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Transition metal-catalyzed divergent synthesis through alternation of the catalyst is appealing, as it provides an operationally simple way to access different valuable products, while using the same reactants as starting materials. Herein, a gold-catalyzed cascade reaction of conjugated diynamides with allylic alcohols is described. By variation of the catalysts, substituted allenes and furans could be obtained selectively. Mechanistic studies indicate that, after the addition of allylic alcohol to gold-activated diynamide, a [3,3]-sigmatropic rearrangement would take place and lead to the formation of a common reactive intermediate, which would further convert to the final products selectively. Further variation of the structure of diynamides has unveiled an additional reaction sequence involving intramolecular Himbert arene/allene Diels-Alder cycloaddition to afford a series of dearomatized products bearing bicyclo[2,2,2]octadiene core.
Assuntos
Ouro , Propanóis , Ouro/química , CatáliseRESUMO
Sulfuryl chlorofluoride was first employed as a versatile reagent for controllable chlorination and chlorooxidation of simple unprotected indoles. Three types of products including 3-chloro-indoles, 3-chloro-2-oxindoles, and 3,3-dichloro-2-oxindoles could be selectively obtained in good to excellent yields by switching the reaction solvents. The present method features easy-to-operate, broad substrate scope, and mild reaction conditions.
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An unexpected deprotonative process of thiirenium ions is presented, which provides a new synthesis of aryl thioalkynes directly from terminal alkynes via the electrophilic activation of the carbon-carbon triple bonds. The conditions are well compatible with various functional-group-substituted aryl alkynes. The direct elimination from the thiirenium ion intermediate, or its tautomer, benzyl vinyl carbocation, is supported by control experiments and labeling reaction.
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A new metal-free synthesis of pyrrole from allyl ketone and amine has been established. The reaction proceeds via an thiolative activation of the C-C double bond with dimethyl(methylthio)sulfonium trifluoromethanesulfonate, followed by a nucleophilic ring-opening addition of primary amine to the generated episulfonium intermediate, and then an internal condensation and aromatization. This mild procedure provides a novel strategy to the construction of substituted pyrroles through a formal [4 + 1] cycloaddition reaction.
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A novel synthesis of 2-(cyanomethyl)benzoic esters from indanone derivatives has been established. This reaction proceeds via a deprotonation of alcohols with a chemical base, followed by a nucleophilic addition to indanones and Beckmann fragmentation. In addition, this reaction could also work under electrochemical conditions, and no external chemical bases were needed. This mild method offers a novel strategy for the late-stage functionalization of various natural alcohols.
Assuntos
Carbono , Ésteres , Ácido Benzoico , IndanosRESUMO
Radical fluorosulfonylation is emerging as an appealing approach for the synthesis of sulfonyl fluorides, which have widespread applications in many fields, in particular in the context of chemical biology and drug development. Here, we report the first investigation of FSO2 radical generation under electrochemical conditions, and the establishment of a new and facile approach for the synthesis of ß-keto sulfonyl fluorides via oxo-fluorosulfonylation of alkynes with sulfuryl chlorofluoride as the radical precursor and air as the oxidant. This electrochemical protocol is amenable to access two different products (ß-keto sulfonyl fluorides or α-chloro-ß-keto sulfonyl fluorides) with the same reactants. The ß-keto sulfonyl fluoride products can be utilized as useful building blocks in the synthesis of various derivatives and heterocycles, including the first synthesis of an oxathiazole dioxide compound. Furthermore, some ß-keto sulfonyl fluorides and derivatives exhibited notably potent activities against Bursaphelenchus xylophilus and Colletotrichum gloeosporioides.
Assuntos
Alcinos/química , Sulfonas/síntese química , Animais , Anti-Helmínticos/farmacologia , Antifúngicos/farmacologia , Colletotrichum/efeitos dos fármacos , Técnicas Eletroquímicas , Rabditídios/efeitos dos fármacos , Sulfonas/farmacologiaRESUMO
An environmentally benign method for the synthesis of aryl sulfides in water under mild conditions has been realized, in which arenes are coupled with equal stoichiometry of allyl sulfides. This arylthiolation is enabled by the presence of the Lipshutz surfactant, TPGS-750-M, using water as the recyclable reaction medium.
