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A reaction for H-F bond insertion into α-diazo carbonyl compounds is reported. The protocol describes a simple reaction setup employing commercially available HF·pyr (Olah reagent) as the fluorine source. The method is rapid and practical, and allows access to a broad range of α-fluorinated carbonyl compounds in generally good yields.
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Compostos Azo , Flúor , Compostos Azo/química , Catálise , Flúor/químicaRESUMO
Covering: 2017-2019Guanidine natural products isolated from microorganisms, marine invertebrates and terrestrial plants, amphibians and spiders, represented by non-ribosomal peptides, guanidine-bearing polyketides, alkaloids, terpenoids and shikimic acid derived, are the subject of this review. The topics include the discovery of new metabolites, total synthesis of natural guanidine compounds, biological activity and mechanism-of-action, biosynthesis and ecological functions.
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Anuros/metabolismo , Bactérias/metabolismo , Produtos Biológicos/química , Fungos/metabolismo , Guanidinas/metabolismo , Animais , Organismos Aquáticos/química , Organismos Aquáticos/metabolismo , Bactérias/química , Bactérias/genética , Produtos Biológicos/metabolismo , Fungos/química , Invertebrados/química , Invertebrados/metabolismo , Estrutura Molecular , Plantas/química , Plantas/metabolismo , Saxitoxina/química , Saxitoxina/metabolismo , Metabolismo Secundário , Aranhas/química , Aranhas/metabolismo , Tetrodotoxina/química , Tetrodotoxina/metabolismoRESUMO
Two visible-light-mediated O-H insertion protocols involving oximes and aryldiazoacetates leading to different products depending on the solvent employed are reported. In DCM, direct O-H insertion takes place. In THF, there is the additional incorporation of the ring-opened form of this solvent into the structure of the product. These metal-free protocols are mild and tolerant to air and moisture. The preparation of an acaricide has been developed as an example of synthetic application.
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Éteres , OximasRESUMO
Carbenes are important intermediates in organic chemistry and have been widely applied in various types of organic reactions, ranging from cycloaddition reactions and sigmatropic rearrangements to C-H functionalizations, thus allowing the rapid construction of densely functionalized molecules. Over the past decades, remarkable progress has been achieved in metal-catalyzed carbene transfer reactions. Nevertheless, realizing these transformations under milder and/or greener conditions is still highly desirable. Only recently, visible light-promoted carbene transfer reactions of diazo compounds via free carbene intermediates have emerged as a practical, mild and powerful tool. In this tutorial review, we summarize the latest advances in the area, aiming at providing a clear overview on reaction design, mechanistic scenarios and potential future developments.
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A visible-light-promoted photochemical protocol is reported for the coupling of aryldiazoacetates with boronic acids. This photochemical reaction shows great enhancement compared to the same protocol performed in the absence of light. Except for a few cases, the room temperature coupling in the dark (thermal process) generally does not work. When it does, it is likely to also involve free carbenes as key intermediates. Alternatively, photochemical reactions show a broad scope, can be performed under air and tolerate a wide variety of functional groups. Reaction-evolution monitoring, DFT calculations and control experiments have been used to evaluate the main aspects of this intricate mechanistic scenario. Biologically active molecules Adiphenine, Benactyzine and Aprophen have been prepared as examples of synthetic applications.
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A two-step reaction sequence is described for the asymmetric formal α-propargylation of ketones. This approach takes advantage of an aminocatalyzed conjugate addition of ketones to alkylidene isoxazol-5-ones, followed by a controlled nitrosative degradation event. The target compounds can be accessed in broad scope, in moderate to good yields, perfect diastereocontrol and good to excellent enantioselectivity.
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A novel, scalable strategy for the preparation of 2,3,4,6-tetrasubstituted pyridines is described. This protocol has two steps: an aminocatalyzed addition of ketones to alkylidene isoxazol-5-ones, followed by an iron-mediated decarboxylative cyclization event. Mechanistic insights for both steps are provided based on HRMS-ESI(+) studies.
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Disclosed herein is a photo-organocatalytic enantioselective α- and γ-alkylation of aldehydes and enals, respectively, with bromomalonates. The chemistry uses a commercially available aminocatalyst and occurs under illumination by a fluorescent light bulb in the absence of any external photoredox catalyst. Mechanistic investigations reveal the previously hidden ability of transiently generated enamines to directly reach an electronically excited state upon light absorption while successively triggering the formation of reactive radical species from the organic halides. At the same time, the ground state chiral enamines provide effective stereochemical induction for the enantioselective alkylation process.
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A metal-free, photochemical strategy for the direct alkylation of indoles was developed. The reaction, which occurs at ambient temperature, is driven by the photochemical activity of electron donor-acceptor (EDA) complexes, generated upon association of substituted 1H-indoles with electron-accepting benzyl and phenacyl bromides. Significant mechanistic insights are provided by the X-ray single-crystal analysis of an EDA complex relevant to the photoalkylation and the determination of the quantum yield (Φ) of the process.
