Electrochemical quinuclidine-mediated Minisci-type acylation of N-heterocycles with aldehydes.

The electro-generation of acyl radicals from both aromatic and aliphatic aldehydes remains an unmet challenge. We provide a solution to this challenge by merging electro-oxidation and a quinuclidine-mediated hydrogen atom transfer strategy. The generation of acyl radicals at decreased applied potentials compared to that of formyl oxidation exhibits excellent functional group compatibility.

Paired Electrolysis Enabled Trifluoromethylheteroaromatization of Alkenes and Alkyne with Trifluoromethyl Thianthrenium Triflate (TT-CF3+OTf-) as a Bifunctional Reagent.

We report a strategic exploitation of trifluoromethyl thianthrenium triflate (TT-CF3+OTf-) as both electromediator and CF3 radical precursors for paired electrolysis. Enabled by this strategy, the three-component trifluoromethylheteroaromatization of alkenes and alkynes was realized. The superiority of TT-CF3+OTf- to other electrophilic CF3 reagents is attributed to the cathodic generation of thianthrene (TT) as a mediator, which shifts the heterogeneous oxidation of interest to a homogeneous one.

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH4I.

The electrochemical preparation of 2-aminothiazoles has been achieved by the reaction of active methylene ketones with thioureas assisted by ᴅʟ-alanine using NH4I as a redox mediator. The electrochemical protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including ß-keto ester, ß-keto amide, ß-keto nitrile, ß-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically, the in situ generated α-iodoketone was proposed to be the key active species.

One-Pot Anodic Conversion of Symmetrical Bisamides of Ethylene Diamine to Unsymmetrical gem-Bisamides of Methylene Diamine.

Symmetrical bisamides of ethylene diamine of type ArCONHCH2CH2NHCOAr undergo anodic C-C bond cleavage in acetonitrile-LiClO4 under controlled-potential electrolysis. The electrogenerated carbocation intermediates react with the solvent acetonitrile to afford unsymmetrical gem-bisamides of type ArCONHCH2NHCOMe in a one-pot reaction. The yields of the latter products are moderate (up to 60%). Other minor products involve two symmetrical gem-bisamides of type ArCONHCH2NHCOAr and MeCONHCH2NHCOMe and fragmentation products (e.g., ArCONHCHO, ArCONH2, and ArCN).

Functionalization of N-arylglycine esters: electrocatalytic access to C-C bonds mediated by n-Bu4NI.

An efficient electrocatalytic functionalization of N-arylglycine esters is reported. The protocol proceeds in an undivided cell under constant current conditions employing the simple, cheap and readily available n-Bu4NI as the mediator. In addition, it is demonstrated that the mediated process is superior to the direct electrochemical functionalization.

Electrocatalytic Minisci Acylation Reaction of N-Heteroarenes Mediated by NH4I.

An electrochemical C-H acylation of electron-deficient N-heteroarenes with α-keto acids is reported. This first electrochemical Minisci acylation reaction proceeded using NH4I as a redox catalyst. A broad N-heteroarene scope and high functional group tolerance are observed. Selective monoacylation of N-heteroarenes is achieved via control of acyl radical at a low concentration. The results of cyclic voltammetry and control experiments disclose that the electrogenerated I2 is likely the active species to initiate the oxidative decarboxylation of carboxylate anion via an acyl hypoiodite intermediate. The electrochemical Minisci acylation provides a straightforward approach for the late-stage functionalization of pharmacophores.

Electrochemically Oxidative α-C-H Functionalization of Ketones: A Cascade Synthesis of α-Amino Ketones Mediated by NH4I.

An efficient electrochemical protocol for the synthesis of α-amino ketones via the oxidative cross-dehydrogenative coupling of ketones and secondary amines has been developed. The electrochemistry performs in a simple undivided cell using NH4I as a redox catalyst and a cheap graphite plate as electrodes under constant current conditions. Gram-scale reaction demonstrates the practicality of the protocol. The reaction is proposed to procced through an initial α-iodination of ketone, followed by a nucleophilic substitution of amines.

Electrochemical Oxidative Amination of Sodium Sulfinates: Synthesis of Sulfonamides Mediated by NH4I as a Redox Catalyst.

