A. Yu. Rulev

Unsaturated polyfluoroalkyl ketones in the synthesis of nitrogen-bearing heterocycles

This review focuses on the recent achievements and new developments in the synthesis of polyfluorinated aza-heterocycles based on fluorine-bearing enones and ynones published in the last decade.

Recent advances in Michael addition of H-phosphonates

The review discusses recent achievements in the development of more environmentally friendly and economically competitive processes for the synthesis of biologically and synthetically important phosphorus-bearing compounds by conjugate addition of hydrogen-phosphonates to different Michael acceptors.

Assembly of nitrogen-containing heterocycles initiated by the aza-Michael reaction

The aza-Michael reaction is considered as the most popular method for the carbon–nitrogen bond formation and the shortest way to β-aminocarbonyl compounds, including β-amino acids and their derivatives. In many cases, conjugate addition of nitrogen-centered nucleophiles to the activated multiple bond triggers a series of cascade transformations being completed by the formation of heterocycles and analogs of natural compounds. The review summarizes the most important advances in the aza-Michael reaction-initiated synthesis of nitrogen-containing heterocycles from unsaturated ketones and enoates.

Capto-Dative Acylenamines in the Reactions with Dialkyl Hydrogen Phosphites: One-Pot Transformation of α-Formylated Enamines to the Esters of N,N-Disubstituted α-Aminoacids

Abstractα-Acylenamines with terminal double bond CH2 = CH(NR2)COMe add dialkyl hydrogen phosphites to form only the Michaelis adducts. Contrary to that hydrophosphorylation of α-formylated enamines proceeds regiospecifically at C=O bond. Subsequent isomerization of the products of 1,2-addition and the cleavage of P-C bond of the intermediate α-keto-β-aminophosphonate yields N,N-disubstituted α-aminocarboxylates.

Stereoelectronic structure of α-bromoalkenyl trifluoromethyl ketones

The results of quantum-chemical calculations at the B3LYP/6-311G** level of theory showed that (Z)-α-bromo-β-arylalkenyl trifluoromethyl ketones are more stable than the corresponding E isomers by 4–5 kcal/mol. Relatively large positive charge on the olefinic β-carbon atom and strong polarization of the C=C bond in both Z-s-cis and Z-s-trans conformers makes bromoalkenyl trifluoromethyl ketones the most potent Michael acceptors among α,β-unsaturated carbonyl compounds. The calculated data are very consistent with the experimental IR spectra.

MULTISTEP NUCLEOPHILIC SUBSTITUTION OF THE HALOGEN ATOM IN 2-HALO-2-ALKENALS

Abstractpso-Substitution of the halogen atom in 2-halo-2-alkenals under the action of secondary amines proceedsvia three consecutive steps: addition, nucleophilic substitution, and β-elimination (the AdN-SN-E mechanism). The main intermediates arising in the reactions of 2-chloropropenal and 2-chloro-2-butenal with piperidine were detected by NMR spectroscopy. A general scheme of the reaction is proposed.

Protonation regioselectivity and rates of hydrolysis of α-piperidino-and α-morpholinocrotonaldehydes, and E,Z-isomerization of their enammonium salts

Conclusions1.α-Piperidino- and α-morpholinocrotonaldehydes react with HCl, CF3COOH, and CCl3COOH to give enammonium ion salts exclusively.2.Based on NMR data, at −20°C E forms of the enammonium salts are formed first and gradually isomerized to the corresponding Z forms.3.The relative rates of hydrolysis of α-piperidino- and α-morpholinocrotonaldehydes, leading to the formation of ethylglyoxal and free amine, were also determined.

Unusual reaction of bromoalkyl trifluoromethyl ketones with symmetrically disubstituted ethylenediamines. Theoretic investigation applying methods of density functional and multiparticle perturbation theory МР-2

Mechanism of a multistage reaction between α-bromotrifluoromethylenones and N,N′-dialkylethylenediamines was examined in detail using quantum chemical methods of density functional (non-empirical functional РВЕ, extended split TZp-basis) and multiparticle perturbation theory МР-2, basis 6-311+G(d,p), in the gas phase approximation, and also including solvents molecules (water and 2,2,2-trifluoroethanol). The specific solvation of transition states owing to the hydrogen bonds formation with solvent molecules is the main factor governing the direction of the reaction. Trifluoroethanol forms a strong H-bond with the carbonyl oxygen atom of the trifluoroacetyl group increasing its electrophilicity. It also solvates the departing bromide anion facilitating the occurrence of the SN2-substitution reaction. An essential but less important factor is the ability of trifluoroethanol to play the role of a nucleophilic partner by forming hydrogen bonds at the expense of the unshared electron pair of the hydroxyl oxygen facilitating the proton abstraction from the nitrogen atom of the diamine attacking the carbon atom in the course of SN2-substitution.

Reactions of α-alkoxy and α-piperidino α,β-unsaturated aldehydes with primary amines

ConclusionsThe reaction of α-alkoxyacroleins with primary amines affords only Schiff bases, αPiperidinocrotonaldehyde reacts with alkylamines, forming a mixture of 1-(alkylamino)-2piperidino-2-butene, 1,2-bis(alkylamino)-butane, and N-formylpiperidine. Their correlation is determined by the reaction conditions and by the structure of the alkylamine.

Protonation and hydrolysis of α-piperidinocrotonaldehyde

Conclusions1.Treatment of α-piperidinocrotonaldehyde with hydrogen chloride or trifluoroacetic acid gave the corresponding enammonium salt. Reaction of the aldehyde with acetic acid caused dissociation and polymerization.2.Hydration of the double bond of a-piperidinocrotonaldehyde in acid medium proceeded according to the Markownikoff rule to yield the piperidine salt and ethylglyoxal.