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The proanthocyanidins from ethanol extracts (80%, v/v) of Acacia mearnsii (A. mearnsii) bark on chemical-based and cellular antioxidant activity assays as well as carbolytic enzyme inhibitory activities were studied. About 77% of oligomeric proanthocyanidins in ethanol extracts of A. mearnsii bark were found by using normal-phase HPLC. In addition, HPLC-ESI-TOF/MS and MALDI-TOF/TOF MS analyses indicated that proanthocyanidins from A. mearnsii bark exhibited with a degree of polymerization ranging from 1 to 11. These results of combined antioxidant activity assays, as well as carbolytic enzyme inhibitory activities of proanthocyanidins from A. mearnsii bark, indicated an encouraging antioxidant capacity for the high polyphenol content and a potential for use as alternative drugs for lowering the glycemic response.
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Acacia/química , Antioxidantes/química , Etanol/química , Hipoglicemiantes/química , Casca de Planta/química , Extratos Vegetais/química , Proantocianidinas/química , Cromatografia Líquida de Alta Pressão , Células Hep G2 , Humanos , Polifenóis/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
A new protocol for achieving the phosphination of arenes, arenols and thiols has been disclosed. This chemistry, in which diaryl(((trifluoromethyl)sulfonyl)oxy)phosphines as a kind of electrophilic phosphination reagents are in situ generated from diarylphosphine oxides, provides an efficient and mild approach for the synthesis of aromatic organophosphorus compounds.
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Cationic palladium(II) complexes have been found to be highly reactive towards aromatic C-H activation of arylureas at room temperature. A commercially available catalyst [Pd(MeCN)4](BF4)2 or a nitrile-free cationic palladium(II) complex generated in situ from the reaction of Pd(OAc)2 and HBF4, effectively catalyzes C-H activation/cross-coupling reactions between aryl iodides, arylboronic acids and acrylates under milder conditions than those previously reported. The nature of the directing group was found to be critical for achieving room temperature conditions, with the urea moiety the most effective in promoting facile coupling reactions at an ortho C-H position. This methodology has been utilized in a streamlined and efficient synthesis of boscalid, an agent produced on the kiloton scale annually and used to control a range of plant pathogens in broadacre and horticultural crops. Mechanistic investigations led to a proposed catalytic cycle involving three steps: (1) C-H activation to generate a cationic palladacycle; (2) reaction of the cationic palladacycle with an aryl iodide, arylboronic acid or acrylate, and (3) regeneration of the active cationic palladium catalyst. The reaction between a cationic palladium(II) complex and arylurea allowed the formation and isolation of the corresponding palladacycle intermediate, characterized by X-ray analysis. Roles of various additives in the stepwise process have also been studied.
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An asymmetric Brønsted acid catalyzed dearomatizing redox cross coupling reaction has been realized, in which aryl hydrazines react with ketones to deliver 1,4-diketones, bearing an all-carbon quarternary stereocenter in high enantiopurity.
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Indole motifs are important heterocycles found in natural products, pharmaceuticals, agricultural chemicals, and materials. Although there are well-established classical name reactions for indole synthesis, these transformations often require harsh reaction conditions, have a limited substrate scope, and exhibit poor regioselectivity. As a result, organic synthesis chemists have been exploring efficient and practical methods, leading to numerous strategies for synthesizing a variety of functionalized indoles. In recent years, electrochemistry has emerged as an environmentally friendly and sustainable synthetic tool, with widespread applications in organic synthesis. This technology allows for elegant synthetic routes to be developed for the construction of indoles under external oxidant-free conditions. This feature article specifically focuses on recent advancements in indole synthesis from non-indole-based substrates, as well as the mechanisms underlying these transformations.
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We disclose a deconstructive [5 + 1] annulation protocol for the synthesis of isoquinolones through a nitrogen insertion into abundant indanones. This method exploits photoredox-catalyzed ring-opening of oxime esters. The reaction proceeds smoothly with water as the reaction medium and tolerates a range of functional groups on diverse thiophenols, amines, or indanones. Moreover, the representative isoquinolones exhibit promising antifungal activities.
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A visible-light-mediated catalyst- and additive-free method for radical ring-opening fluorosulfonylation of methylenecyclobutanols is reported. Sulfuryl chlorofluoride acts as a FSO2 radical precursor as well as an electron acceptor to form electron donor-acceptor complexes with various methylenecyclobutanol substrates. This method shows fully regioselective and (E)-stereoselective ring-opening processes, providing a variety of FSO2-functionalized γ,δ-unsaturated carbonyls in 38-77% yields. A selection of product diversifications has been studied to demonstrate the versatility of these sulfonyl fluoride products.
