pinecone/core-2020-05-10-deduplication huggingface dataset:
Synthesis of 2,6-bis-(oxazolyl)pyridine ligands for luminescent Ln(III) complexes

Submitted to the European Journal of Organic ChemistryNew bis-(oxazolyl)pyridine ligands for Ln(III) ions were prepared using a expeditious methodology from threonine and dipicolinic acid chloride.  The synthetic strategy includes a dehydration step to give a bis-dehydroaminobutyric acid derivative followed by bromination and cyclization with DBU. Photophysical studies of Eu(III) and Tb(III) complexes of these ligands showed that the 2,6-bis-(oxazolyl)pyridine moiety acts as an effective sensitizer for lanthanide luminescence and indicate the formation of 3:1 complexes [Ln-(bis-(oxazole)pyridine)3]3+.Fundação para a Ciência e Tecnologia (FCT), QREN, FEDER/E
Enantioselective Synthesis of Succinimides by Michael Addition of 1,3-Dicarbonyl Compounds to Maleimides Catalyzed by a Chiral Bis(2-aminobenzimidazole) Organocatalyst

A wide variety of chiral succinimides have been prepared in high yields and enantioselectivities by asymmetric conjugate addition of 1,3-dicarbonyl compounds to maleimides under very mild reaction conditions using a bifunctional benzimidazole-derived organocatalyst. Computational and NMR studies support the hydrogen-bonding activation role of the catalyst and the origin of the stereoselectivity of the process.Financial support from the Ministerio de Educación y Ciencia (MEC) (project numbers CTQ2007-62771/BQU, CTQ2010-20387), from Consolider INGENIO 2010 (grant number CSD2007-00006), from the Generalitat Valenciana (PROMETEO/2009/038), from Fondos Europeos para el Desarrollo Regional (FEDER), from the University of Alicante, and from the European Union (EU) (ORCA Action CM0905) is acknowledged
Synthesis of fluorescent alanines by a rhodium catalysed conjugate addition of arylboronic acids to dehydroalanine derivatives

Several arylalanine derivatives containing fluorescent groups were prepared in good yields using a rhodium catalysed conjugate addition of arylboronic acids to N,N-diprotected and N-monoprotected dehydroalanines. The best conditions for these reactions require the use of an excess of aryl boronic acid (4 equiv.), [Rh(COD)2]BF4 as catalyst and CsF as base in dioxane:H2O (10:1) at 110 ºC. These conditions were also applied to several dipeptides with dehydroalanine residues. The photophysical properties of some of the arylalanines were studied in three solvents of different polarity. Due to the absence of the, double bond, the absorption and fluorescence emission of the new compounds are dominated by the photophysical properties of the polycyclic aromatic fluorophores (naphthalene, phenanthrene and pyrene). Considering the relatively high fluorescence quantum yield of these compounds, some of them may be useful as fluorescent markers for peptides and proteins.Thanks are due to the Foundation for Science and Technology (FCT, Portugal), Quadro de Referencia Estrategico Nacional (QREN), and Fundo Europeu de Desenvolvimento Regional/Uniao Europeia (FEDER/EU) for financial support through the research centers, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)] and CFUM [PEst-C/FIS/UI0607/2011 (F-COMP-01-0124-FEDER-022711)], and project PTDC/QUI/81238/2006 (cofinanced by Fundo Europeu de Desenvolvimento Regional/Programa Operacional Fatores de Competitividade (FEDER/COMPETE), ref. FCOMP-01-0124-FEDER-007467). G. P. acknowledges her PhD grant from Fundacao para a Ciencia e a Tecnologia (FCT), Programa Operacional Potencial Humano/Quadro de Referencia Estrategico Nacional (POPH-QREN), Fundo Social Europeu (FSE) (SFRH/BD/38766/2007)
Synthesis and Biological Evaluation of a-Tubulin-Binding Pironetin Analogues with Enhanced Lipophilicity

