Electrochemical selective divergent C-H chalcogenocyanation of N-heterocyclic scaffolds.

An electrochemical direct selective C-H chalcogenocyanation approach for indolizine derivatives under mild conditions has been described. Cyclic enone-fused, chromone-fused and 2-substituted indolizines possessing EDGs (electron donating groups) and EWGs (electron withdrawing groups) were successfully reacted with NH4SCN and KSeCN under electrochemical conditions to provide a wide array of mono and bis-chalcogenocyanate-indolizines in 75-94% yields. In addition, 1-substituted imidazo[1,5-a]quinolines were also successfully chalcogenocyanated under the optimized reaction conditions providing a platform for the synthesis of pharmaceutically privileged molecules. By switching the reaction conditions, the developed protocol offers selective synthesis of C-3 thiocyanate and 1,3 bis-thiocyanate indolizines in good to excellent yields under catalyst-free conditions. On the basis of control experiments and cyclic voltammetry data, a plausible reaction pathway is also presented.

Electrochemical, Regioselective, and Stereoselective Synthesis of Allylic Thioethers and Selenoethers under Transition-Metal-Free and Oxidant-Free Conditions.

We disclose a mild, scalable, electricity-promoted cross coupling protocol between allylic iodides and disulfides/diselenides for the formation of C-S/Se bonds in the absence of transition metals, bases, and oxidants. The stereochemically different densely functionalized allylic iodides gave regio- and stereoselective diverse thioethers in good yields. This strategy demonstrates a sustainable promising approach for the synthesis of allylic thioethers in 38-80% yields. This protocol also provides a synthetic platform for the synthesis of allylic selenoethers. A single-electron transfer radical pathway was also validated with radical scavenger experiments and cyclic voltammetry data.

Palladium-catalyzed synthesis of 2,3-disubstituted indoles via arylation of ortho-alkynylanilines with arylsiloxanes.

In this study, we report the electrophilic cyclization of N,N-dimethyl-o-alkynylanilines with arylsiloxanes in the presence of [Pd(OAc)2] and Ag2O catalytic system, which leads to the efficient synthesis of indoles, similar to the one that is obtained through Larock indole synthesis. A range of aryl(trimethoxy)silanes with EDGs and EWGs were successfully utilized for the synthesis of a diverse variety of substituted indoles via the cleavage of the C-Si bond. This protocol exhibits good functional group tolerance and wide substrate scope to provide 2,3-diaryl-N-methylindoles in 26-88% yields.

Electrochemical direct C-H mono and bis-chalcogenation of indolizine frameworks under oxidant-free conditions.

Herein, we disclosed a sustainable electrochemical approach for site-selective C-H mono and bis-chalcogenation (sulfenylation or selenylation) of indolizine frameworks. Diversely functionalized disulfides and diselenides possessing EDGs and EWGs were successfully reacted with a variety of indolizines to directly access sulfenylated/selenylated indolizines in 40-96% yields. A mechanistic radical pathway was also validated with control experiments and cyclic voltammogram data.

Base-mediated chalcogenoaminative annulation of 2-alkynylanilines for direct access to 3-sulfenyl/selenyl-1H-indoles.

An efficient and transition metal-free synthesis of 3-sulfenyl/selenyl-1H-indoles via a base-assisted chalcogenoaminative annulation of 2-alkynyl aniline with disulfides/diselenides is described. A series of 2-alkynylanilines were found compatible with dichalcogenides in this transformation providing 3-sulfenyl/selenyl-1H-indoles in good to excellent yields. The presented methodology has the advantages of easily available raw materials, functional group tolerance, and a wide range of substrates that provide access to 3-sulfenylindoles and 3-selenylindoles.

Electrochemical Bisarylation of Carbonyls: A Direct Synthetic Strategy for Bis(indolyl)methane.

An interesting electrochemical direct bisarylation of carbonyls with indole derivatives to afford the corresponding bis(indolyl)methane (BIM) derivatives is described. The developed protocol is suitable for aliphatic, aromatic, and heteroaromatic aldehydes, which react with various electron-rich and electron-poor indoles to afford the corresponding BIMs in good to excellent yields. Isatin derivatives also underwent bisarylation with various indole derivatives under the influence of current to afford the corresponding BIMs in excellent yields.

Highly atom-economical, catalyst-free, and solvent-free phosphorylation of chalcogenides.