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An arylation strategy allowing the conversion of alkyl 2-((diphenoxyphosphoryl)oxy)-2-arylacetates to α,α-diaryl esters is reported. This transformation can be promoted by TfOH when the starting organic phosphates do not carry para-alkoxy groups on their aryl rings, but it does not require any additives when such groups are present. These alkyl 2-((diphenoxyphosphoryl)oxy)-2-arylacetates can be readily accessed from the insertion of diphenyl phosphate into aryldiazoacetates.
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Considering the recent rapid advancement of synthetic technologies promoted by visible light in the last 15 years, the use of photocatalysts has been rightfully justified based on the fact that organic molecules generally do not absorb visible light. However, an increasing number of different classes of organic molecules is being identified as actually directly absorbing in this region of the electromagnetic spectrum. Among them, diazo compounds are possibly one of these classes whose chemistry has been more explored so far. Indeed, irradiation of these compounds with visible light has been introduced as a mild photolytic strategy generally leading to free carbene intermediates. This strategy not only allows for a more cost-economical approach revealing similar outcomes to some previously reported thermal, metal-catalyzed transformations; but it can also eventually lead to different reactivities. Herein, we will present the contributions of our laboratory and of other groups to this research area, along with some important elements of design behind the development of selected reaction profiles, aiming to provide the reader with an overall view of the current state of the art.
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An aza-Robinson annulation strategy is described using a NaOEt-catalyzed conjugate addition of cyclic imides onto vinyl ketones, followed by a TfOH-mediated intramolecular aldol condensation to afford densely functionalized fused bicyclic amides. The potential use of these amides in the synthesis of alkaloids is demonstrated by the sequential conversion of appropriate precursors to (±)-coniceine and quinolizidine in two additional steps, thus allowing their preparation in overall 40 and 44% yields, respectively.
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Rearranging its feathers: The transformation of simple linear amides into a diverse range of branched, functionalized products by conversion to iminium esters is followed by sequential treatment with nucleophiles and electrophiles (see scheme). The method takes advantage of a novel Claisen rearrangement and the use of aromatic substrates greatly facilitates the formation of the intermediate iminium ether.
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A new visible-light-promoted reaction between aryldiazoacetates and 1,3-diketones allows good yields and selectivities for C-C bond insertions, leading to the corresponding 1,4-dicarbonyl compounds. This transformation is straightforward and highly practical. It tolerates air and moisture and does not require the use of any metals. Mechanistic investigations support the involvement of a key cyclopropanol intermediate derived from an intramolecular rearrangement.
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Two new visible-light-mediated strategies are described starting from aryldiazoacetates. The first approach describes their reaction with azides to afford the corresponding imines, and then reaction with aryldiazoketones produces alkyl 2-carboxylate-2,3,3-trisubstituted ß-lactams. The second approach describes the reaction with sulfoxides to afford the corresponding sulfoxonium ylides, followed by reaction with aryldiazoketones to produce 5-alkoxy-2,2,4-trisubstituted furan-3(2H)-ones. These protocols take advantage of the photolysis of aryldiazoacetates and the photochemically promoted Wolff rearrangement of aryldiazoketones.
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A simple, inexpensive, step economic, and highly modular synthetic strategy to access izidine alkaloids is described. The key step is a TfOH-promoted intramolecular aldol condensation between enol and cyclic imide moieties. This cyclization strategy can be employed within an aza-Robinson annulation framework and represents a general tool to build fused bicyclic amines. To illustrate the power of this method, we describe the preparation of (±)-coniceine, (±)-quinolizidine, (±)-tashiromine, (±)-epilupinine, and the core of (±)-valmerins.
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Alpiniamide A is a linear polyketide produced by Streptomyces endophytic bacteria. Despite its relatively simple chemical structure suggestive of a linear assembly line biosynthetic construction involving a hybrid polyketide synthase-nonribosomal peptide synthetase enzymatic protein machine, we report an unexpected nonlinear synthesis of this bacterial natural product. Using a combination of genomics, heterologous expression, mutagenesis, isotope-labeling, and chain terminator experiments, we propose that alpiniamide A is assembled in two halves and then ligated into the mature molecule. We show that each polyketide half is constructed using orthogonal biosynthetic strategies, employing either cis- or trans-acyl transferase mechanisms, thus prompting an alternative proposal for the operation of this PKS-NRPS.
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Proteínas de Bactérias/metabolismo , Peptídeo Sintases/metabolismo , Policetídeos/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Domínio Catalítico , Genômica , Família Multigênica , Peptídeo Sintases/química , Peptídeo Sintases/genética , Domínios Proteicos , Streptomyces/genética , Streptomyces/metabolismoRESUMO
A thermal protocol is reported for the formal insertion of nitric acid into aryldiazoacetates using Fe(NO3)3·9H2O. This strategy is mild and high yielding and allows the preparation of a large variety of members of an unprecedented family of organic nitrates. The nitrate group can be also readily transformed into other functional groups and heterocyclic moieties and can possibly allow new biological explorations of untapped potential associated with their NO-releasing ability.
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Aryldiazoacetates can undergo photolysis under blue light irradiation (460-490 nm) at room temperature and under air in the presence of numerous trapping agents, such as styrene, carboxylic acids, amines, alkanes and arenes, thus providing a straighforward and general platform for their mild functionalization.