The preparation of four new lipophilic analogues of the natural pyrone pironetin is described. The nine-carbon side chain of the latter has been replaced in one analogue by a 4-phenylbutyl chain and in the other three analogues by long aliphatic chains of thirteen and sixteen carbons, all of them bearing two stereogenic centers.
Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that all four are cytotoxic towards two either sensitive or resistant tumoral cell lines with similar IC50 values in each case, thus indicating that, like the parent natural compound, they also display a covalent mechanism of action. However, one of them operates in all likelihood through a mechanism very similar to pironetin whereas the other three seem to be cytotoxic via a different mechanism
Synthesis, Properties and Redox Behavior of Ene-Diyne Scaffolds Bearing 1- and 2-Azulenyl Groups at the Periphery

Ene-diyne systems possessing 1- and 2-azulenyl groups at the periphery were prepared by palladium-catalyzed cross-coupling reaction of 1- and 2-ethynylazulenes with 9-di-bromomethylene-9H-fluorene and 9,10-bis(dibromomethylene)-9,10-dihydroanthracene or 2-iodoazulene with 9,10-bis(diethynylmethylene)-9,10-dihydroanthracene under Sonogashira-Hagihara conditions. The redox behavior of the ene-diyne compounds was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Moreover, a significant color change of the ene-diyne derivatives was observed with visible spectroscopy under electrochemical reduction conditions
Synthetic Studies directed towards Asmarines

The present thesis is focused on the design of synthetic routes towards asmarine analogues. Asmarines are marine natural products isolated from the sponges Raspalia sp. The asmarine molecule contains a seven-membered ring fused with a purine core. This tetrahydrodiazepinopurine moiety has previously been constructed for example by ringclosing metathesis (RCM). We were focused on developing this RCM reaction pathway further, in order to introduce a chiral centre to the 7-membered ring. The attempts to employ chiral allylic amines in the strategy were not successful. However, we managed to achieve the synthesis of the seven-membered ring by a novel synthetic approach employing Ru-catalysed double bond migration and Cu-catalysed C-N coupling. Thus, a new method for double bond migration of N-allyl purines was successfully developed, involving the substrate 7-allyl-6-iodo-7H-purine and the catalyst RuClH(CO)(PPh3)3. Furthermore, the possibilities of C-N bond formation between tert-butyl allylcarbamate and 7-alkylated 6-halopurines were investigated. Suitable conditions for the coupling were determined using the Goldberg reaction and 6-iodo-7-(prop-1-en-1-yl)-7Hpurine was successfully coupled with tert-butyl allylcarbamate, giving tert-butyl allyl(7-(prop-1-en-1-yl)-7H-purin-6-yl)carbamate. Finally, the RCM with this intermediate led to the previously known 7,8,9,10-tetrahydro-[1,4]diazepino[1,2,3-gh]purine. In addition, attention is paid to the synthesis and rearrangement of N-allyl to Npropenyl purines. There are very few convenient routes to N-alkenylpurines in general. Therefore, we have carried out a study on the isomerisation of 9-allyl- and 7-allylpurines. Various N-allyl purines were prepared, and base- or transition metal complex promoted isomerisations were explored. Subsequently, this study was extended for substrates bearing additional substitution on the allyl chain. Scope and limitation of the double bond migration methodologies and E/Z selectivity is discussed
Approaches to the Synthesis of a Water-soluble Carboxy Nitroxide

The robust and diversely useful isoindoline nitroxide, 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (1; CTMIO), has previously been synthesised in low-to-moderate yields from phthalic anhydride (3). Recent interest in its biological potential as a potent antioxidant and in other areas has seen an increased demand for its production. Herein, three new synthetic routes to CTMIO are presented and their efficiencies assessed. Two routes, via the nitrile 9 and the formyl compound 11, derive from 5-bromo-1,1,3,3-tetramethylisoindoline (6). The third approach starts from the readily accessible starting material, 4-methylphthalic anhydride (12), and proceeds by a methylarene oxidation with potassium permanganate. The three new approaches yield CTMIO in comparable overall yields (16–18 %); however, the synthetic efficiency is most improved when employing the nitrile intermediate 9
(β-D-ribofuranosyl)formamidine in the design and synthesis of 2-(β-D-ribofuranosyl)pyrimidines, including RF-containing derivatives

