The selective installation of azide groups into C­(sp3)–H bonds is a priority research topic in organic synthesis, particularly in pharmaceutical discovery and late-stage diversification. Herein, we demonstrate a generalized manganese-catalyzed oxidative azidation methodology of C­(sp3)–H bonds using nucleophilic NaN3 as an azide source under electrophotocatalytic conditions. This approach allows us to perform the reaction without the necessity of adding an excess of the substrate and successfully avoiding the use of stoichiometric chemical oxidants such as iodine­(III) reagent or NFSI. A series of tertiary and secondary benzylic C­(sp3)–H, aliphatic C­(sp3)–H, and drug-molecule-based C­(sp3)–H bonds in substrates are well tolerated under our protocol. The simultaneous gram-scale synthesis and the ease of transformation of azide to amine collectively advocate for the potential application in the preparative synthesis. Good reactivity of the tertiary benzylic C­(sp3)–H bond and selectivity of the tertiary aliphatic C­(sp3)–H bond in substrates to incorporate nitrogen-based functionality at the tertiary alkyl group also provide opportunities to manipulate numerous potential medicinal candidates. We anticipate our synthetic protocol, consisting of metal catalysis, electrochemistry, and photochemistry, would provide a new sustainable option to execute challenging organic synthetic transformations.

Benzo­[4,5]­imidazo­[2,1-a]­isoquinolin-6­(5H)-one derivatives are prevalent in many synthetic intermediates, pharmaceuticals, and organic materials. Herein, we develop a Mn-catalyzed electrochemical radical cascade cyclization reaction that uses electricity as the primary energy input to promote the reaction, leading to a series of benzo­[4,5]­imidazo­[2,1-a]­isoquinolin-6­(5H)-one derivatives under exogenous-oxidant-free conditions. It is worth noting that this electrochemical method can not only realize the synthesis of benzo­[4,5]­imidazo­[2,1-a]­isoquinolin-6­(5H)-one derivatives but also provides a new strategy for generating alkyl radicals from alkylboronic acids.

The cross-coupling of C­(sp3)–H and N–H represents one of the most straightforward approaches to construct saturated nitrogen-containing compounds. The additional oxidants or halogenated reagents are generally required in such processes. Herein, we developed an electrochemical oxidative intramolecular C­(sp3)–H amination of amides by employing a carbon rod anode and a platinum plate cathode in an undivided cell under constant-current electrolysis conditions. Tetrabutylammonium acetate was not only employed as an electrolyte, but also can form the intermolecular hydrogen bond with amide and promote cleavage of the N–H bond. The additional oxidants and N-halogenation step can be obviated in this methodology. A variety of benzylic and nonactivated tertiary, secondary, primary C­(sp3)–H amination can be achieved with good yields.

Considering that stoichiometric borane and oxidant are required in the classical alkene anti-Markovnikov hydration process, it remains appealing to achieve the transformation in a catalytic protocol. Herein, a visible-lightmediated anti-Markovnikov addition of water to alkenes by using an organic photoredox catalyst in conjunction with a redox-active hydrogen atom donor was developed, which avoided the need for a transition-metal catalyst, stoichiometric borane, as well as oxidant. Both terminal and internal olefins are readily accommodated in this transformation to obtain corresponding primary and secondary alcohols in good yields with single regioselectivity. This procedure can be scaled up to gram scale with a 230 turnover number based on photocatalyst.

Deuterated compounds are valuable in synthetic, pharmaceutical and analytical chemistry. The deuteration of halides is a widespread method for its good site-selectivity. However, the facile, efficient and economical deuterium incorporation still remains a big challenge. In this work, we introduced a practical deuteration of (hetero)arylhalides through electrochemical reduction method. This transformation proceeded smoothly under room temperature without metal catalysts, external-reductants, toxic or dangerous reagents. Remarkably, low-cost and chemical equivalent D 2 O was the sole deuterium source in this reaction. The professional electrosynthesis equipment was not essential, but common batteries and electrodes were enough.