RESUMO
Herein, we report a facile isocoumarin and isoquinolone preparation by taking advantage of an initial bis(triflyl)ethylation [triflyl = (trifluoromethyl)sulfonyl] reaction, followed by heterocyclization, which contrasts with our previous results on cyclobutene formation. The efficiency of the catalyst- and irradiation-free heterocyclization/bis(triflyl)ethylation sequence showed exquisite dependence on the electronic nature of the substituents at the 2-ethynylbenzoate(benzamide) precursors. Molecular docking of model bis(triflyl)ethylated isocoumarins on human acetylcholinesterase (hAChE) revealed promising biological activities through selective coordination on both the catalytic active site and peripheral active site.
RESUMO
The carboarylation reaction of biphenyl-alkynes was successfully triggered by electrophilic attack of 1,1-bis(triflyl)ethylene on the alkyne moiety to give polycyclic aromatic hydrocarbons (PAHs) decorated by superacidic carbon acid functionality. Neutralisation of thus obtained acids with NaHCO3 yielded the corresponding sodium salts, which showed improved solubility in both aqueous and organic solvents.
Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Alcinos , Carbono , Ácido Carbônico , CiclizaçãoRESUMO
New azahelicenes having interesting photophysical properties have been prepared in a four-step sequence. These [7]helicenocarbazoles are efficient blue luminophores, demonstrating the utility of gold catalysis in the preparation of advanced materials.
RESUMO
The controlled metal-free preparation of fused δ-sultone derivatives has been developed starting from hydroxyallenynes. The use of 2-(3,3-diethyltriaz-1-enyl)-4-methylbenzene-1-sulfonyl chloride in a sulfonylation/rearrangement sequence gives access to 1,3-dien-2-yl arenesulfonates. These functionalized enynes suffered a direct cyclization/desaturation radical cascade, allowing the synthesis of a variety of enynyl [1,2]oxathiine 1,1-dioxides. Stereoselective cyclization of the readily formed core through intramolecular Diels-Alder reaction has also been demonstrated, affording ß-lactam- and glucofuranoside-fused δ-sultone polycycles. These selective reactions have been studied experimentally and additionally, their reaction mechanisms have been investigated computationally by means of density functional theory calculations.
RESUMO
Controlled preparation of 2,5-dihydro-1H-pyrroles, 3,6-dihydro-2H-pyrans, and pyrroles has been achieved through switchable chemo- and regioselectivity in the metal-catalyzed heterocyclization reactions of allenic amino alcohols. The gold-catalyzed cycloisomerization reaction of α-amino-ß-hydroxyallenes was effective as 5-endo cyclization by addition of amino functionality to the distal allene carbon to yield enantiopure 2,5-dihydro-1H-pyrroles, whereas their palladium-catalyzed cyclizative coupling reactions furnished 3,6-dihydro-2H-pyrans through a chemo- and regioselective 6-endo cycloetherification. Conversely, the gold-catalyzed heterocyclization reaction of ß-amino-γ-hydroxyallenes generated exclusively pyrrole derivatives. These results could be explained through a chemo- and regioselective 5-exo aminocyclization to the central allene carbon followed by aromatization. Chemo- and regioselectivity depend on both linker elongation as well as the type of catalyst. This behavior can be justified by means of density functional theory calculations.
RESUMO
Passerini (P-3CR) and Ugi (U-4CR) reactions were investigated in 4-oxoazetidine-2-carboxaldehydes, affording the corresponding Passerini and Ugi adducts with moderate diastereoselectivity in high yields. Fortunately, the obtained mixtures of isomers syn/anti were separated in most cases. The scope of both IMCRs has been studied using a variety of isocyanides, carboxylic acids and amines. Ugi adducts were used for the preparation of unusual 2-azetidinones fused to medium-sized rings via RCM. In addition, ß-lactam-diketopiperazine hybrids have also been prepared from the corresponding Ugi adducts.