A wide range of novel 2-(β-D-ribofuranosyl)pyrimidines, including RF-containing derivatives, have been synthesized by the reaction of (β-D-ribofuranosyl)formamidine with various dielectrophilic substrates such as 3-alkoxy- and 3-chloro-1-(polyfluoroalkyl)propen-1-ones, 3-nitro- and 3-(phenylethynyl)chromones and heteroaryl acetylenic ketones. Polyfluoroalkyl-containing 2-(β-D-ribofuranosyl)pyrimidine derivatives have been synthesized by the reaction of (β-D-ribofuranosyl)formamidine with dielectrophilic substrates such as 3-alkoxy- and 3-chloro-1-(polyfluoroalkyl) propen-1-ones, 3-nitro- and 3-(phenylethynyl)chromones and heteroaryl acetylenic ketones. Copyright © 2013 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim
Molecular tweezers with freely rotating linker and porphyrin moieties

Molecular tweezers were synthesised by using a microwave accelerated alkene plus cyclobutane epoxide reaction between norbornyl appended porphyrin moieties and a diepoxide functionalised phenyl diimide spacer. The tweezers contain several rotational degrees of freedom; about the porphyrin with respect to the norbornyl linker, and between the two norbornyl backbone sections. The ability of Zn(super)II metallated tweezer 1 to complex 1,4-diazabicyclo[2.2.2]octane (DABCO) was studied by UV/Vis and ¹H NMR spectroscopy and multivariate global spectral analysis. The system was found to form a strong 1:1 intramolecular complex (1:DABCO) with an association constant of K₁₁ = 8.1 × 10⁷ M⁻¹, transforming to a 1:2 open complex [1:(DABCO)₂] with K₁₂ = 2.7 × 10⁹ M⁻² at high concentrations of DABCO.Rhys B. Murphy, Duc-Truc Pham, Stephen F. Lincoln, and Martin R. Johnsto
A General Procedure for the Regioselective Synthesis of Aryl Thioethers and Aryl Selenides Through C–H Activation of Arenes

A general procedure for the synthesis of aryl thioethers and aryl selenides in one-pot through sequential iridium-catalyzed C–H borylation and copper-promoted C–S and C–Se bond formation is described. Functional groups including chloro, nitro, fluoro, trifluoromethyl, and nitrogen-containing heterocycles were all tolerated under the reaction conditions. Importantly, not only aryl thiols and selenides but also their alkyl analogs were suitable coupling partners, and the products were obtained in good yields with high meta regioselectivity
Enantioselective Synthesis of Succinimides by Michael Addition of Aldehydes to Maleimides Organocatalyzed by Chiral Primary Amine-Guanidines

The monoguanylation of (1S,2S)- and (1R,2R)-cyclohexane-1,2-diamine affords chiral primary amine-guanidines that are used as chiral organocatalysts in the enantioselective Michael addition of aldehydes, particularly α,α-disubstituted aldehydes, to maleimides. The reaction is carried out in the presence of imidazole, as an additive, in aqueous N,N-dimethylformamide, as the solvent, and affords the corresponding enantioenriched succinimides in high or quantitative yields with enantioselectivities up to 96 % ee. Theoretical calculations (DFT and M06–2X) suggest a different hydrogen-bonding coordination pattern between the maleimide (C=O) and the catalyst (NH groups) is responsible for the enantioinduction switch that is observed when the reaction is carried out using primary amine-guanidines versus primary amine-thioureas as the organocatalysts.The authors thank the Spanish Ministerio de Economía y Competitividad (MEC) (projects CTQ2010-20387, CTQ2010-21263-C02, and Consolider Ingenio 2010, CSD2007-00006), the Fondos Europeos para el Desarrollo Regional (FEDER), the COST Action CM0905 “Organocatalysis”, the Generalitat Valenciana (Prometeo/2009/039), the Basque Government (GV grant IT-291-07), the University of Alicante, and the University of the Basque Country for the financial support
Direct amidation of amino acid derivatives catalyzed by arylboronic acids : applications in dipeptide synthesis.

