RESUMO
The first ruthenium-catalyzed carboamination of olefins with α-carbonyl sulfoxonium ylides is reported. The utilization of an inexpensive ruthenium catalyst enables the concise synthesis of pharmaceutically important isoindolin-1-ones, which possess both a stereogenic center and ß-carbonyl side chain. This method is mild, efficient, and scalable and allows for the coupling of a wide range of aryl-, heteroaryl-, alkenyl-, and alkyl-substituted sulfoxonium ylides. Moreover, the carbonyl side chain in the resulting product provides a good handle for downstream transformations. For mechanistic studies, a ruthacyle complex is obtained and proven to be the key intermediate in both catalytic and stoichiometric reactions.
RESUMO
To date, it remains challenging to achieve a general and catalytic α-arylation of cyclic 1,3-dicarbonyls, particularly ubiquitous heteroaromatic ones. In most cases, the preparation of their medically significant arylated derivatives requires multistep synthetic sequences. Herein, we introduce a new, convenient strategy involving the conversion of cyclic 1,3-dicarbonyls to cyclic iodonium ylides (CIYs), followed by rhodium-catalyzed α-arylation with arylboronic reagents via carbene coupling. This approach is mild, operationally simple, base-free, biocompatible, and exhibits broad substrate scope (>100â examples), especially with respect to various heteroaromatic 1,3-dicarbonyls and ortho-substituted or base-sensitive arylboronic acids. Importantly, owing to the excellent compatibility with various arylboronic acids or boronate esters (ArBpin, ArBneop, or ArBF3K), this method allows the late-stage installation of heterocyclic 1,3-dicarbonyl motifs in highly complex settings. The utility of this transformation is further demonstrated through significantly simplifying the synthesis of several bioactive molecules and natural products.
RESUMO
Six new aromatic acids (1-6) and three new leucine derivatives containing an unusual oxime moiety (7-9) were isolated and identified from the deep-sea-derived actinomycetes strain Streptomyces chumphonensis SCSIO15079, together with two known compounds (10-11). The structures of 1-9 including absolute configurations were determined by detailed NMR, MS, and experimental and calculated electronic circular dichroism spectroscopic analyses. Compounds 1-9 were evaluated for their antimicrobial and cytotoxicity activities, as well as their effects on intracellular lipid accumulation in HepG2 cells. Compounds 3 and 4, with the most potent inhibitory activity on intracellular lipid accumulation at 10 µM, were revealed with potential antihyperlipidemic effects, although the mechanism needs to be further studied.
Assuntos
Actinobacteria , Actinomyces , Dicroísmo Circular , Hipolipemiantes/farmacologia , Leucina , Lipídeos , Estrutura MolecularRESUMO
An expedient strategy for the synthesis of 5-oxazole ketones was developed via homogeneous gold catalysis with 4-MeO-TEMPO as an oxidant. The desired 5-oxazole ketones were achieved in decent yields with an excellent functional group compatibility under mild conditions. The current protocol also represents the first example for merging a gold catalyst and radical chemistry in one-pot synthesis with internal N-propargylamides.
RESUMO
An efficient and convenient synthesis of valuable disulfanes and benzenesulfonothioates, having a 2-aminofuran framework, has been developed by employing a copper-catalyzed transformation of readily available N-tosylhydrazone-bearing thiocarbamates. This method features an inexpensive metal catalyst, mild reaction conditions, good functional-group tolerance, short reaction times, and delivers valuable and complex products. A copper carbene generated from an N-tosylhydrazone-bearing thiocarbamate is proposed as the key intermediate for the transformation and it triggers the subsequent cascade. Remarkably, the Ts anion released from N-tosylhydrazone further serves as a nucleophile, thus rendering the formation of benzenesulfonothioates under controlled conditions.
RESUMO
An unprecedented substituent-controlled chemoselective cleavage of CâC double bond or C(sp(2))-C(CO) bond along with aerobic phosphorylation of α,ß-unsaturated carbonyl compounds with H-phosphonates through a radical process has been disclosed. The current strategy provides an access to ß-ketophosphonates under mild conditions with a wide substrate scope.
RESUMO
C-N bond formation via a copper-catalyzed aerobic oxidative decarboxylative tandem protocol was realized. The phenylacetic acids which contain ortho-X (X = F or Br) on the aromatic ring will render a fused five-membered heterocycle via a tandem aromatic nucleophilic substitution and aerobic oxidative decarboxylative acylation at the C(sp(2))-H bond of benzimidazoles under the Cu(OAc)2/K2CO3/BF3·Et2O catalytic system, while with CuBr as the catalyst and pyridine as the base, N-acylation occurred and tertiary amides were obtained.