Silica gel promoted, catalyst-free and solvent-free S-P, Se-P and Te-P bond formations are described. A variety of disulfides coupled with diarylphosphine oxides provide the corresponding phosphinothioates in excellent yields. For the first time, diselenides and ditellurides reacted with dialkyl phosphites under catalyst-free conditions to provide the corresponding phosphoroselenoates and phosphorotelluroates, respectively, in good to excellent yields.

Ketones as electrophiles in two component Baylis-Hillman reaction: a facile one-pot synthesis of substituted indolizines.

2-Alkanoyl(aroyl)-pyridines have been successfully used for coupling with alkyl vinyl ketones under the influence of TMSOTf providing a facile protocol for the synthesis of substituted indolizines, thus demonstrating the application of ketones as electrophiles in a two component Baylis-Hillman reaction.

Electrochemical site-selective direct C-H sulfenylation and selenylation of a chromone-fused-indolizine (CFI) skeleton.

Herein, for the first time, we report the transition metal-free electrochemical site-selective direct C-H sulfenylation/selenylation of chromone-fused indolizine compounds (CFIs) to afford the corresponding CFIs thioethers and selenoethers   in 58-96% yields. The developed protocol offers a transition metal-free, ligand-free, catalyst-free methodology and is suitable for a variety of chalcogenide molecules (S and Se) along with various electron-rich and electron-poor chromone-fused indolizine compounds. Cyclic voltammograms and control experiments also validated the plausible reaction pathway.

Blue LED-Mediated Syntheses of Arylazo Phosphine Oxides and Phosphonates via N-P Bond Formation.

The synthesis of (E)-diphenyl(aryldiazenyl)phosphine oxides and dialkyl (E)-(aryldiazenyl)phosphonates via visible light-mediated N-P bond formation between diazo species and phosphine oxides and phosphite derivatives, respectively, is described. The diazo species were generated via the reaction of aniline with isoamyl nitrite, which upon reaction with phosphorus surrogates generated arylazophosphine oxides and arylazo phosphonates in good to excellent yields. This sustainable chemical process offers a broad substrate scope and reasonably viable product formation.

Cesium carbonate-catalyzed synthesis of phosphorothioates via S-phosphination of thioketones.

A highly efficient and environmentally-friendly base-mediated transition metal-free direct thiophilic catalytic approach is reported for the synthesis of S-benzhydryl-phosphorothioates by reacting phosphite nucleophiles with diarylmethanethione. A wide variety of thioketones were coupled with different phosphite derivatives to provide the corresponding phosphorothioates in good to excellent yields. The control experiments and density functional theory (DFT) calculations rely on the regio-selective thiophilic addition of a phosphite nucleophile via umpolung protocols.

Electrochemical Synthesis of Carbodiimides via Metal/Oxidant-Free Oxidative Cross-Coupling of Amines and Isocyanides.

This work discloses an electrochemical oxidative cross-coupling of amines with aryl and aliphatic isocyanides. In an undivided cell, the reaction proceeds without involving any transition-metal catalyst, oxidant, or toxic reagents providing carbodiimides in good yields, thereby circumventing stoichiometric chemical oxidants, with H2 as the only byproduct. Moreover, carbodiimides were in situ converted into unsymmetrical ureas in moderate to good yields using an electricity ON-OFF strategy.

Engineered C-S Bond Construction.

Due to the versatile applications of thioethers and thioesters in organic synthesis, medicinal chemistry, the pharmaceutical industry, and materials science, recently the construction of C-S bonds has emerged as the forefront in the field of cross-coupling reactions. Enough progress has been made in this direction by using both metal catalysis and other alternative processes. A brief review of the recent developments in the area of C-S coupling reaction is described.

Transition-metal-catalyzed C-S bond coupling reaction.

Sulfur-containing molecules such as thioethers are commonly found in chemical biology, organic synthesis, and materials chemistry. While many reliable methods have been developed for preparing these compounds, harsh reaction conditions are usually required in the traditional methods. The transition metals have been applied in this field, and the palladium-catalyzed coupling of thiols with aryl halides and pseudo halides is one of the most important methods in the synthesis of thioethers. Other metals have also been used for the same purpose. Here, we summarize recent efforts in metal-catalyzed C-S bond cross-coupling reactions, focusing especially on the coupling of thiols with aryl- and vinyl halides based on different metals.

Metal-free sp(3) C-H functionalization: a novel approach for the syntheses of selenide ethers and thioesters from methyl arenes.

A DTBP-promoted metal-free and solvent-free formation of C-Se and C-S bonds through sp(3) C-H functionalization of methyl arenes with diselenides and disulfides is described.