RESUMO
An efficient protocol for the synthesis of stable 2-azaallyl anion salts by the reaction of alkyl 2-bromo-2H-azirine-2-carboxylates with trimethylsilyl cyanide/Bu4NF has been developed. The domino reaction proceeds in four steps via the cleavage of the azirine C-C bond to provide the tetrabutylammonium salts of stereochemically pure 2-azaallyl anions having U-configuration relative to the cyano groups. The anions with an ortho-substituted aryl group or styryl group exist as a mixture of two geometrical isomers across the N2-C3 bond. 2-Azaallyl anion salts have been shown to be convenient substrates for the one-pot synthesis of densely functionalized 2H-pyrroles by the alkylation-cyclization sequence.
RESUMO
An efficient one-pot synthesis of imidazo[1,2-a]pyridines from 2-bromoazirines and pyridines has been developed. The construction of the bicyclic framework of imidazo[1,2-a]pyridines occurs in two steps through the formation of (2H-azirin-2-yl)pyridinium bromides followed by dehydrobrominative UV light-induced cyclization. The method can also be applied for the synthesis of imidazo[2,1-a]isoquinolines. Unstable in solution, (2H-azirin-2-yl)pyridinium/isoquinolinium bromides were quantitatively converted to stable tetrafluoroborates, which can be cyclized to imidazo[1,2-a]pyridines under UV irradiation in the presence of bromide ions.
RESUMO
A high yield synthesis of 2-amino-4-pyrrolin-3-ones including 4-pyrrolin-3-one-based amino esters by the NBS- or TfCl-mediated reaction of 3-hydroxypyrroles with amines has been developed. The reaction of 3-hydroxypyrroles with triflyl chloride in the absence of amine affords 2,2'-bi(4-pyrrolin-3-ones) in excellent yields and diastereoselectivity. The relative configuration of stereocenters in these compounds can be changed from (2RS,2'RS) to (2RS,2'SR) by the action of NaH in THF, while the reverse stereoisomerization occurs in the presence of 2,5-lutidine in MeCN. Bi(4-pyrrolin-3-ones) also can be converted to 2-amino-4-pyrrolin-3-ones in excellent yields. Bi(4-pyrrolin-3-ones) and 2-amino-4-pyrrolin-3-ones were evaluated for their antiproliferative activity toward four human tumor cell lines.
Assuntos
Aminas , Ésteres , HumanosRESUMO
A domino synthesis of dispiro-fused N-vinyl ß-lactams from diazo-Meldrum's acid and 2H-azirines or 5-alkoxyisoxazoles via the "2-azabuta-1,3-diene formation/Staudinger ketene-imine cycloaddition" sequence is described. The Rh2(Piv)4-catalyzed formation of the 2-azabuta-1,3-diene intermediates in the first stage of the reaction sequence proceeds via addition of the rhodium carbenoid to the azirines/isoxazoles and provides the first example of the generation of iminium-type ylides from diazo-Meldrum's acid. This methodology was extended to monospiro-ß-lactams, which were synthesized in two steps using acyclic α-diazocarbonyl compounds in the stage of the formation of 2-azabuta-1,3-dienes. The method allows for the rapid assemblage of the carbon part of the azetidin-2-one system from diazo compounds only and affords spiro- and dispiro-ß-lactams in moderate yields. A bromine atom in the 2-bromoalkenyl moiety of the synthesized ß-lactams can be easily substituted by hydrogen under catalytic hydrogenation conditions or by 2-pyridyl-substituent via the Stille cross-coupling reaction.
RESUMO
An effective and operationally simple method for the preparation of methyl 2-(di/tri/tetraazol-1-yl)-2 H-azirine-2-carboxylates from accessible methyl 2-halo-2 H-azirine-2-carboxylates and NH-azoles has been developed. The azoles having enhanced NH acidity, react with 2-halo-2 H-azirines in the presence of Et3N in a deprotonated form, while the azoles having highly nucleophilic sp2 nitrogen react in neutral form. According to the DFT calculations, the substitution of the halogen by the azole proceeds via an SN2'-SN2' cascade, with the initial conjugate substitution of the halogen being the rate-determining step. The formation of 2,3-dipyrazolylaziridines in the reaction of pyrazole provides experimental evidence for the cascade mechanism of the reaction.
