A new strategy of the chemical route to the cyclopropane structure: direct transformation of benzylidenemalononitriles and malononitrile into 1,1,2,2-tetracyanocyclopropanes

The new reaction was found: the direct formation of cyclopropanes from activated olefins and C-H acids. The action of free halogen or active halogen containing compounds on the equal amounts of benzylidenemalononitriles and malononitrile in basic alcohol solutions results in the formation of 3-aryl-1,1,2,2-tetracyanocyclopropanes in 65-95% yields. Thus, the new simple and efficient way to 3-aryl substituted tetracyanocyclopropanes was found directly from such simple and reasonable starting compounds as benzylidenemalononitriles and malononitrile.     

Synthesis of β-amino carbonyl compounds via a Zn(OTf)2-catalyzed cascade reaction of anilines with aromatic aldehydes and carbonyl compounds

A Zn(OTf)₂-catalyzed cascade reaction of anilines with aromatic aldehydes and carbonyl compounds was described. This one-pot three-component reaction afforded the corresponding β-amino carbonyl compounds, β-amino esters, and β-amino ketones in good to excellent yields. The reaction was also applied for the liquid-phase synthesis of β-amino carbonyl compound library using PEG as a support.     

Solvent-free cascade reaction: direct multicomponent assembling of 2-amino-4H-chromene scaffold from salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes

The new type of solvent-free cascade reaction was found: the direct heating of the mixture of salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes at 60 °C in the presence of catalytic amounts of KF or NaOAc results in the formation of 2-amino-4-(1-nitroalkyl)-4H-chromene-3-carbonitriles or methyl 2-amino-4-(1-nitroalkyl)-4H-chromene-3-carboxylates in 80-90% yields. Thus, the new simple and efficient solvent-free ‘one-pot’ way to substituted medicinally privileged 2-amino-4H-chromene scaffold was found directly from such simple and reasonable starting compounds as salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes.     

Electrochemically induced Henry reaction of nitromethane and carbonyl compounds

The electrolysis of carbonyl compounds and nitromethane in methanol or in the mixture of methanol and DMF in an undivided cell results in the formation of corresponding β-nitroalcohols in 60-75% yields. Thus, the simple electrocatalytic system can produce under mild conditions an electrochemically induced Henry reaction.     

Aryne insertion into α-cyanocarbonyl compounds: direct introduction of carbonyl and cyanomethyl moieties into the aromatic skeletons

Two different carbon functional groups can be introduced simultaneously into 1,2-positions of aromatic skeletons based upon a novel insertion reaction of arynes into a carbonyl-cyanomethyl σ-bond of α-cyanocarbonyl compounds.     

Novel and efficient Ni-mediated pinacol coupling of carbonyl compounds

It was firstly found that the Rieke Ni generated in situ was able to promote the pinacol coupling of various carbonyls efficiently. Based on this information, another catalytically effective, cheaper and more convenient NiCl₂(Cat.)/Mg/TMSCl system was designed and developed further successfully. The interesting single-electron transfer (SET) mechanisms for the coupling reactions were proposed. Additionally, the dl/meso diastereoselectivity and some additive effects were also explained in terms of the proposed mechanisms.     

Trifluoromethylation of carbonyl compounds with sodium trifluoroacetate

In the presence of copper(I) iodide as catalyst, a variety of carbonyl compounds, such as aldehydes, ketones and acid anhydrous, could be trifluoromethylated with sodium trifluoroacetate to give the corresponding alcohols in moderate to high yields, and a possible mechanism was proposed to explain the roles of catalyst and solvent in the reaction system.     

Unexpected cascade transformations in the reaction of aromatic aldehydes with the malononitrile dimer

The one-pot reaction of aromatic aldehydes, malononitrile dimer, and triethylamine unexpectedly led to ammonium salts of not previously assumed 5,7-diamino-4-aryl-2-(dicyanomethyl)-1,4-dihydro-1,8-naphthyridine-3,6-dicarbonitriles, but the isomeric 5,7-diamino-4-aryl-2-(dicyanomethyl)-1,4-dihydro-1,6-naphthyridine-3,8-dicarbonitriles. Following neutralization and dehydrogenation led to the new, annulated with pyridine ring tricyanopyridines (TCPy).     

