pinecone/core-2020-05-10-deduplication huggingface dataset:
Deep Eutectic Solvents: The Organic Reaction Medium of the Century

This microreview summarizes the use of deep eutectic solvents (DESs) and related melts in organic synthesis. Solvents of this type combine the great advantages of other proposed environmentally benign alternative solvents, such as low toxicity, high availability, low inflammability, high recyclability, low volatility, and low price, avoiding many disadvantages of the more modern media. The fact that many of the components of these mixtures come directly from nature assures their biodegradability and renewability. The classification and distribution of the reactions into different sections in this microreview, as well as the emphasis paid to their scope, easily allow a general reader to understand the actual state of the art and the great opportunities opened, not only for academic purposes but also for industry.This work was supported by the University of Alicante, Spain (VIGROB-173 and UAUSTI13-09)
The Synthesis of Quinolone Natural Products from Pseudonocardia sp.

The synthesis of four quinolone natural products from the actinomycete Pseudonocardia sp. is reported. The key step involved a sp2–sp3 Suzuki-Miyaura reaction between a common boronic ester lateral chain and various functionalised quinolone cores. The quinolones slowed growth of E. coli and S. aureus by inducing extended lag phases.The research leading to these results has received funding from the European Reserach Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC grant agreement no [279337/DOS]. Research in the DRS lab is also supported by the Engineering and Physical Sciences Research Council, Biotechnology and BiologicalSciences Research Council, Medical Research Council, Cancer Research UK, and the Wellcome Trust. Work in the MW lab is supported by the BBSRC and MRC.  JTH was supported by Trinity College Cambridge. Data accessibility: all data supporting this study are provided as Supplementary Information accompanying this paper.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/ejoc.20150140
The generation of a library of bromodomain-containing protein modulators expedited by continuous flow synthesis.

A continuous flow process delivering key building blocks for a series of BCP modulator libraries is reported. A dynamically mixed flow reactor emerged as a pivotal technology in both synthesis and isolation phases enabling the processing of slurries and suspensions while maintaining high productivity and reliability. Accordingly, the synthesis of common intermediates in flow were employed to further build a pyridazone-based library (36 compounds) aimed at improving lead compound potency and selectivity while further enabling structure-activity relationship studies of a new BCP modulator family
Bis-Sulfone- and Bis-Sulfoxide-Spirobifluorenes: Polar Acceptor Hosts with Tunable Solubilities for Blue-Phosphorescent Light-Emitting Devices

Bis-sulfone- and bis-sulfoxide-spirobifluorenes are a promising class of high-triplet-energy electron-acceptor hosts for blue phosphorescent light-emitting devices. The molecular design and synthetic route are simple and facilitate tailoring of the solubilities of the host materials without lowering the high-energy triplet state. The syntheses and characterization (including single-crystal structures) of four electron-accepting hosts are reported; the trend in their reduction potentials is consistent with the electron-withdrawing nature of the sulfone or sulfoxide substituents. Emission maxima of 421–432 nm overlap with the MLCT absorption of the sky-blue emitter bis(4,6-difluorophenyl-pyridinato)(picolinato)iridium(III) (FIrpic), allowing effective energy transfer from the acceptor hosts to FIrpic. Theoretical calculations show that the introduction of sulfone groups leads to better electron acceptors compared to analogous phosphine oxide functionalized hosts and, at the same time, preserves the energy of the lowest-lying triplet above that of the FIrpic emitter. The new hosts have been tested in phosphorescent light-emitting electrochemical cells (LECs). Large effects of the various solubilizing moieties on the device performance are observed and discussed
Hydrogen-Bonding Network Anchors the Cyclic Form of Sugar\ud
Arylhydrazones\ud

The “classical” challenge, raised by Emil Fischer as to\ud
why one monosaccharide arylhydrazone adopts a cyclic structure but another an acyclic structure, is answered here. The present comprehensive analysis of hexose and hexosamine arylhydrazones, based on 2D NMR spectroscopy and theoretical modeling, has established that the chain of hydrogen bonds needed for conformational selection can only be completed for D-glucosamine derivatives. Thus, D -glucosamine 4-nitrophenyl-hydrazone exclusively adopts its cyclic form, but any configurational changes imply the formation of acyclic structures. In conclusion, three criteria dominate structure selection, namely 1) an amino function at the C-2 position, 2) the “all-equatorial”\ud
substitution mode of the pyranoid ring, and 3) an electron-\ud
withdrawing group on the arylhydrazone are all needed to get\ud
the cyclic form only.\u
Quinidine-Catalysed Enantioselective Synthesis of 6- and 4-Trifluoromethyl-Substituted Dihydropyrans

The authors thank the Royal Society for a University Research Fellowship (ADS) and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013), ERC Grant Agreement No. 279850 (KK), the authors also thank the EPSRC UK National Mass Spectrometry Facility at Swansea University.The cinchona alkaloid-catalysed enantioselective formal [4+2] cycloaddition of ethyl 2,3-butadienoate with a range of 1,1,1-trifluoro- and 4,4,4-trifluorobutenones is investigated for the preparation of stereodefined 6- and 4-trifluoromethyl-substituted dihydropyrans. Quinidine proved to be the optimal catalyst, generating the desired products in up to 98 % ee and 81 % yield. Stereo- and chemoselective derivatization of the dihydropyrans through hydrogenation is explored.PostprintPeer reviewe
ortho-Lithiation Reactions of O-(3,n-Dihalophenyl) N,N-Diethylcarbamates: Synthesis of Dihalosalicylamides and 2,3,n-Trihalophenol Derivatives