An efficient protocol for the synthesis of sulfonamides via the electrochemical oxidative amination of sodium sulfinates has been developed. The chemistry proceeds in a simple undivided cell employing a substoichiometric amount of NH4I that serves both as a redox catalyst and a supporting electrolyte; in this manner additional conducting salt is not required. A wide range of substrates, including aliphatic or aromatic secondary and primary amines, as well as aqueous ammonia, proved to be compatible with the protocol. Scale-up was possible, thereby demonstrating the practicality of the approach. The electrolytic process avoids the utilization of external oxidants or corrosive molecular iodine and therefore represents an environmentally benign means by which to achieve the transformation.

Aromatic C-H Bond Functionalization Induced by Electrochemically in Situ Generated Tris(p-bromophenyl)aminium Radical Cation: Cationic Chain Reactions of Electron-Rich Aromatics with Enamides.

An effective Friedel-Crafts alkylation reaction of electron-rich aromatics with N-vinylamides, induced by electrochemically in situ-generated TBPA radical cation, has been developed; the resulting adducts are produced in good to excellent yields. In the "ex-cell" type electrolysis, TBPA is transformed to its oxidized form in situ and subsequently employed as an electron transfer reagent to initiate a cationic chain reaction. An easily recoverable and reusable polymeric ionic liquid-carbon black (PIL-CB) composite was also utilized as a supporting electrolyte for the electrochemical generation of TBPA cation radical, without sacrificing efficiency or stability after four electrolyses. Cyclic voltammetry analysis and the results of control experiments demonstrate that the reaction of electron-rich aromatics and N-vinylamides occurs via a cationic chain reaction, which takes place though an oxidative activation of a C-H bond of electron-rich aromatics instead of oxidation of the N-vinylamide as previously assumed.

Electrocatalytic aziridination of alkenes mediated by n-Bu4NI: a radical pathway.

Efficient electrocatalytic aziridination of alkenes has been achieved for the first time. A structurally broad range of aziridines was easily accessed using an undivided cell operated at constant current and mediated by a catalytic quantity of n-Bu4NI. The electrocatalytic reaction also proceeded in the absence of additional conducting salt. The aziridination is proposed to follow a radical mechanism.

Polymeric ionic liquid and carbon black composite as a reusable supporting electrolyte: modification of the electrode surface.

One of the major impediments to using electroorganic synthesis is the need for large amounts of a supporting electrolyte to ensure the passage of charge. Frequently this causes separation and waste problems. To address these issues, a polymeric ionic liquid-Super P carbon black composite has been formulated. The system enables electrolyses to be performed without adding an additional supporting electrolyte, and its efficient recovery and reuse. In addition, the ability of the composite to modify the electrode surface in situ leads to improved kinetics. A practical consequence is that one can decrease catalyst loading without sacrificing efficiency.

Electrochemically induced ring-opening/Friedel­Crafts arylation of chalcone epoxides catalyzed by a triarylimidazole redox mediator.

The indirect anodic oxidation of chalcone epoxides in the presence of electron-rich heteroarenes mediated by a triarylimidazole (Med) was investigated by cyclic voltammetry (CV) and controlled potential electrolysis. The CV results indicate that a homogeneous electron transfer between Med•+ and chalcone epoxides is facilitated by an electron-rich heteroarene that serves as an arylation reagent. The preparative scale electrolysis generated epoxide-ring-opened/Friedel­Crafts arylation products in moderate to good yields. The fact that only a catalytic amount of charge was required suggests that Med•+ initiates a chain reaction. In addition, overoxidation of the products is avoided even though their oxidation potential is less than that of the starting chalcone epoxides.

Electrochemically initiated oxidative amination of benzoxazoles using tetraalkylammonium halides as redox catalysts.

An electrochemically promoted coupling of benzoxazoles and amines has been developed, leading directly to the formation of 2-aminobenzoxazoles. The chemistry utilizes catalytic quantities of a tetraalkylammonium halide redox catalyst and is carried out under constant current conditions in a simple undivided cell. The use of excess chemical oxidant or large amounts of supporting electrolyte is avoided. This greatly simplifies the workup and isolation process and leads to a reduction in waste.