The direct amidation of amino acid derivatives catalyzed by arylboronic acids has been examined. The reaction was generally slow relative to simple amine-carboxylic acid combinations though proceeded at 65–68 °C generally avoiding racemization. 3,4,5-Trifluorophenylboronic and o-nitrophenylboronic acids were found to be the best catalysts, though for slower dipeptide formations, high catalyst loadings were required and an interesting synergistic catalytic effect between two arylboronic acids was discovered
Recent Advances in the Catalytic Enantioselective Reformatsky Reaction

This paper reviews the present state of the catalytic enantioselective Reformatsky reaction. Advancements in asymmetric versions of this reaction have recently led to a considerable extension of its scope and applicability, principally due to the use of highly active chiral ligands and very specific reaction conditions.M. A. F. I. is grateful for financial support from the Ministerio de Economía y Competitividad (MINECO) (CTQ 2012-35790) and the Consejería de Educación de la Comunidad de Madrid (programme AVANCAT, S2009/PPQ-1634). B. M. thanks the European Commission for a Marie Curie Integration Grant (FP7-PEOPLE-2012-CIG). I. M. P. and D. A. A. are grateful for financial support from the Spanish Ministerio de Ciencia e Innovación (MICINN) (project numbers CTQ2011-24165 and CTQ2010-20387, respectively) and from the University of Alicante
Copper-Free Oxime–Palladacycle-Catalyzed Sonogashira Alkynylation of Deactivated Aryl Bromides and Chlorides in Water under Microwave Irradiation

Palladium-catalyzed Heck alkynylation cross-coupling reactions between terminal alkynes and deactivated aryl chlorides and aryl bromides can be performed in the absence of copper cocatalyst with water as solvent at 130 °C under microwave irradiation. An oxime-derived chloro-bridged palladacycle is an efficient precatalyst for this transformation with 2-dicyclohexylphosphanyl-2′,4′,6′-triisopropylbiphenyl (XPhos) as ancillary ligand, pyrrolidine as base, and SBDS as surfactant. All of the reactions can be performed under air and with reagent-grade chemicals under low loading conditions (0.1–1 mol-% Pd).Financial support from the Ministerio de Economía y Competitividad (MINECO) (project CTQ2010-20387), Consolider INGENIO (project 2010 CSD2007-00006), Fondos Europeos para el Desarrollo Regional (FEDER), the Generalitat Valenciana (project PROMETEO/2009/038), and the University of Alicante is acknowledged
Organophosphorus-Selenium Heteroatom Derivatives from Selenation of Primary/Secondary Amines and Haloalkanes/Dihaloalkanes

Reaction of 2,4-bis(phenyl)-1,3-diselenadiphosphetane-2,4-diselenide (Woollins' reagent) with four equivalents of primary/secondary amines led to a series of ammonium phenylphosphonamido-diselenoates or phenylphosphonamido-diselenoic diamides 1a-n, the latter further reacted in situ with either two equivalents of haloalkanes or an equimolar amount of dihaloalkane, resulting in formation of the corresponding Se-alkylphenyl-Se-alkylphenyl-phosphonamidodiselenoates 2a-n and alkane bis(N-alkyl-P-phenylphosphonamido-diselenoate) derivatives 3a-n in good to excellent yields. All new compounds have been characterized spectroscopically including multinuclear NMR (H-1, C-13, P-31 and Se-77), IR and mass spectroscopy. Two representative X-ray structures are also described.PostprintPeer reviewe
Synthesis and Properties of Azulene-Substituted Donor-Acceptor Chromophores Connected by Arylamine Cores

