Anatoly N. Vereshchagin

Electrocatalysis in MIRC reaction strategy: facile stereoselective approach to medicinally relevant spirocyclopropylbarbiturates from barbituric acids and activated olefins

The combined electrolysis of barbituric acids and benzylidenemalononitriles or benzylidenecyanoacetates in methanol in an undivided cell in the presence of sodium bromide results in efficient MIRC (Michael-initiated ring-closure) formation of the corresponding spirocyclopropylbarbiturates in 45–93% yield. The electrocatalytic reaction proceeds smoothly under neutral and mild conditions with benzylidenemalononitriles or benzylidenecyanoacetates bearing both electron-donating and electron-withdrawing groups. NMR and single X-ray diffraction studies indicate that the electrocatalytic MIRC transformation of barbituric acids and benzylidenecyanoacetates results in the stereoselective formation of spirocyclopropanes with an (E)-configuration of aryl and alkoxycarboxylate substituents. The implication of electrocatalysis in the MIRC reaction strategy allows the combination of the synthetic virtues of both methods and accounts for an efficient approach to medicinally relevant spirocyclopropylbarbiturates avoiding inconvenient direct use of molecular halogen or halogenated substrates in accordance with the concepts of modern green chemistry.

Electrochemical synthesis of cyclopropanes

Data on methods of electrochemical synthesis of cyclopropanes are summarized and described systematically. Direct electrochemical methods to afford cyclopropanes in both cathodic and anodic processes are considered. Among indirect electrochemical methods such as the processes employing electrogenerated bases and also those involving electrogenerated metal complexes, attention is focused on the most promising methods for the synthesis of functionally substituted cyclopropanes, namely, the electrocatalytic cascade and multicomponent transformations of CH acids and also the joint electrolysis of CH acids and activated alkenes or carbonyl compounds in the presence of alkali metal halides as mediators. The bibliography includes 62 references.

Electrocatalytic transformation of malononitrile and cycloalkylidenemalononitriles into spirotricyclic and spirotetracyclic compounds containing cyclopropane and pyrroline fragments

Electrolysis of cycloalkylidenemalononitriles and malononitrile in MeOH in an undivided cell in the presence of the NaBr—NaOMe mediator system gives spirotricyclic compounds containing cyclopropane and pyrroline fragments in 50—77% yields. Spirobicyclic and spirotricyclic tetracyanocyclopropanes undergo electrolysis in alcohols to afford spirotricyclic and spirotetracyclic products containing cyclopropane and pyrroline fragments in 50—93% yields.

Electrocatalytic transformation of malononitrile and cycloalkylidenemalononitriles into spirobicyclic and spirotricyclic compounds containing 1,1,2,2-tetracyanocyclopropane fragment

Electrolysis of malononitrile and cycloalkylidenemalononitriles in EtOH in an undivided cell in the presence of NaBr affords spirobicyclic compounds containing a 1,1,2,2-tetracyanocyclopropane fragment in 50—88% yields.

Electrocatalytic transformation of dialkyl malonates and arylidene- or alkylidenemalononitriles into dialkyl esters of 3-substituted 2,2-dicyanocyclopropane-1,1-dicarboxylic acids

Electrolysis of alcoholic solutions of dialkyl malonates and arylidene- or alkylidenemalononitriles in the presence of NaBr in an undivided cell gave dialkyl esters of 3-substituted 2,2-dicyanocyclopropane-1,1-dicarboxylic acids in 60–90% yields.

The first electrocatalytic stereoselective multicomponent synthesis of cyclopropanecarboxylic acid derivatives

The one-pot electrocatalytic domino transformation of aldehydes and two different C–H acids – alkyl cyanoacetate and dialkyl malonate in the presence of sodium bromide–sodium acetate as a double mediatory system in alcohol in an undivided cell (simple beaker) results in stereoselective formation of trialkyl(2R*,3R*)-3-aryl-2-cyanocyclopropane-1,1,2-tricarboxylates in 52–87% yields. This protocol uses group-assisted purification (GAP) chemistry in which the pure products were simply isolated by filtration from the reaction mixture. Developed electrocatalytic process allows to obtain multigramme-scale amount of trialkyl(2R*,3R*)-3-aryl-2-cyanocyclopropane-1,1,2-tricarboxylates.

Stereoselective electrocatalytic transformations of malononitrile and aromatic aldehydes into (1R,5S,6R)*-4,4-dialkoxy-2-amino-6-aryl-1,5-dicyano-3-azabicyclo[3.1.0]hex-2-enes

Electrolysis of aromatic aldehydes and malononitrile in alcohols in an undivided cell in the presence of a NaBr-NaOAc mediatory system stereoselectively gave bicyclic compounds containing the cyclopropane and pyrroline fragments in 60 to 70% yields. In the bicyclic products, the benzene and pyrroline rings are on different sides of the cyclopropane ring.

General approach to a spiro indole-3,1′-naphthalene tetracyclic system: stereoselective pseudo four-component reaction of isatins and cyclic ketones with two molecules of malononitrile

A new type of catalytic stereoselective cascade pseudo four-component reaction was discovered. The simple and facile pseudo four-component reaction of isatins, cyclic ketones with two molecules of malononitrile catalyzed by triethylamine at ambient temperature stereoselectively results in the formation of tetracyclic spirooxindoles in 60–90% yields. Thus, a new simple and efficient ‘one-pot’ method to synthesize substituted spirooxindoles was found directly from reasonable starting compounds. Unique stereoselectivety was achieved on two or three centers in this pseudo four-component reaction.

Stereoselective electrocatalytic cyclization of 3-substituted 2,2-dicyanocyclopropane-1,1-dicarboxylic acid esters to form 6-substituted (1R,5R,6R)*-4,4-dialkoxy-5-cyano-2-oxo-3-azabicyclo[3.1.0]hexane-1-carboxylic acid esters

Electrolysis of 3-substituted 2,2-dicyanocyclopropane-1,1-dicarboxylic acid esters in alcohols in an undivided cell in the presence of NaBr or NaOAc afforded 6-substituted (1R,5R, 6R)*-4,4-dialkoxy-5-cyano-2-oxo-3-azabicyclo[3.1.0]hexane-1-carboxylic acid esters in 80–95% yields.

Catalysis of Cascade and Multicomponent Reactions of Carbonyl Compounds and CH Acids by Electricity

This review is concerned with modern trends in the use of electrochemically induced chain reactions in cascade and multicomponent electroorganic synthesis. The review summarizes the data on the use of electrochemically induced chain reactions in cascade and multicomponent organic synthesis, which were published mainly in the last decade.