RESUMO
Various 2-oxygen-substituted 2H-azirine-2-carboxylic acid derivatives were synthesized in high yields under mild conditions from readily available precursors, 2-halo-2H-azirines and OH-reagents having pKa values in the range of 3-10. This reaction is the first example of substitution at the azirine carbon atom for which an unusual SN2'-SN2' cascade mechanism was revealed.
RESUMO
4-Aminopyrrole-3-carboxylates and pyrazine-2-carboxylates were synthesized from 5-alkoxyisoxazoles and 1-sulfonyl-1,2,3-triazoles by tuning the Rh(II) catalyst and the reaction conditions. The reaction in chloroform at 100 °C under Rh2(OAc)4 catalysis provides 4-aminopyrrole-3-carboxylates in good yields. The use of Rh2(Piv)4 in refluxing toluene results in the formation of 1,2-dihydropyrazine-2-carboxylates as the main products, which can be converted by a one-pot procedure to pyrazine-2-carboxylates by heating with catalytic amounts of TsOH. According to the NMR and DFT investigations of the reaction mechanism, pyrroles and dihydropyrazines are formed, respectively, via 1,5- and 1,6-cyclization of common (5Z)-1,4-diazahexa-1,3,5-triene intermediates. The influence of the nature of the catalyst on the product distribution is rationalized in terms of the Rh-catalyzed isomerization of a pyrrolin-2-ylium-3-aminide zwitterion, the primary product of 1,4-diazahexatriene 1,5-cyclization.
RESUMO
A general and concise approach to thermally and hydrolytically stable alkyl 2,3-dihydroazete-2,3-di-/2,2,3-tricarboxylates from alkyl 2-bromoazirine-2-carboxylates or 4-bromo-5-alkoxyisoxazoles is reported. The synthesis involves the formation of 2-azabuta-1,3-diene by the reaction of rhodium carbenoid with isoxazole or azirine followed by cyclization/hydrodebromination cascade. The latter reaction is the first example of the selective hydrodehalogenation of a valence isomer under equilibrium conditions. In vitro cytotoxicity tests on THP-1 cell line revealed that the 2,3-dihydroazetes greatly differ in their ability to induce apoptosis and/or necrosis. To adequately describe and quantitatively assess these properties, the difference between the two areas under the curves of concentration dependency of apoptosis/necrosis induction within the concentration range was used. Trimethyl 4-phenyl-2,3-dihydroazete-2,2,3-tricarboxylate was found to display the maximal apoptotic potential coupled with high cytotoxic and minimal necrotic potential.
RESUMO
The three-membered ring in 2-(2-pyridyl)azirine-2-carboxylic esters and thioesters can undergo selective cleavage of either the N-C2 bond under copper(II) catalysis or the C-C bond under the action of HCl to provide isomeric azirine ring expansion products of pyrazolo[1,5-a]pyridine or imidazo[1,5-a]pyridine series, respectively. Mild catalytic reaction conditions for the formation of pyrazolopyridines make it possible to obtain them directly from 4-bromoisoxazoles by a one-pot, three-stage procedure without isolating the intermediate 2-bromoazirines and 2-(2-pyridyl)azirines.
RESUMO
A high-yield method for the introduction of a 2-pyridyl substituent in the C2 position of the three-membered ring of 2-bromo-2H-azirine-2-carboxylic acid derivatives by the direct cross-coupling with 2-(trialkylstannyl)pyridines has been described. The reaction works well with 3-, 4-, or 5-substituted 2-stannylpyridines and can be also employed for the synthesis of 2-(thiazol-2-yl)-2H-azirines. According to DFT calculations, the reaction proceeds through the sequence of SN2'-substitution of bromine, 1,4-stannyl shift, and [2,3]-sigmatropic shift of the pyridine ring.