Ruzal Sitdikov

The advancement of sustainable synthetic methodologies is a central goal of modern chemistry, given the societal importance of green chemical practices. Amide groups and halogen atoms are prevalent in chemical and biological systems, with major relevance to both organic and medicinal chemistry. Consequently, there is strong demand for efficient methods that enable amide bond formation and selective halogenation under mild, resource‐efficient conditions. Conventional approaches typically require separate steps, activating reagents, catalysts, or harsh reaction conditions, which limit scalability and sustainability. To address these challenges, we developed a novel electrochemical cascade methodology that unites amide bond formation and electro‐induced C─H halogenation in a single, atom‐economical, and environmentally benign process. This strategy provides streamlined access to halogenated N ‐aryl amides, carbamates, and ureas without additives or co‐reagents. The method's generality and robustness are demonstrated across more than 145 examples, encompassing complex, functional group‐dense scaffolds and pharmaceutically relevant compounds, including successful scale‐up reactions.

The advancement of sustainable synthetic methodologies is a central goal of modern chemistry, given the societal importance of green chemical practices. Amide groups and halogen atoms are prevalent in chemical and biological systems, with major relevance to both organic and medicinal chemistry. Consequently, there is strong demand for efficient methods that enable amide bond formation and selective halogenation under mild, resource‐efficient conditions. Conventional approaches typically require separate steps, activating reagents, catalysts, or harsh reaction conditions, which limit scalability and sustainability. To address these challenges, we developed a novel electrochemical cascade methodology that unites amide bond formation and electro‐induced C─H halogenation in a single, atom‐economical, and environmentally benign process. This strategy provides streamlined access to halogenated N ‐aryl amides, carbamates, and ureas without additives or co‐reagents. The method's generality and robustness are demonstrated across more than 145 examples, encompassing complex, functional group‐dense scaffolds and pharmaceutically relevant compounds, including successful scale‐up reactions.

Herein, we report a mild and efficient cobalt-catalyzed electrochemical method for the regioselective C–H acyloxylation of aromatic and vinylic amides, utilizing 8-aminoquinoline as the directing group. Notably, this protocol requires no stoichiometric oxidants and operates at room temperature in an undivided cell setup, providing sustainable access to a diverse set of ortho-acyloxylated products with broad functional group tolerance.

Herein, a mild and efficient cobalt-catalyzed electrochemical method for the C–H acyloxylation of aromatic and vinylic amides is reported. The 8-aminoquinoline directing group facilitates selective (ortho-)acyloxylation under electrochemical conditions at room temperature without the need for additional redox reagents. This sustainable protocol exhibits broad functional group tolerance and provides access to a wide range of acyloxylated amide derivatives using readily available carboxylic acids. The electrochemical approach avoids stoichiometric oxidants, generating only hydrogen as the byproduct, and thus offers a valuable alternative to traditional C–H functionalization strategies.

Considering the significant future benefits of widespread sustainable chemical practices, the development of green synthetic methodologies remains a critical objective in modern chemistry. Amide groups and halogen atoms are ubiquitous in chemical and biological systems, with their structural and pharmacological significance enabling multiple applications in the fields of organic and medicinal chemistry. As a result, there is currently a major demand for methods that allow for the efficient construction of amide bonds and selective halogenation under environmentally friendly conditions. Existing approaches typically require distinct methods for amide bond formation and halogenation, often relying on activating reagents or catalysts, complex reaction conditions, and additives, which can hinder scalability and accessibility. With the aim of addressing these shortcomings of existing strategies, we report an electrochemical cascade methodology that enables the atom-economical and environmentally benign synthesis of halogenated N-aryl amide, carbamate and urea derivatives, which proceeds via amide bond formation followed by electrocatalytic C-H chlorination. The robustness of this method is demonstrated through the synthesis of over 180 such products, encompassing a wide range of functional groups and complex molecular scaffolds, and including many pharmaceutically relevant compounds and several scale-up examples.

With the resurgence of electrosynthesis in organic chemistry, there is a significant increase in the number of routes available for late-stage functionalization (LSF) of drugs. Electrosynthetic methods, which obviate the need for hazardous chemical oxidants or reductants, offer unprecedented control of reactions through the continuous variation of the applied potential and the possibility of combination with photochemical processes. This capability is a substantial advantage for performing electrochemical or photoelectrochemical LSF. Ultimately, these protocols are poised to become a vital component of the medicinal chemist's toolkit. In this review, we discuss electrochemical protocols that have been demonstrated to be applicable for the LSF of pharmaceutical drugs, their derivatives, and natural substrates. We present and analyze representative examples to illustrate the potential of electrochemistry or photoelectrochemistry for the LSF of valuable molecular scaffolds.

Chloroarenes constitute fundamental building blocks in organic synthesis and are widely applied in the synthesis of bioactive compounds, fine chemicals, materials, natural products and pharmaceuticals. Electrochemical chlorination has been recognized as a promising synthetic method for accessing chloroarenes, but it has proved challenging to achieve in practice as shown by the limited number of existing protocols. Herein, we report on a highly general electrocatalytic strategy for the regioselective chlorination of various substituted heteroaryl scaffolds in an undivided cell setup, using ethyl chloroformate as the chlorine source. This strategy offers several practical advantages over existing methodologies, including an operationally simple experimental setup, exceptional functional group tolerance, and the possibility to form either the mono- or bis-chlorinated products in high selectivity depending on the choice of catalyst loading, electric current and ethyl chloroformate equivalents. The practicality and selectivity of the protocol were demonstrated by the successful chlorination of an array of densely-substituted arene frameworks as well as by the synthesis of chlorinated bioactive molecules.

A new nickel-catalyzed electrochemical, reductive cross-coupling for the trideuteromethylation of alkyl and aryl bromides is reported in which CD₃ arenesulfonate derivatives were used as effective and readily available CD₃ sources. The CD₃-labeled products were obtained with good yields. It was demonstrated that this methodology is scalable and can be efficiently used for various methylations, including ¹³CH₃ and ¹³CD₃ labeling. Received: 20 November 2023 Accepted after revision: 22 January 2024 Article published online: 04 March 2024 © 2024. Thieme. All rights reserved Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Novel electrochemical aptasensors based on glassy carbon electrodes modified with electropolymerized Neutral red and polycarboxylated macrocyclic ligands onto which the DNA aptamers were covalently attached have been developed for detection of Aflatoxin B1 (AFB1). The interaction with an analyte resulted in the decrease of the cathodic peak current of the probe measured by CV and in the increase of the electron transfer resistance determined by EIS. The limit of detection was found to be 0.1 nM for CV and 0.05 nM for EIS methods, respectively. The aptasensor makes it possible to detect AFB1 in peanuts, cashew nuts, white wine and soy sauce with a recovery of 85–100 %.