1-Ethynylazulenes connected by several arylamine cores reacted with tetracyanoethylene (TCNE) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) in a formal [2+2] cycloaddition-cycloreversion reaction to afford the corresponding tetracyanobutadiene (TCBD) and dicyanoquinodimethane (DCNQ) chromophores, respectively, in excellent yields. The intramolecular charge-transfer (ICT) characters between the donor (azulene and arylamine cores) and acceptor (TCBD and DCNQ units) moieties were investigated by UV/Vis spectroscopy and theoretical calculations. The redox behavior of the new TCBD and DCNQ derivatives was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed their multistep electrochemical reduction properties. Moreover, significant color changes were observed by visible spectroscopy under the electrochemical reduction conditions
1,2-Functionalized Imidazoles as Palladium Ligands: An Efficient and Robust Catalytic System for the Fluorine-Free Hiyama Reaction

A variety of hydroxy- and amino-functionalized imidazoles were prepared from 1-methyl- and 1-(diethoxymethyl)imidazole by means of isoprene-mediated lithiation followed by reaction with an electrophile. These compounds in combination with palladium acetate were screened as catalyst systems for the Hiyama reaction under fluorine-free conditions using microwave irradiation. The systematic study of the catalytic system showed 1-methyl-2-aminoalkylimidazole derivative L1 to be the best ligand, which was employed under solvent-free conditions with a 1:2 Pd/ligand ratio and TBAB (20 mol-%) as additive. The study has revealed an interaction between the Pd/ligand ratio and the amount of TBAB. The established catalytic system presented a certain degree of robustness, and it has been successfully employed in the coupling of a range of aryl bromides and chlorides with different aryl siloxanes. Furthermore, both reagents were employed in an equimolecular amount, without an excess of organosilane.Financial support from the Spanish Ministerio de Ciencia e Innovación (MICINN) (project numbers CTQ2007-65218, CTQ2011-24165), from Consolider Ingenio 2010 (CSD2007-00006), from the Generalitat Valenciana (PROMETEO/2009/039), from the Fondos Europeos para el Desarrollo Regional (FEDER) and from the Universidad de Alicante is acknowledged
Cyclocondensation of Hydroxylamine with 1,3-Bis(het)arylmonothio 1,3-Diketones and 1,3-Bis(het)aryl-3-(methylthio)-2-prop­enones: Synthesis of 3,5-Bis(het)arylisoxazoles with Complementary Regioselectivity

Efficient routes for the regioselective synthesis of 3,5-bis(het)arylisoxazoles with complementary regioselectivity have been developed. The methods involve the cyclocondensation of hydroxylamine hydrochloride with either 1,3-bis(het)aryl-monothio-substituted 1,3-diketones 1 or with 3-methylthio-1,3-bis(het)aryl-2-propenones 2 under various reaction conditions. In the first protocol, diketones 1 were treated with hydroxylamine hydrochloride in the presence of sodium acetate/acetic acid (pH 2.2) in refluxing ethanol/benzene to give 3,5-bis(het)arylisoxazoles 5, in which the het(aryl) moiety attached to thiocarbonyl group of the monothio-substituted 1,3-diketones is installed at the 3-position. On the other hand, the reaction of hydroxylamine hydrochloride with 3-(methylthio)-1,3-bis(het)aryl-2-propenones 2 in the presence of barium hydroxide in refluxing ethanol gave 3,5-bis(het)arylisoxazoles 6 with complementary regioselectivity in high yields. A probable mechanism for the formation of regioisomeric isoxazoles 5 and 6 from precursors 1 and 2 has been suggested
Design and Synthesis of Pironetin Analogue/Combretastatin A-4 Hybrids and Evaluation of Their Cytotoxic Activity