Assuntos
Aldeídos/química , Aldeídos/síntese química , beta-Lactamas/química , Azetidinas/química , Técnicas de Química SintéticaRESUMO
The chemistry of allenes is an appealing topic which fascinates chemists nowadays. Their reactivity and versatility makes this skeleton a useful moiety to create a great variety of structures depending on the functional groups attached and the reaction conditions used. Recently, there is a growing interest in the study of the reactivity of bis(allenes) inspired in the chemistry developed in simple allenes. In this review a collection of examples of cyclization reactions of bis(allenes) is presented as well as the future perspectives.
RESUMO
A metal-free preparation of structurally novel bicyclic azocine-ß-lactams has been developed. The first examples accounting for the preparation of eight-membered rings from bis(allenes) in the absence of metals have been achieved by the thermolysis of nonconjugated 2-azetidinone-tethered bis(allenes) on application of microwave irradiation. This selective carbocyclization reaction has been studied experimentally, and additionally, its mechanism has been investigated by a DFT study.
Assuntos
Alcadienos/química , Azocinas/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , beta-Lactamas/síntese química , Azocinas/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Catálise , Micro-Ondas , Estrutura Molecular , Teoria Quântica , beta-Lactamas/químicaRESUMO
The organocatalyzed U-3CR of 4-oxoazetidine-2-carbaldehydes has been studied. In addition, the organocatalyzed P-3CR of 4-oxoazetidine-2-carbaldehydes and azetidine-2,3-diones has been described for the first time. U-3CR and P-3CR adducts have been obtained in good yields and reasonable diastereoselectivities. Phenyl phosphinic acid has been the catalyst of choice to study the scope of both organocatalyzed multicomponent reactions using a variety of ß-lactams, isocyanides, and amines. Highly functionalized U-3CR and P-3CR adducts derived from ß-lactams have proved to be useful substrates for the preparation of enantiopure γ-lactams and γ-lactones via N1-C2 ß-lactam ring opening/cyclization under acidic or basic conditions.
RESUMO
Passerini (P-3CR) and Passerini-Smiles reactions were investigated in azetidine-2,3-diones, affording the corresponding 3,3-disubstituted-ß-lactams with complete diastereoselectivity in high yields. The study has been carried out using different isocyanides, carboxylic acids, and phenols showing the scope of both reactions. In addition, the regioselective synthesis of highly functionalized ß-lactam-triazole hybrids has been developed via a Passerini/CuAAC sequence. Interestingly, the use of dialkynes/diazides or trialkynes/triazides as linkers in the CuAAC step has allowed the synthesis of C(2) and C(3) symmetric ß-lactam-triazole hybrids, respectively.
RESUMO
The allene moiety represents an excellent partner for the [2+2] cycloaddition with alkenes and alkynes, affording the cyclobutane and cyclobutene skeletons in a single step. This strategy has been widely studied under thermal, photochemical and microwave induced conditions. More recently, the use of transition metal catalysis has been introduced as an alternative relying on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of polycyclic compounds in a regio- and stereoselective fashion. This critical review focuses on the most recently developed [2+2] cycloadditions on allenes along with remarkable early works accounting for the mechanism, the regio- and diastereoselectivity of the cycloadducts formed (103 references).
RESUMO
Carbazoles possessing Tf2CHCH2 groups were obtained by the reaction of 1-(indol-2-yl)but-3-yn-1-ols with in situ-generated Tf2C[double bond, length as m-dash]CH2 through vicinal difunctionalisation of the alkyne moiety, where the vinyl-type carbocation intermediate was selectively attacked by the indole moiety and not by the carbanion moiety.
RESUMO
3-Substituted-3-hydroxy-beta-lactams, with two new adjacent stereogenic centers, have been prepared in a single step by a rhodium-catalyzed, three-component reaction between azetidine-2,3-diones, ethyl diazoacetate, and alcohols. Good to moderate stereoselectivity was obtained depending on the alcohol used. The stereochemistry of the new centers has been undoubtedly assigned by single crystal X-ray diffraction.
