Pavel A. Belyakov

Reactions of Sulfur- and Phosphorus-Substituted Fluoroalkylating Silicon Reagents with Imines and Enamines under Acidic Conditions

Nucleophilic fluoroalkylation reactions of imines and enamines with α-phenylthio, α-phenylsulfonyl, and α-diethylphosphoryl substituted fluorinated silanes have been investigated. The reactions are promoted by hydrofluoric acid generated in situ from potassium hydrodifluoride and trifluoroacetic acid. Sulfur reagents worked well with both imines and enamines, whereas phosphorus reagent efficiently coupled only with enamines.

Trifluoromethylation of N-Benzoylhydrazones

A method for the nucleophilic trifluoromethylation of N-benzoylhydrazones using Me3SiCF3/AcONa has been described. The CN bond of the hydrazones is activated by difluoroboron group, which is introduced by means of boron trifluoride and allylsilane.

Fluorocyanation of enamines.

A method for the fluorocyanation of enamines has been described. The reaction involves fluorination of the electron rich double bond with N-F reagent (Selectfluor or NFSI) accompanied by trapping of beta-fluoroiminium cationic intermediate with cyanide nucleophile.

Electrochemically induced multicomponent assembling of isatins, 4-hydroxyquinolin-2(1H)-one and malononitrile: a convenient and efficient way to functionalized spirocyclic [indole-3,4′-pyrano[3,2-c]quinoline] scaffold

Electrochemically induced catalytic multicomponent transformation of isatins, 4-hydroxyquinolin-2(1H)-one and malononitrile in ethanol in an undivided cell in the presence of sodium bromide as an electrolyte results in the formation of spirooxindoles with fused functionalized indole-3,4′-pyrano[3,2-c]quinoline] scaffold in 75–91% substance yields and 500-600% current yield. The developed efficient electrocatalytic approach to medicinally relevant [indole-3,4′-pyrano[3,2-c]quinoline] scaffold is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a novel example of facile environmentally benign synthetic concept for electrocatalytic multicomponent reactions.

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.

Structure and Bonding Nature of the Strained Lewis Acid 3-Methyl-1-boraadamantane: A Case Study Employing a New Data-Analysis Procedure in Gas Electron Diffraction

Base-free 3-methyl-1-boraadamantane was synthesized by starting from its known THF adduct, transforming it to a butylate-complex with n-butyllithium, cleaving the cage with acetyl chloride to give 3-n-butyl-5-methyl-7-methylene-3-borabicyclo[3.3.1]nonane and closing the cage again by reacting the latter with dicyclohexylborane. The identity of 3-methyl-1-boraadamantane was proven by (1) H, (11) B and (13) C NMR spectroscopy and elemental analysis. The experimental equilibrium structure of the free 3-methyl-1-boraadamantane molecules has been determined at 100 °C by using gas-phase electron diffraction. For this structure determination, an improved method for data analysis has been introduced and tested: the structural refinement versus gas-phase electron diffraction data (in terms of Cartesian coordinates) with a set of quantum-chemically derived regularization constraints for the complete structure under optimization of a regularization constant, which maximizes the contribution of experimental data while retaining a stable refinement. The detailed analysis of parameter errors shows that the new approach allows obtaining more reliable results. The most important structural parameters are: r(e) (B-C)(av) =1.556(5) Å, angle(e) (C-B-C)(av) =116.5(2)°. The configuration of the boron atom is pyramidal with ∑ angle (C-B-C)=349.4(4)°. The nature of bonding was analyzed further by applying the natural bond orbital (NBO) and atoms in molecules (AIM) approaches. The experimentally observed shortening of the B-C bonds and elongation of the adjacent C-C bonds can be explained by the σ(C-C)→p(B) hyperconjugation model. Both NBO and AIM analyses predict that the B-C bonds are significantly bent in the direction out of the cage.

Synthesis of 2-monofunctionalized 2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-diones

New (1R*,5S*)-2-R-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-diones containing the terminal carboxy or hydroxy group in the substituent R were synthesized by cyclocondensation of 4,5-dihydroxyimidazolidin-2-one with 1-R-ureas. Single-crystal X-ray diffraction analysis showed that 2-carboxyethyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione crystallizes as a racemate.

Trifluoromethylation and pentafluorophenylation of enamines

A reaction of enamines with Me3SiCF3 and Me3SiC6F5 in the presence of carboxylic acids leading to α-CF3-and α-C6F5-substituted amines has been studied. 3-Cyanobenzoic acid was found to be the optimal promoter of these reactions.

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.

Reactions of (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester with vicinal mercaptonitriles. Synthesis of δ-hetaryl-substituted α-amino acids

The reactions of (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester with vicinal mercaptonitriles afforded δ-hetaryl-N-trifluoroacetyl-substituted α-amino acids (hetaryl is thiazol-2-yl, 2-thienyl, or thieno[2,3-b]pyridin-6-yl).