RESUMO
A copper-catalyzed oxidative direct formation of amides from nonactivated carboxylic acids and azoles with dioxygen as an activating reagent is reported. The azole amides were produced in good to excellent yields with a broad substrate scope. The mechanistic studies reveal that oxygen plays an essential role in the success of the amidation reactions with copper peroxycarboxylate as the key intermediate. Transamidation occurs smoothly between azole amide and a variety of amines.
RESUMO
To date, the general and catalytic α-arylation of cyclic 1,3-dicarbonyls remains elusive. We now report the first Rh-catalyzed α-arylation of cyclic 1,3-dicarbonyls with benzocyclobutenols through a cyclic iodonium ylide strategy. Our strategy represents a good solution for the previously challenging α-arylation of cyclic 1,3-dicarbonyls with sterically demanding aryl partners, which is especially appropriate for structurally unique heteroaromatic 1,3-dicarbonyls. Our approach features mild conditions, readily available starting materials, high yields, excellent functional group-tolerance, and simple operation, providing expedient access toward medically important 2-aryl (hetero)cyclic 1,3-dicarbonyls. The practicality of this approach is demonstrated by the gram-scale synthesis, one-pot synthesis, and numerous downstream transformations.
RESUMO
Herein, we introduce an iodonium ylide strategy to achieve novel α-alkylation of cyclic 1,3-dicarbonyls through harnessing C(sp3)-Rh species generated from 5-exo-trig cyclization to provide rapid access to molecular hybridization of medically important isoindolin-1-ones and cyclic 1,3-dicarbonyls from readily available substrates. This approach features mild conditions, good yield, excellent functional group tolerance, and the simultaneous formation of two new chemical bonds and one stereogenic center. Moreover, the hydroxyl group of resulting product provides a good handle for downstream transformations. Importantly, we also demonstrate this strategy can be achieved in a one-pot manner. A C(sp3)-Rh complex was prepared and proved to be the key intermediate.
RESUMO
A novel strategy for the synthesis of imidazo-fused polycyclic compounds under mild, base-free, and silver-free conditions by a rhodium(III)-catalyzed C-H annulation of alkenyl or arylimidazoles and (hetero)cyclic 1,3-dicarbonyl compounds is reported here. Such a step-economic protocol features the selective cleavage of two different C-H bonds in one step, featuring easy operation, readily available starting materials, gram-scale synthesis, broad functional group tolerance, and no requirement to presynthesize carbene precursors. Notably, the synthetic potential is showcased by the structural modification of drug and the highly step-economic synthesis of Janus kinase inhibitor in only three steps with a satisfactory 26% total yield (previous method: in nine steps with 0.6% yield).
Assuntos
Compostos Policíclicos , Ródio , Catálise , Ródio/químicaRESUMO
Three new derivatives of tetrahydrocurcumin 6, 7 and 9 have been prepared as potent antitumor agents using copper(II)-catalyzed 'click chemistry'. Their structures were identified using 1H-NMR, 13C-NMR and HRMS techniques. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay has been carried out to investigate the in vitro cytotoxicity against human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2) and human colon carcinoma (HCT-116). Compound 6 has showed significant inhibitory activity against HCT-116 cell line with an IC50 value of 17.86 µM compared to tetrahydrocurcumin (50.96 µM) and positive control etoposide (19.48 µM) while showed no inhibitory activity against NCM460 cell line. Compounds 7 showed moderate inhibitory activity compared to tetrahydrocurcumin and etoposide while compound 9 showed no obvious inhibitory activity. The results suggested further structure modifications of tetrahydrocurcumin to improve its anticancer activity.[Formula: see text].
Assuntos
Antineoplásicos , Carcinoma , Antineoplásicos/química , Linhagem Celular Tumoral , Cobre , Curcumina/análogos & derivados , Ensaios de Seleção de Medicamentos Antitumorais , Etoposídeo , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Inspired by the body circulation of Omeprazole (irreversible proton pump inhibitor), we disclose the carbene-triggered cascades for the synthesis of 2-aminobenzofuran derivatives from N-sulfonyl-1,2,3-triazoles or benzothioazole-bearing thiocarbamates, which represents an unprecedented imine derivative migration process. Furthermore, the desulfurizing reagent-free Barton-Kellogg-type reactions starting from N-sulfonyl-1,2,3-triazoles have also been achieved for the first time, and elemental sulfur is confirmed as a byproduct during this transformation. Both experimental data and DFT calculations further thoroughly explained the unique reactivity.
