synthesis of 1,2,4,5-tetrasubstituted 1H-imidazoles illustrating these protocols and their characteristic features such as scope, efficiency, versatility, and limitations. The review also summarizes the mechanisms proposed for many of the reported processes. [ABSTRACT FROM AUTHOR]

An efficient synthesis of symmetrical 1,2-disubstituted 4,5- dialkynylimidazoles by Sonogashira alkynylation of the corresponding 4,5-dibromo derivatives was developed. Moreover, through a careful tuning of the palladium ligand, unsymmetrical 1,2-disusbtituted 4,5-dialkynylimidazoles were also prepared through a regioselective C5 alkynylation of 4,5-dibromoimidazoles, followed by a second alkynylation involving the 4-bromo derivatives so obtained. This interesting class of imidazole-fused enediynes is also able to give thermal Bergman cycloaromatization (BC), as proved by DSC experiments. [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]

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 variety of 2-substituted 5-alkynyl-1 H -imidazoles were easily prepared by a one-pot sequential procedure involving a highly regioselective electrophilic C-5 bromination of 1,2-dimethyl-1 H -imidazole, 2-chloro-1-methyl-1 H -imidazole, and 2-aryl-1-methyl-1 H- imidazoles, followed by an efficient palladium/copper co-catalyzed Sonogashira-type alkynylation. [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]