N-heterocyclic carbene catalyzed cyanation reaction of carbonyl compounds with ethyl cyanoformate and acetyl cyanide

N-heterocyclic carbene (NHC) has been employed as an efficient catalyst for cyanation reaction of carbonyl compounds. Under catalysis of 1 mol % NHCs, various aldehydes and 2,2,2-trifluoroacetophenone coupled with ethyl cyanoformate in THF to provide cyanohydrins ethyl carbonates in excellent yields. While in the presence of 10 mol % catalyst, different types of aldehydes and 2,2,2-trifluoroacetophenone reacted with acetyl cyanide in dichloroethane to give acylated cyanohydrins in moderate to high yields.     

Synthetic methods,III: Sulfated zirconia catalyzed thioacetalization of carbonyl compounds

Summary Sulfated zirconia effectively catalyzes the reaction of carbonyl compounds with 1,2-ethanedithiol or thiophenol to afford the corresponding dithioacetals as useful organosulfur synthons. Isolation of pure products in high yields by simple filtration and evaporation is an important feature of this method.

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Synthetische Methoden, 3. Mitt.: Thioacetalisierung von Carbonylverbindungen mit ZrO₂SO ₄ ^2– (Kurze Mitt.)

Zusammenfassung ZrO₂/SO _2– ⁴ katalysiert die Reaktion von Carbonylverbindungen mit 1,2-Ethandiol oder Thiophenol zu den als Organoschwefelsynthonen wertvollen entrsprechenden Dithioacetalen. Ein wichtiges Merkmal der Methode ist die einfache Isolierung der Produkte in guten Ausbeuten durch Filtration und Entfernung des Lösungsmittels.

     

Electrocatalytic multicomponent cyclization of an aldehyde, malononitrile and a malonate into 3-substituted-2,2-dicyanocyclopropane-1,1-dicarboxylate—the first one-pot synthesis of a cyclopropane ring from three different molecules

Electrolysis of an aldehyde, malononitrile and a malonate in an alcohol in an undivided cell in the presence of sodium acetate-sodium halide as a double mediatory system results in the formation of 3-substituted-2,2-dicyanocyclopropane-1,1-dicarboxylates in 40-60% yields.     

Reaction of halothane with carbonyl compounds in the presence of bases

The reaction of halothane, 2-bromo-2-chloro-1,1,1-trifluoroethane (1), with aldehydes and ketones in the presence of bases was found to give 1-alkyl- or 1-aryl-2-bromo-2-chloro-3,3,3-trifluoropropanols (2) or 2-chloro-3,3-difluoro-2-propenols (3) selectively in good to moderate yields depending on the bases and reaction conditions.     

First example of continuous-flow reaction conditions for biomimetic reductive amination of fluorine-containing carbonyl compounds

This study presents the first example of continuous-flow reaction conditions for biomimetic reductive amination of fluorinated carbonyl compounds using silica-adsorbed DBU as catalyst for on-column process. This new on-column process features operationally convenient conditions, higher chemical yields and purity of products as compared with traditional in-flask reactions. Furthermore the removal of base-catalyst is not an issue in this process at all, as the catalyst (DBU) remains on the column in the “reaction zone”, the feature which makes the overall process substantially more efficient and inexpensive, in particular, for large-scale synthesis of the target α-perfluoroalkyl amines.     

Pentamethylcyclopentadienide in organic synthesis: nucleophilic addition of lithium pentamethylcyclopentadienide to carbonyl compounds and carbon-carbon bond cleavage of the adducts yielding the parent carbonyl compounds

Lithium pentamethylcyclopentadienide (C₅Me₅Li, Cp*Li) reacted with aromatic aldehyde to provide the corresponding carbinol in excellent yield. The carbinol returns to the parent aldehyde and pentamethylcyclopentadiene upon exposure to acid or due to heating. Chlorodimethylaluminum is essential as an additive to attain the nucleophilic addition of Cp*Li to aliphatic aldehyde. The carbinol derived from aliphatic aldehyde returns to the parent aldehyde and pentamethylcyclopentadiene by the action of a catalytic amount of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). The reversible addition/elimination of the Cp* group can represent a protection of aldehyde. Mechanistic details of the carbon-carbon bond cleavage are also disclosed.     

Enatioselective organocatalytic synthesis of highly functionalized tetrahydrothiophenes by a Michael-aldol cascade reaction

A catalytic asymmetric Michael-aldol cascade process for efficient synthesis of trisubstituted tetrahydrothiophenes is reported with high enantio- and diastereo-selectivities. Notably, three consecutive stereogenic centers including one chiral quaternary carbon center are efficiently created in the ‘one-pot’ operation.