Direct (Hetero)arylation Reactions of (Hetero)arenes as Tools for the Step- and Atom-Economical Synthesis of Biologically Active Unnatural Compounds Including Pharmaceutical Targets

Abstract

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 Conclusion

Are Vanadium Intermediates Suitable Mimics in Non-Heme Iron Enzymes? An Electronic Structure Analysis

“…Selective C-H activation is essential 1 for the synthesis of bioactive molecules [2][3][4] and natural products [5][6][7][8][9][10][11][12][13] , medicinal chemistry 3,[14][15][16][17] , the materials industry [18][19][20] , and agricultural industry [21][22][23] . Synthetic routes to activate unreactive C-H bonds require harsh conditions 24 and usually show poor selectivity 25 owing to the high C-H bond dissociation energy and its inertness due to low polarity 26 .…”

An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

“…On the other hand, classical Pd-catalysed Suzuki-type reactions have only been used for the preparation of imidazole-pyridine fluorophores 2PBI (336), 3PBI (337), TBPI (338), and MPBI (339) [203]. Instead, atom economic strategies involving Pd-catalysed regioselective direct (hetero)arylation reactions of heteroaromatics with (hetero)aryl halides or pseudohalides [9][10][11][12][13][14][15], which have been and are still frequently used in the chemistry of imidazole derivatives, as well as the van Leusen reaction based of tosylmethylisocyanides, which is one of the most appropriate strategies for the preparation of imidazole-based medicinal molecules [260], to the best of our knowledge, have never been used for the synthesis of hybrids and conjugates belonging to the classes of substances mentioned in this review.…”

“…This review, with 261 references, in which we testified our continuing interest in the synthesis and bioactivity of imidazole derivatives [8][9][10][11][12][13][14][15], aims to summarise and comment on the main results obtained from the end of 1900s until the end of February 2020 in studies conducted by numerous international research groups on the synthesis and evaluation of the antibacterial properties of imidazole-based molecular hybrids and conjugates in which their discrete functional elements are directly covalently linked or are connected through a linker or spacer. The review, in which significant attention was paid to summarise the strategies used to overcome the antibiotic resistance of pathogens whose infections are difficult to treat with conventional antibiotics, was organised in the following main sections: However, this review did not include the synthesis and evaluation of the bioactivity of molecular hybrids and conjugates in which imidazole moieties are fused with carbo-or hetero-cyclic subunits or contain only (un)functionalised acyclic groups.…”

Manganese-Porphyrin-Catalyzed C-H Fluorination: Hydrocarbons, But Not Drugs?

“…Selective C-H functionalization plays an important role 3 in the synthesis of bioactive natural products [4][5][6][7][8][9][10][11][12][13][14] , drug metabolism [15][16] , pharmaceutical industry [17][18][19][20][21][22][23] , DNA repair [24][25][26][27] , and transcription [28][29][30] . C-H bonds can be functionalized in various ways, including but not limited to cyanation [31][32][33][34][35][36][37][38] , oxidation 39 , hydroxylation 40 , epoxidation [41][42] , and halogenation [43][44][45] .…”