Triarylimidazole redox catalysts: electrochemical analysis and empirical correlations.

A series of triarylimidazoles was synthesized and characterized electrochemically. The synthetic route is general, providing a pathway to 30 redox mediators that exhibit a > 700 mV range of accessible potentials. Most of the triarylimidazoles display three oxidation peaks where the first redox couple is quasi-reversible. The electronic character of the substituents affects the oxidation potential. This is exemplified by a linear correlation between the first oxidation potential and the sum of the Hammett σ(+) substituent constants, as well as with a series of calculated ionization potentials. We close by putting forward a rule of thumb stating that for a given mediator, the upper limit of accessible potentials can be extended by at least 500 mV beyond the largest recorded value. A rationale, the conditions under which the rule is likely to apply, and an example are provided.

Novel triarylimidazole redox catalysts: synthesis, electrochemical properties, and applicability to electrooxidative C-H activation.

A new class of metal-free, easy to synthesize redox catalysts based on a triarylimidazole framework is described. With those synthesized thus far, one can access a potential range of ca. 410 mV. They proved to be useful mediators for the activation of benzylic C-H bonds under mild conditions.

Anodic oxidation of catechols in the presence of alpha-oxoketene N,N-acetals with a tetrahydropyrimidine ring: selective alpha-arylation reaction.

The electrochemical oxidation of catechols leads to the formation of o-benzoquinones. This property has been applied to effectively synthesize alpha-arylated products of alpha-oxoketene N,N-acetals with a tetrahydropyrimidine ring.

Design, synthesis and anti-HIV integrase evaluation of N-(5-chloro-8-hydroxy-2-styrylquinolin-7-yl)benzenesulfonamide derivatives.

Styrylquinoline derivatives are demonstrated to be HIV-1 integrase inhibitors. On the basis of our previous CoMFA analysis of a series of styrylquinoline derivatives, N-[(2-substituted-styryl)-5-chloro-8-hydroxyquinolin-7-yl]-benzenesulfonamide derivatives were designed and synthesized,and their possible HIV IN inhibitory activity was evaluated.

One-pot electrochemical synthesis of fused indole derivatives containing active hydroxyl groups in aqueous medium.

An novel and convenient electrochemical approach was developed for the synthesis of indole derivatives from catechols and alpha-oxoheterocyclic ketene N,O-acetals. This method provides an environmentally benign access to fused indole derivatives containing active hydroxyls and carbonyl under mild reaction conditions.

Design, synthesis and anti-HIV integrase evaluation of 4-oxo-4H-quinolizine-3-carboxylic acid derivatives.

4-Oxo-4H-quinolizine-3-carboxylic acid derivatives bearing sulfamido, carboxylamido, benzimidazole and benzothiazole substituents have been designed and synthesized. The structures of these new compounds were confirmed by (1)H-NMR, (13)C- NMR, IR and ESI (or HRMS) spectra. Compounds were screened for possible HIV integrase inhibitory activity.

Anodic oxidation of mono- and disubstituted 1,4-dimethoxybenzenes.

The electrochemical oxidation of mono- and disubstituted 1,4-dimethoxybenzene derivatives with zero, one, and two benzylic CH(2)X groups (X = OAc, Cl, OH) (5a-c and 6a-c) has been carried out by using both constant-current and controlled-potential techniques in methanol and in the presence of different electrolytes and working electrodes. Constant-current electrolysis in KOH-methanol solutions yielded mostly the corresponding 1,4-quinone derivatives from 5a-c and 6b, whereas the disubstituted 1,4-dimethoxybenzenes 6a,c underwent side-chain oxidation to form 2,5-dimethoxyterephthalaldehydes. Upon alteration of the medium from the commonly used basic KOH-methanol to neutral LiClO(4)-methanol, a new spectrum of products was achieved in most cases, involving novel coupling products from monosubstituted substrates and quinone derivatives from disubstituted ones. Controlled-potential oxidation at the glassy carbon anodes and in a neutral LiClO(4)-methanol medium led to more complex mixtures of products, namely, polymers and new coupling products from monosubstituted substrates and quinones and side-chain oxidation (or substitution) products from the disubstituted ones. Three new coupling products were isolated and characterized by X-ray measurements.