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The late‐stage functionalization of active pharmaceutical ingredients is a key challenge in medicinal chemistry. Furthermore, N‐aryl triazoles and tetrazoles are important structural motifs with the potential to boost the activity of diverse drug molecules. Using easily accessible dibenzothiophenium salts for the ruthenium‐catalyzed C−H arylation, these scaffolds were introduced into a variety of bioactive compounds. Our methodology uses cost‐efficient ruthenium, KOAc as a mild base and gives access to a plethora of highly decorated triazole and tetrazole containing drug derivatives. [ABSTRACT FROM AUTHOR]

This article discusses a study on the late-stage functionalization of pharmaceutical drugs using ruthenium-catalyzed C-H activation. The researchers focused on introducing N-Aryltriazoles and Tetrazoles into drug molecules, as these structures have the potential to enhance their activity. The method described in the article utilizes accessible dibenzothiophenium salts for the C-H arylation, allowing for the incorporation of these motifs into various bioactive compounds. The study demonstrates that the method is cost-effective, efficient, and compatible with complex dibenzothiophenium salts derived from pharmaceuticals and natural products. Mechanistic studies were conducted to understand the reaction mechanism, and the researchers proposed a catalytic cycle involving the formation of an active catalytic species. Overall, this study provides a mild and versatile method for the synthesis of medicinally relevant compounds. [Extracted from the article]

Indole derivatives are fundamental structural units in many bioactive compounds and molecular materials. The site‐selective C7‐functionalization of these moieties has been proven to be extremely challenging due to the inherent reactivity of the C2‐ and C3‐positions. Herein, we report the first electro‐C7‐alkenylation of indoles. This novel and sustainable methodology provides highly exclusive access to the C7‐position devoid of often toxic and expensive chemical oxidants. Moreover, an array of substrates was successfully alkenylated at the C7‐position, and versatile product diversification was achieved. [ABSTRACT FROM AUTHOR]

Distal C(sp2)−H and C(sp3)−H functionalizations have recently emerged as step‐economical tools for molecular synthesis. However, while the C(sp2)−C(sp3) construction is of fundamental importance, its formation through double remote C(sp2)−H/C(sp3)−H activation has proven elusive. By merging the ruthenium‐catalyzed meta‐C(sp2)−H functionalization with an aliphatic hydrogen atom transfer (HAT) process, we, herein, describe the catalyzed twofold remote C(sp2)−H/C(sp3)−H functionalizations via photo‐induced ruthenium‐mediated radical relay. Thus, meta‐C(sp2)−H arene bonds and remote C(sp3)−H alkane bonds were activated by a single catalyst in a single operation. This process was accomplished at room temperature by visible light—notably without exogenous photocatalysts. Experimental and computational theory studies uncovered a manifold comprising ortho‐C−H activation, single‐electron‐transfer (SET), 1,n‐HAT (n=5–7) and σ‐activation by means of a single ruthenium(II) catalyst. [ABSTRACT FROM AUTHOR]

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Distal C(sp 2 )-H and C(sp 3 )-H functionalizations have recently emerged as step-economical tools for molecular synthesis. However, while the C(sp 2 )-C(sp 3 ) construction is of fundamental importance, its formation through double remote C(sp 2 )-H/C(sp 3 )-H activation has proven elusive. By merging the ruthenium-catalyzed meta-C(sp 2 )-H functionalization with an aliphatic hydrogen atom transfer (HAT) process, we, herein, describe the catalyzed twofold remote C(sp 2 )-H/C(sp 3 )-H functionalizations via photo-induced ruthenium-mediated radical relay. Thus, meta-C(sp 2 )-H arene bonds and remote C(sp 3 )-H alkane bonds were activated by a single catalyst in a single operation. This process was accomplished at room temperature by visible light-notably without exogenous photocatalysts. Experimental and computational theory studies uncovered a manifold comprising ortho-C-H activation, single-electron-transfer (SET), 1,n-HAT (n=5-7) and σ-activation by means of a single ruthenium(II) catalyst., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The ruthenium-catalyzed synthesis of diarylmethane compounds was realized under exceedingly mild photoredox conditions without the use of exogenous photocatalysts. The versatility and robustness of the ruthenium-catalyzed C-H benzylation was reflected by an ample scope, including multifold C-H functionalizations, as well as transformable pyrazoles, imidates and sensitive nucleosides. Mechanistic studies were indicative of a photoactive cyclometalated ruthenium complex, which also enabled versatile C-H allylations., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Ambient temperature ruthenium-catalyzed C-H arylations were accomplished by visible light without additional photocatalysts. The robustness of the ruthenium-catalyzed C-H functionalization protocol was reflected by a broad range of sensitive functional groups and synthetically useful pyrazoles, triazoles and sensitive nucleosides and nucleotides, as well as multifold C-H functionalizations. Biscyclometalated ruthenium complexes were identified as the key intermediates in the photoredox ruthenium catalysis by detailed computational and experimental mechanistic analysis. Calculations suggested that the in situ formed photoactive ruthenium species preferably underwent an inner-sphere electron transfer., (© 2020 The Authors. Published by Wiley-VCH GmbH.)