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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]

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]

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]

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]