Assuntos
Iminas/química , Metano/análogos & derivados , Tiocarbamatos/química , Biomimética , Metano/química , Estrutura Molecular , Triazóis/químicaRESUMO
An important framework of o-amino benzofuranthioethers was constructed by Cu-catalyzed arylative cyclization of N-tosylhydrazone-bearing thiocarbamates with silylaryl triflates or ArI. This transformation provides a novel strategy for the synthesis of valuable arylative o-amino benzofuranthioethers in moderate yields which could not be obtained from known methods. The reaction features smart design, efficient construction, and mild reaction conditions.
RESUMO
Anti-vicinal diboronates were fabricated from easily available diarylethynes and B2pin2 via a base-catalyzed domino-borylation-protodeboronation (DBP) strategy under transition-metal-free conditions. Under the standard conditions, reactants with a range of different classes of functional groups on the rings, such as MeO, MeS, CF3O, Me2N, TMS, I, Br, Cl, F, and the thiophene ring, were tolerated. Downstream transformation of the vicinal diboronates provided a facile pathway for obtaining vicinal diols by mild oxidation with NaBO3, and a new deuteriation technique was developed in order to acquire 1,2-diarylethanes-1,2-d2 and 1,2-diarylethanes-1,1,2,2-d4. The new deuteriation strategy developed in this study may provide a new research direction for deuteriation chemistry.
RESUMO
Cross-coupling reactions involving metal carbene intermediates play an increasingly important role in C-C bond formation. Expanding the carbene precursors to a broader range of starting materials and more diverse products is an ongoing challenge in synthetic organic chemistry. Herein, we report a Suzuki-Miyaura coupling reaction of in situ-generated Pd-carbene complexes via desulfurization of thioureas or thioamides. This strategy enables the preparation of a broad array of substituted amidinium salts and unsymmetrical diaryl ketones. The reaction is readily scalable, compatible with bromo groups on aromatic rings, tolerant to moisture and air and has a broad substrate scope. Furthermore, a single crystal structure of Pd-diaminocarbene complex is obtained and proven to be the key intermediate in both catalytic and stoichiometric reactions. Preliminary mechanistic studies demonstrate the dual role of the silver salt as a desulfurating reagent assisting the elimination of sulfur and as oxidant facilitating the PdII/Pd0/PdII catalytic cycle.
RESUMO
Rhodium(ii)/phosphine-cocatalyzed bis-sulfuration of α-diazocarbonyl compounds using thiosulfonates as the sulfenylating agent, which provided two sulfur-containing moieties, was developed via simultaneous inter- and intra-molecular C-S bond formation. This novel protocol provides a rapid synthetic route to dithioketal derivatives in moderate to good yields in an atom-economic process. The transformation is proposed to proceed through phosphine ylide formation followed by S(O2)-S bond cleavage and rearrangement.
RESUMO
A palladium-catalyzed dual ortho C-H bond activation of aryl thiocarbamates is developed. This tandem reaction initiates by thiocarbamate-directed ortho C-H palladation, which leads to favorable olefin insertion rather than reductive elimination. The oxidative Heck reaction followed by another C-H activation and sulfuration affords the dual-functionalized products. This reaction provides a concise route to the S,O,C multisubstituted benzene skeleton which could be successfully applied for the synthesis of a COX-2 inhibitor.
Assuntos
Tiocarbamatos/química , Alcenos , Catálise , Inibidores de Ciclo-Oxigenase 2 , Estrutura Molecular , PaládioRESUMO
An unprecedented Cu-catalyzed oxidative cleavage of two C-N bonds of 3-aminoindazoles is reported herein, which represents the first example for denitrogenative ring-opening of 3-aminoindazoles. This novel reactivity of 3-aminoindazoles enables the production of diverse aromatic nitrile-containing (hetero)arenes via C-H arylation of (hetero)arenes with wide subsrate scope under mild conditions.
RESUMO
An efficient one-pot cascade process via unprecedented quadruple cleavage of BrCF2COOEt with primary amines to afford valuable fluorine-containing heterocycles is described, in which BrCF2COOEt plays a dual role as a C1 synthon and a difluoroalkylating reagent for the first time. Mechanistic studies supported by DFT calculations suggest that a base plays an active role in the formation of the key intermediate isocyanides generated in situ from primary amines and difluorocarbene.