External Oxidant-free Conditions Research Articles

Direct Cyanation of Thiophenols or Thiols to Access Thiocyanates under Electrochemical Conditions.

A novel electrochemical cross-coupling method for the synthesis of thiocyanates via the direct cyanation of readily available thiophenols or thiols with trimethylsilyl cyanide (TMSCN) was developed. This approach was also suitable for selenols. External oxidant-free, transition-metal-free and mild operating conditions were the main advantages of this protocol. A series of thiocyanates and selenocyanates could be obtained in moderate to high yields.

Electrochemical Organoselenium-Catalyzed Intermolecular Hydroazolylation of Alkenes with Low Catalyst Loadings.

The organoselenium-catalyzed amination of alkenes is a promising way to construct functionalized amines. However, the use of chemical oxidants and the unavoidable formation of allylic amine or enamine are the two main limitations of these methodologies. Against this background, we herein report an electro-selenocatalytic regime for the hydroazolylation of alkenes with azoles under external oxidant-free conditions with low catalyst loadings. Moreover, this protocol enables the generation of amines without vinyl substituents.

Electrochemical Benzylic C(sp3)-H Isothiocyanation.

Selective C(sp3)-H isothiocyanation represents a significant strategy for the synthesis of isothiocyanate derivatives. We report herein an electrochemical benzylic isothiocyanation in a highly chemo- and site-selective manner under external oxidant-free conditions. The high chemoselectivity is attributed to the facile in situ isomerization of benzylic thiocyanates to isothiocyanates. Notably, the method exhibits high functional group compatibility and is suitable for late-stage functionalization of bioactive molecules.

Electrophotocatalytic C-H Functionalization of N-Heteroarenes with Unactivated Alkanes under External Oxidant-Free Conditions.

The Minisci alkylation of N-heteroarenes with unactivated alkanes under external oxidant-free conditions provides an economically attractive route to access alkylated N-heteroarenes but remains underdeveloped. Herein, a new electrophotocatalytic strategy to access alkyl radicals from strong C(sp3 )-H bonds was reported for the following Minisci alkylation reactions in the absence of chemical oxidants. This strategy realized the first example of cerium-catalyzed Minisci alkylation reaction directly from abundant unactivated alkanes with excellent atom economy. It is anticipated that the general design principle would enrich catalytic strategies to explore the functionalizations of strong C(sp3 )-H bonds under external oxidant-free conditions with H2 evolution.

Electrochemical selenium-π-acid promoted hydration of alkynyl phosphonates.

An unprecedented electrochemical selenium-π-acid promoted hydration of internal alkynes bearing a phosphonate auxiliary was described. Thus, valuable (hetero)aryl and alkyl ketones could be accessed under mild, metal- and external oxidant-free conditions. This protocol features high atom-economy, good chemo- and regio-selectivity, excellent functional group tolerance and easily transformable products. Control experiments demonstrate that phosphonate assistance is essential for this transformation.

Electrochemical-induced benzyl C–H amination towards the synthesis of isoindolinones via aroyloxy radical-mediated C–H activation

A novel electrochemical strategy for the synthesis of valuable isoindolinones has been developed with the use of simple o-alkylbenzoic acid and alkyl nitrile as starting materials under metal-catalyst and external oxidant-free conditions.

Ru(II)-Catalyzed Regioselective C-N Bond Formation on Benzothiazoles Employing Acyl Azide as an Amidating Agent.

A Ru(II)-catalyzed regioselective direct ortho-amidation of 2-aryl benzo[d]thiazoles employing acyl azides as a nitrogen source has been accomplished. This approach utilizes the efficiency of benzothiazole as a directing group and the role of acyl azide as an effective amidating agent toward C–N bond formation, thereby evading the general Curtius rearrangement. The protocol highlights significant functional group tolerance, single-step, and external oxidant-free conditions, with the release of only innocuous molecular nitrogen as the byproduct. The reaction mechanism and the intermediates associated with this selective Ru-catalyzed reaction have been investigated using ESI-MS. The protocol also aided in the construction of ortho-amidated β-carbolines, unveiling another class of fluorescent molecules.

Electrochemical Generation of a Nonstabilized Azomethine Ylide: Access to Substituted N-Heterocycles.

Azomethine ylides are fascinating 1,3-dipoles for [3 + 2] cycloaddition reactions toward the construction of N-heterocycles. Herein, an efficient and environmentally benign electrochemical approach for the generation of a nonstabilized azomethine ylide has been established under metal-free and external oxidant-free conditions. The resulting 1,3-dipole undergoes a [3 + 2] cycloaddition reaction with olefins. This electrosynthetic methodology indulges a straightforward and facile approach for the construction of substituted pyrrolidines.

Catalyst-free, direct electrochemical trifluoromethylation/cyclization of N-arylacrylamides using TfNHNHBoc as a CF3 source

A new electrochemical strategy for trifluoromethylation/cyclization using TfNHNHBoc as a CF3 source was established. This approach was realized by the direct electrolysis of TfNHNHBoc under external oxidant-free and catalyst-free conditions, and afforded various trifluoromethylated oxindoles with good functional group compatibility and broad substrate scope. Preliminary mechanistic studies show that the reaction proceeds by a radical process.

