Electrochemically selective double C(sp2)-X (X = S/Se, N) bond formation of isocyanides.

The construction of C(sp2)-X (X = B, N, O, Si, P, S, Se, etc.) bonds has drawn growing attention since heteroatomic compounds play a prominent role from biological to pharmaceutical sciences. The current study demonstrates the C(sp2)-S/Se and C(sp2)-N bond formation of one carbon of isocyanides with thiophenols or disulfides or diselenides and azazoles simultaneously. The reported findings could provide access to novel multiple isothioureas, especially hitherto rarely reported selenoureas. The protocol showed good atom-economy and step-economy with only hydrogen evolution and theoretical calculations accounted for the stereoselectivity of the products. Importantly, the electrochemical reaction could exclusively occur at the isocyano part regardless of the presence of susceptible radical acceptors, such as a broad range of arenes and alkynyl moieties, even alkenyl moieties.

Electrochemical Oxidative Carbon-Atom Difunctionalization: Towards Multisubstituted Imino Sulfide Ethers.

Ethers (C-O/S) are ubiquitously found in a wide array of functional molecules and natural products. Nonetheless, the synthesis of imino sulfide ethers, containing an N(sp2 )=C(sp2 )-O/S fragment, still remains a challenge because of its sensitivity to acid. Developed here in is an unprecedented electrochemical oxidative carbon-atom difunctionalization of isocyanides, providing a series of novel multisubstituted imino sulfide ethers. Under metal-free and external oxidant-free conditions, isocyanides react smoothly with simple and readily available mercaptans and alcohols. Importantly, the procedure exhibited high stereoselectivities, excellent functional-group tolerance, and good efficiency on large-scale synthesis, as well as further derivatization of the products.

Manganese-Catalyzed Oxidative Azidation of C(sp3)-H Bonds under Electrophotocatalytic Conditions.

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.

Oxidant-Induced Azolation of Electron-Rich Phenol Derivatives.

Since N-arylazoles are widely present in natural products, pharmaceuticals, and functional materials, it is important to develop a simple and efficient synthetic method for the synthesis of N-arylazoles. Herein, an oxidant-induced intermolecular azolation of phenol derivatives was demonstrated under catalyst-free condition. Both monoazolation and diazolation of phenols can be successfully achieved via this practical and powerful method.

Electrochemical oxidative decarboxylation and 1,2-aryl migration towards the synthesis of 1,2-diaryl ethers.

Carboxylic acid compounds are important chemicals and are widely present in various natural products. They are not only nucleophiles, but also radical precursors. Classic transition-metal-catalyzed and photochemical decarboxylation have shown their excellent site selectivity in radical chemistry. However, electrochemical decarboxylation with a long history hasn't got enough attention in recent years. In this work, the electrochemical oxidative decarboxylation and 1,2-aryl migration of 3,3-diarylpropionic acids have been introduced to construct C-O bonds with alcohols. Remarkably, this transformation can proceed smoothly without metal catalysts and external oxidants.

Catalyst-free electrochemical decarboxylative cross-coupling of N-hydroxyphthalimide esters and N-heteroarenes towards C(sp3)-C(sp2) bond formation.

Cheap and widely available carboxylic acids are a class of ideal substrates to construct valuable compounds. As a candidate of decarboxylative reactions, the acid-based neutral N-hydroxyphthalimide ester undergoes a reductive decarboxylative process rather than a common oxidative decarboxylative process, which is a potential transformation mode for new reactions. In this work, we developed an electrochemical C(sp3)-C(sp2) coupling of N-hydroxyphthalimide esters and N-heteroarenes without any catalysts. Remarkably, this electrochemical protocol can not only be directly realised by carboxylic acids in a one-pot fashion, but also be scaled up using a continuous-flow reactor.

Photoinduced oxidative activation of electron-rich arenes: alkenylation with H2 evolution under external oxidant-free conditions.

The dehydrogenative cross-coupling of arenes and alkenes is a particularly ideal approach for the synthesis of aryl alkenes. Herein, we report a photo-induced C-H/C-H cross-coupling between electron-rich arenes and styrene derivatives using a dual catalytic system containing an acridinium photosensitizer and a cobaloxime proton-reducing catalyst. This catalytic system enables the Csp2-Csp2 bond formation accompanying H2 evolution. Various substituted aryl alkenes can be afforded with good to excellent yields and high ß-regioselectivity.

Selective Oxidative [4+2] Imine/Alkene Annulation with H2 Liberation Induced by Photo-Oxidation.

The oxidative [4+2] annulation reaction represents an elegant and versatile synthetic protocol for the construction of six-membered heterocyclic compounds. Herein, a photoinduced oxidative [4+2] annulation of NH imines and alkenes was developed by utilizing a dual photoredox/cobaloxime catalytic system. Various multisubstituted 3,4-dihydroisoquinolines can be obtained in good yields. This method is not only obviated the need of stiochiometric amounts of oxidants but also exhibited excellent atom economy by generating H2 as the only byproduct. Remarkably, high regioselectivity and trans diastereoselectivity can be achieved in this transformation even if the Z/E mixture of alkenes were employed.