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An electrochemical method is presented to construct 1,3-oxazines by the oxidative ring-opening of cyclopropylamides with alcohols. This method avoids the use of external oxidants and thus shows good functional group tolerance. The substrate scope covers primary, secondary, and tertiary alcohols as well as (hetero)aryl amide-substituted cyclopropanes.
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An electrochemical approach to biheteroaryls through the coupling of diverse N-heteroarenes with heteroaryl phosphonium salts is reported. The reaction features pH and redox-neutral conditions and excellent regioselectivity, as well as exogenous air or moisture tolerance. Additionally, a one-pot, two-step protocol can be established to realize formal C-H/C-H coupling of heteroarenes, thereby greatly expanding the substrate availability. The utility of this method is demonstrated through late-stage functionalization, the total synthesis of nitraridine, and antifungal activity studies.
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A radical hydro-fluorosulfonylation of propargyl alcohols with FSO2Cl is presented based on the photoactivation of the electron donor-acceptor (EDA) complex. The reaction avoids the requirement for photocatalysts, bases, hydrogen donor reagents, any other additives, and harsh conditions, enabling the facile synthesis of various functionalized γ-hydroxy (E)-alkenylsulfonyl fluorides. These multifunctional sulfonyl fluorides can be further diversified, providing access to various privileged molecules of biological relevance.
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The selective hydrodeoxygenation (HDO) of lignin-derived methoxyphenols to cyclohexanol is one of the most significant transformation in biomass conversion since cyclohexanol is an important industrial raw material. This study has disclosed a series of tungstated zirconia with different Zr/W ratio supported Ru catalysts (Ru/xZrW, x means the molar ration of Zr/W) for the hydrodeoxygenation (HDO) of guaiacol to cyclohexanol. Among these catalysts, Ru/16ZrW has the best catalytic activity, which can achieve 92% yield of cyclohexanol under the conditions of 180 oC and 1 MPa H2 pressure for 2 h (TOF 231 h-1). Compared with Ru/ZrO2, Ru/16ZrW has smaller particles, more dispersed and electron-rich Ru species, significant hydrogen spillover and more acid sites, which are the main reason for its excellent performance on this reaction. Apart from guaiacol, other methoxy substitution phenols and organosolv lignin can also be converted into cyclohexanol via hydrodeoxygenation reactions over this catalyst.
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A radical fluorosulfonyl arylation of alkynes with sulfuryl chlorofluoride as the FSO2 radical precursor via electron donor-acceptor photoactivation driven by daylight or a blue light-emitting diode is disclosed. A series of valuable benzo-fused carbocycles and heterocycles have been produced with simple operation under mild conditions in the absence of any external catalysts or additives. The synthetic potential of this protocol has further demonstrated excellent scalability, as well as diverse postderivatizations, including SuFEx reactions and other useful cascade reactions.
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Mutations within the oncogene KRAS drive an estimated 25% of all cancers. Only allele-specific KRAS G12C inhibitors are currently available and are associated with the emergence of acquired resistance, partly due to upstream pathway reactivation. Given its upstream role in the activation of KRAS, son of sevenless homolog 1 (SOS1), has emerged as an attractive therapeutic target. Agents that target SOS1 for degradation could represent a potential pan-KRAS modality that may be capable of circumventing certain acquired resistance mechanisms. Here, we report the development of two SOS1 cereblon-based bifunctional degraders, BTX-6654 and BTX-7312, cereblon-based bifunctional SOS1 degraders. Both compounds exhibited potent target-dependent and -specific SOS1 degradation. BTX-6654 and BTX-7312 reduced downstream signaling markers, pERK and pS6, and displayed antiproliferative activity in cells harboring various KRAS mutations. In two KRAS G12C xenograft models, BTX-6654 degraded SOS1 in a dose-dependent manner correlating with tumor growth inhibition, additionally exhibiting synergy with KRAS and MEK inhibitors. Altogether, BTX-6654 provided preclinical proof of concept for single-agent and combination use of bifunctional SOS1 degraders in KRAS-driven cancers.