Assuntos
Álcoois/química , Azetidinas/química , Compostos de Diazônio/química , Lactamas/síntese química , Ródio/química , Catálise , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
[reaction: see text] Thermolysis of beta-lactam-tethered enallenyl alcohols gave tricyclic ring structures via a formal [2 + 2] cycloaddition of the alkene with the distal bond of the allene, while the tin-promoted radical cyclization in 2-azetidinone-tethered allenynes proceeded to provide bicyclic beta-lactams containing a medium-sized ring. The access to cyclization precursors was achieved by regio- and stereoselective metal-mediated carbonyl allenylation of 4-oxoazetidine-2-carbaldehydes in an aqueous environment.
RESUMO
A novel and direct synthetic strategy to prepare fused tricycles has been developed from monocyclic allenols, masked functionalized dienes, which underwent a domino allenol transposition/intramolecular Diels-Alder reaction.
RESUMO
4-Membered nitrogen-containing heterocycles, such as ß-lactams (ie, 2-azetidinones) and azetidines, are useful substrates in organic chemistry for the design and preparation of biologically active compounds by functionalization of the different positions of the ring. In addition, these compounds are versatile building blocks for the synthesis of other types of nitrogen-containing compounds with potential biological properties. This review summarizes recent data regarding the preparation and properties of 4-membered nitrogen-containing heterocyclic rings, as well as their biological activities.
Assuntos
Anti-Infecciosos/síntese química , Azetidinas/síntese química , Avaliação Pré-Clínica de Medicamentos/métodos , Compostos Heterocíclicos/síntese química , beta-Lactamas/síntese química , Animais , Anti-Infecciosos/farmacologia , Azetidinas/farmacologia , Química Farmacêutica/métodos , Desenho de Fármacos , Estrutura Molecular , beta-Lactamas/farmacologiaRESUMO
A novel approach to racemic and enantiopure nonconventional fused bi- and tricyclic beta-lactams has been developed by using regio- and stereocontrolled intramolecular free radical reactions in monocyclic 2-azetidinone-tethered allenynes and haloallenes. The access to allene cyclization precursors was achieved by metal-mediated carbonyl allenylation of appropriately substituted 4-oxoazetidine-2-carbaldehydes in an aqueous environment. The tin-promoted radical cyclizations of allene-beta-lactams are totally regioselective for the central allenic carbon, providing bi- and tricyclic beta-lactams containing a seven-membered ring.
Assuntos
beta-Lactamas/síntese química , Ciclização , Radicais Livres , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Conformação Molecular , Compostos Orgânicos de Estanho/química , Estereoisomerismo , Estanho/químicaRESUMO
A convenient metal-free methodology for the preparation of structurally novel, strained tricyclic beta-lactams containing a cyclobutane ring has been developed. The first examples accounting for the intramolecular [2+2] cycloaddition reactions in beta-lactams have been achieved by the thermolysis of 2-azetidinone-tethered enallenols, which have been prepared in aqueous media by regio- and diastereoselective indium-mediated carbonyl allenylation of 4-oxoazetidine-2-carbaldehydes. Notably, the regioselectivity of the cycloaddition can be tuned in the allene component just by a subtle variation in the substitution pattern of the alkene component.
Assuntos
Alcenos/química , Azetidinas/química , Ciclobutanos/química , beta-Lactamas/síntese química , Naftalenos/químicaRESUMO
A remarkable reaction of azetidine-2,3-diones with primary as well as secondary amines, and water is presented. Simply by varying the nucleophile, an unprecedented one-step synthesis of alpha-amino acids, alpha-amino amides, and dipeptides, was developed in both the racemic and optically pure forms. The current mechanistic hypothesis invokes a concerted process involving CO extrusion. However, a stepwise pathway can also account for these novel transformations.