Electrochemical Tri‐ and Difluoromethylation‐Triggered Cyclization Accompanied by the Oxidative Cleavage of Indole Derivatives

Considering their unique roles in organic synthesis, and pharmaceutical and agrochemical applications, the development of fluoroalkylation, cyclization, and indole oxidative cleavage are important topics. Herein, an unprecedented electrochemical tri- and difluoromethylation/cyclization/indole oxidative cleavage process occurring in an undivided cell is presented. The protocol employs a readily prepared Langlois reagent as the fluoroalkyl source, affording a series of tri- or difluoromethylated 2-(2-acetylphenyl)isoquinoline-1,3-diones in good yields with excellent stereoselectivity. It is worth noting that this new methodology merges the fluoroalkylation/cyclization of N-substituted acrylamide alkenes with the oxidative cleavage of an indole C(2)=C(3) bond under external oxidant-free conditions.

C-H Amidation and Amination of Arenes and Heteroarenes with Amide and Amine using Cu-MnO as a Reusable Catalyst under Mild Conditions.

An atom-economical and efficient route for the direct amidation and amination of aryl C-H bonds using our synthesized recyclable heterogeneous Cu-MnO catalyst is reported here. The direct C-H amidation was carried out using a simple amide without any preactivated coupling partner, and simple air was used as the sole oxidant. The reaction proceeds very smoothly with a broad range of substrates containing numerous functional groups in very good to excellent yields. Direct C-H aminations with a secondary amine were carried out under base-, ligand-, and external oxidant-free conditions in very good to excellent yields in very mild conditions. Both the amidation and amination can be scaled up on a gram scale with similar yields. The major advantage is that our catalyst is recyclable and reused several times without any significant loss of reactivity.

N-Tosylhydrazone as an oxidizing directing group for the redox-neutral access to isoquinolines via Cp∗Co(III)-Catalyzed C–H/N–N activation

Herein, an efficient and economic access has been revealed for the synthesis of isoquinolines via C–H bond activation strategy by using comparatively inexpensive and versatile cobalt catalyst. A hardly investigated directing group, N-tosylhydrazone has been effectively applied as an internal oxidant for an annulation reaction with internal alkynes via C–H/N–N bond functionalization. This catalytic protocol works for the extensive variety of substrates in moderate to excellent yields under external oxidant-free conditions. Additionally, the proposed protocol has advantages such as broad substrate coverage with significant product yields, readily synthesized substrates as well as scalability up to the gram quantity which further improves the competency of the methodology.

Iron-Catalyzed Triazole-Enabled C–H Activation with Bicyclopropylidenes

C–H/C–C functionalizations with oxymethylated bicyclopropylidenes were accomplished with an iron catalyst under external oxidant-free conditions. The combination of the unique reactivity of bicyclo...

Cobalt(III)-catalyzed C-H amidation of N,N-dialkyl thiobenzamides by sulfur coordination.

An efficient inexpensive cobalt(III)-catalyzed intermolecular amidation of N,N-dialkyl thiobenzamides with 1,4,2-dioxazol-5-ones via C-H bond activation is described. The reaction proceeds with high functional group tolerance under external oxidant free conditions, providing a straightforward approach for the direct modification of thioamide derivatives, which are prevalent organic motifs found in vital biological and pharmaceutical molecules.

Electrochemical oxygenation of sulfides with molecular oxygen or water: switchable preparation of sulfoxides and sulfones.

A practical and eco-friendly method for the controllable aerobic oxygenation of sulfides by electrochemical catalysis was developed. The switchable preparation of sulfoxides and sulfones was effectively controlled by reaction time, in which both molecular oxygen and water can be used as the oxygen source under catalyst and external oxidant-free conditions. The electrochemical protocol features a broad substrate scope and excellent site selectivity and is successfully applied to the modification of some sulfide-containing pharmaceuticals and their derivatives.

Photoredox/Cobalt-Catalyzed C(sp3)-H Bond Functionalization toward Phenanthrene Skeletons with Hydrogen Evolution.

The first example of photoredox strategy for synthesis of phenanthrene skeletons through C(sp3)-H functionalization under external oxidant-free conditions is achieved. This transformation relies on the keto-enol tautomerism of 1,3 dicarbonyl moiety, i.e., the enol form of 1,3-dicarbonyl derivatives with relatively lower oxidation potential can be activated by the excited acridinium photocatalyst. The electron and proton eliminated from the substrate are immediately captured by a cobaloxime catalyst to exclusively afford a-carbonyl radical for highly substituted 10-phenanthrenols in good to excellent yields.

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.

Electrochemical Ring Expansion to Synthesize Medium-Sized Lactams Through C–C Bond Cleavage

Medium-sized nitrogen heterocycles are prevalent motifs in many kinds of bioactive molecules and natural products. Owing to the unfavorable enthalpic and entropic barriers during the transition sta...

Electrochemical Oxidative Dehydrogenative Phosphorylation of N-Heterocycles with P(O)-H Compounds in Imidazolium-Based Ionic Liquid.

We report a direct and green electrochemical oxidative cross-dehydrogenative coupling reaction of N-heterocycles with hydrogen phosphoryl compounds under external oxidant-free conditions. Various phosphorylation products of substituted carbazoles and indoles are assembled in modest to excellent yields. A hydrogen release process is preliminarily demonstrated and H2 is the sole byproduct. An imidazolium based ionic liquid is selected as the optimal electrolyte.

Direct electrooxidation of alkynes to benzoin bis-ethers

Electrosynthesis of benzoin bis-ethers from alkynes and alcohols under metal-free and external oxidant free conditions.