We describe the preparation of a series of hybrid molecules containing a combretastatin A-4 moiety and a pironetin analogue fragment linked by an ester spacer of variable length. The cytotoxic activities of these compounds have been measured and the relationship between the structure and cytotoxicity is discussed. Some of the tested compounds showed cytotoxicity values of the same order of magnitude as those of the parental molecules, combretastatin A-4 and pironetin, and were less toxic than the latter for normal cells
Mechanistic Insight into the Lability of the Benzyloxycarbonyl (Z) Group inN-Protected Peptides under Mild Basic Conditions

The unexpected lability of Z protecting group under mild basic conditions at room temperature is explained by a mechanism based on anchimeric assistance. It is found that the vicinal amide group stabilizes the tetrahedral intermediate formed after the nucleophilic addition of hydroxide to the carbonyl of the Z group. This effect 	operates in N-protected tripeptides and tetrapeptides but Z-protected dipeptides are stable under the same conditions due to the blockage of the vicinal amide NH by intramolecular H-bonding with terminal carboxylate moiety
Efficient Synthesis and Versatile Reactivity of Porphyrinyl Grignard Reagents

Iodine–magnesium exchange between iodoporphyrins and iPrMgCl·LiCl proceeded successfully without decomposition of the porphyrin core. The resulting porphyrinyl Grignard reagents are nucleophilic enough to react with various carbonyl compounds, such as aldehydes, ketones, and amides. Furthermore, the porphyrinyl Grignard reagents underwent transmetalation to afford porphyrinyl copper and zinc species of mild and unique reactivity. These could be engaged in 1, 4-addition and Negishi coupling, respectively
Rhodium-NHC hybrid silica materials as recyclable catalysts for [2+2+2] cycloaddition reactions of alkynes

Bis-silylated dihydroimidazolium salt 1 and monosilylated imidazolium salt 2 are transformed to (NHC)RhCl(COD) complexes 3 and 4, allowing the preparation of hybrid silica materials either by sol-gel or grafting processes. Full characterization of the materials by means of solid state NMR, N₂-sorption measurements, thermogravimetric analysis (TGA) and elemental analysis was followed by evaluation of catalytic activity in the [2+2+2] cycloaddition of alkynes. Excellent yields of the cycloadducts are obtained for up to six consecutive cycles with the grafted material, using simple filtration to recover the catalyst. Both conventional and microwave heating prove effective for the process described
Assembly of a 1H-Pyrrol-2(5H)-one Core through a Cascade Ugi Reaction/5-endo-dig Carbocyclization/Retro-Claisen Fragmentation Process

A cascade transformation involving the Ugi reaction followed by 5-endo-dig carbocyclization and retro-Claisen fragmentation providing access to a 1H-pyrrol-2(5H)-one core is described. The operating protocol is very similar to the typical Ugi reaction settings, while the overall outcome results from the application of a 3-substituted propiolic acid and a phenylglyoxal as acid and aldehyde components, respectively. The utility of process is demonstrated through the synthesis of a small library of 5-oxo-2,5-dihydro-1H-pyrrole-2-carboxamides.status: publishe
Multigram Four-Step Synthesis of 1,4,7-Triazacyclononanes with 2Ra/Rb N-Functionalization Pattern by Starting from Diethylenetriamine

International audiencePolyazamacrocycles and their derivatives are appreciated for the strength of their corresponding metal complexes. 1,4,7-Triazacyclononane (TACN) derivatives have been employed in an ever increasing number of applications. To this day, all synthetic routes to TACN derivatives that have identical or differing substituents require the initial preparation of unprotected TACN. Herein, we report the four-step synthesis of TACN derivatives that have a 2Ra/Rb N-functionalization pattern by starting from diethylenetriamine and employing an organic template strategy