Reaction of enamines with trifluoromethyl containing carbonyl reagents

The reaction of linear push-pull enamines bearing a methyl group at the α-position with a set of trifluoromethylated carbonyl compounds was investigated. It has been found that the reaction proceeds at the methyl group of the enamines. The first computational study of the reaction between push-pull enamines and strong electrophilic reagents was reported. Out of three pathways considered DFT and MP2 calculations support ene-mechanism previously suggested based on experimental results only.     

Trifluoromethylation of enamines under acidic conditions

A method for the trifluoromethylation of enamines using Me₃SiCF₃ leading to α-CF₃-substituted amines is described. The reaction is promoted by hydrofluoric acid generated from KHF₂ and either trifluoroacetic or triflic acid, and involves protonation of the enamine followed by transfer of the CF₃-carbanion from the silicon reagent to the cationic electrophile.     

Preparation of stable fulvene and difulvene aldehydes from benzaldehydes and an indene-derived enamine: formation of novel indene-fused benzodiazepines and attempted syntheses of di- and tricarbaporphyrinoid systems

Although carbaporphyrins and related systems have been widely studied, far less work has been carried out on the synthesis of porphyrin analogues with more than one carbocyclic subunit. Fulvene aldehydes are potentially valuable intermediates for studies of this type. A versatile methodology has been developed where benzaldehydes are reacted with an indene-derived enamine in the presence of dibutylboron triflate to give fulvene monoaldehydes. This chemistry allows halo, alkyl, methoxy or cyanovinyl units to be introduced and the resulting fulvenes are stable compounds that are easily purified by column chromatography. Isophthalaldehydes afford difulvene dialdehydes that are equally stable and these can be reduced with CeCl₃-NaBH₄ to give the related dicarbinols. The difulvene dialdehydes failed to give macrocyclic products when reacted with o-phenylenediamine in the presence of CeCl₃ but instead gave unprecedented bis-indene-fused benzodiazepines. Fulvene monoaldehydes also reacted under these conditions to give benzodiazepine products in good yields. These results highlight the potential utility of fulvene aldehydes for synthetic applications both inside and outside of the area of porphyrin analogue chemistry.     

Self-condensation of β-(isoxazol-5-yl) enamines under treatment with acetyl chloride and acids. Synthesis of novel 1,3-diisoxazolyl-1,3-dieneamines and 1,3,5-triisoxazolyl benzenes

Two directions for self-condensation of β-(isoxazol-5-yl) enamines under treatment with either acetyl chloride or acids were found leading to new 1,3-diisoxazolyl-1,3-dieneamines and 1,3,5-triisoxazolyl benzenes. The effect of solvent, acid, temperature and the reaction time on the ratio of reaction products were investigated. Trans-E-cis configuration of prepared 1,3-diisoxazolyl-1,3-dieneamines was unambiguously confirmed by 2D NMR spectra and X-ray analysis. A new mechanism of 1,3-diisoxazolyl-1,3-dieneamines formation was proposed.     

Synthesis of 6-nitro-4-sulfanyl-1H-indole derivatives from 2,4,6-trinitrotoluene

The synthesis of 6-nitro-4-sulfanyl-1H-indoles from 2,4,6-trinitrotoluene (TNT) is described. The first step is the nucleophilic substitution of an ortho-nitro group with a thiol to give the corresponding sulfide. The latter were transformed into the corresponding enamines upon treatment with dimethylformamide dimethyl acetal (DMF DMA). The enamines were converted into the indoles applying the Batcho–Leimgruber synthetic protocol.     

Detection of enantiomers of chiral primary amines by 1H NMR analysis via enamine formation with an enantiopure γ-position aldol product of a β-keto ester

A ¹H NMR analysis method that detects enantiomers of molecules bearing a primary amino group has been developed. The method uses a β-keto ester-derived probe that forms enamines with the amines and is able to discriminate enantiomers of functionalized amines and amines that have chiral centers at positions remote from the amine group.     

A one-pot domino reaction in constructing isoorotate bases and their nucleosides

A novel strategy, involving the coupling of enaminoesters with chlorosulfonyl isocyanate and accelerated by microwave irradiation, enables the straightforward preparation of the biologically important isoorotate bases. Extensions to nucleoside derivatives are also described.     

Studies on the Biginelli reaction: a mild and selective route to 3,4-dihydropyrimidin-2(1H)-ones via enamine intermediates

l-Proline methyl ester hydrochloride was found to be an effective catalyst for assembling (±)-dihydropyrimidinones under mild conditions. Mechanistic insights into the useful selectivity elements of this amine-catalyzed process are also reported.     

Hybrid hetarylhydrazones and enamines of Furan-2(3H)-ones as a framework for the synthesis of poly-N-heterocycles

Substituted furan-2(3H)-ones can act as platform compounds to obtain easily various functionalized derivatives as well as heterocycles with different heteroatoms patterns. In this study, we suppose a simple and effective way to reach poly-N-heterocycles using a set of hybrid hetarylhydrazones and enamines based on furan-2(3H)-ones as a starting material. The presence of a few reaction centers in these the hybrid furan-2(3H)-one derivatives allows them to undergo some intramolecular rearrengements with opening furan ring as well as with keeping it unaffected followed by the increase of complexity of the resulting heterocycles, depending on reaction conditions. It was found that the reaction conditions and the nature of the substituents in the hydrazone fragment affect the direction of the interaction and the nature of the resulting products. Different approaches form a framework which allowed us to create a library of substituted annelated poly-N-heterocycles with highly prominent biological effects. Analysis of the possible biological effects was performed in silico which allows us to reveal leading structures among all synthesized compounds.