New dihalosalicylamides and trihalophenol derivatives have been synthesized from easily available O-(3,n-dihalophenyl) N,N-diethylcarbamates by using a directed ortho-metalation (DoM) strategy. The o-lithiation reactions with sBuLi take place regioselectively at the doubly activated C-2 position, which demonstrates the ability of O-carbamates as directed metalating groups. In addition, highly functionalized arylnitriles were accessed from organolithium intermediates by using a tandem transnitrilation/SNAr reaction sequence.Junta de Castilla y León (Consejería de\ud
Educación) and FEDER (BU237U13 and BU076U16) as well as\ud
the Ministerio de Economía y Competitividad (MINECO) and\ud
FEDER (CTQ2013-48937-C2-1-P
Metal–Organic Framework Based on Copper and Carboxylate-Imidazole as Robust and Effective Catalyst in the Oxidative Amidation of Carboxylic Acids and Formamides

A metal–organic framework (MOF) based on copper and 1,3-bis(carboxymethyl)imidazole (bcmim) was prepared on a gram scale by using a precipitation method at room temperature. The Cu(bcmim)2 MOF was shown to be an efficient catalyst for the preparation of amides through an oxidative coupling between carboxylic acids and formamides in the presence of an oxidant, such as tert-butyl hydroperoxide (TBHP). The method for the preparation of the amides is robust regardless of the carboxylic acid and gives good conversions with good selectivity. The heterogeneous catalyst was recovered unaltered after the reaction, was easily separated from the reaction mixture, and subsequently reactivated by suitable treatment. Moreover, the coupling reaction was scaled up to a gram scale, which allowed for the preparation of valuable products, such as fatty acid amides (i.e., 1-palmitoylpiperidine).The Spanish Ministerio de Economía y Competitividad (CTQ2015-66624-P) and the University of Alicante
2-[(1E,3E)-4-Arylbuta-1,3-dien-1-yl]-4H-chromen-4-ones as dienes in Diels-Alder reactions - experimental and computational studies

The synthesis and reactivity of 2-[(1E,3E)-4-arylbuta-1,3-dien-1-yl]-4H-chromen-4-ones as dienes in Diels–Alder (DA) reactions with several electron-poor and electron-rich dienophiles under microwave irradiation was studied. The optimized reaction conditions were achieved with N-methylmaleimide as the dienophile and Sc(OTf )3 (OTf = triflate) as a Lewis acid under microwave-assisted and solvent-free conditions. The Lewis
acid improved the reaction yields as it prevented the adducts obtained from undergoing a second DA reaction; thus, the formation of a bisadduct was avoided. The α, :γ,δ-diene of the starting chromones was the most reactive, and the computational results confirmed the experimental findings. Theoretical calculations also provided a rationale for the unexpected lack of reactivity shown by some dienophiles. The adducts prepared were dehydrogenated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ); however, the aza adducts were sensitive to the highly energetic reaction conditions necessary for the aromatization.Thanks are due to University of Aveiro and FCT/Ministério da Educação e Ciência (MEC) for the financial support of the QOPNA research unit (FCT UID/QUI/00062/2013) and CIQ-UP (Pest-C/QUI/UI0081/2013) through national funds and, where applicable, cofinanced by the FEDER, within the PT2020 Partnership
Agreement, and to the Portuguese NMR Network, as well as to the Instituto Politécnico de Bragança. H. M. T. A. and C. F. R. A. C. L. are grateful to FCT for their PhD (SFRH/BD/86277/2012) and Postdoctoral (SFRH/BPD/77972/2011) grants, respectively.info:eu-repo/semantics/publishedVersio
Pyridone functionalization: regioselective deprotonation of 6-methylpyridin-2(1H)- and -4(1H)-one derivatives

This is the peer reviewed version of the following article: FERNANDEZ D.-R., B. ... et al, 2016. Pyridone functionalization: regioselective deprotonation of 6-methylpyridin-2(1H)- and -4(1H)-one derivatives. European Journal of Organic Chemistry, 2016(31), pp. 5238–5242., which has been published in final form at http://dx.doi.org/10.1002/ejoc.201601156. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Selective functionalization at the α-methyl group of 1-substituted pyridin-2(1H)- and 4(1H)-ones (2- and 4-pyridones) can be achieved by appropriate choice of base. n-Butyllithium was found to effect clean 6(2)-methyl deprotonation of 1-benzyl-2- and -4-pyridone derivatives, while potassium hexamethyldisilazide (KHMDS) was the preferred reagent for methyl deprotonation of the corresponding 1-methyl-2- and -4-pyridones. Deprotonation proceeds smoothly at –78 °C, and the resulting anions react readily with a wide range of electrophiles (aldehydes, ketones, alkylating reagents, and an azo compound) under precise temperature control to form usefully functionalized 2- and 4-pyridones and quinolizinones
A-Ring-Modified 2-Hydroxyethylidene Previtamin D3 Analogues: Synthesis and Biological Evaluation

To investigate the biological profile of the previtamin form of vitamin D, we have synthesized new analogues of 19-nor-1α,25-dihydroxyprevitamin D3 bearing a 2-hydroxyethylidene moiety at the A-ring. The target compounds were prepared by convergent synthesis employing the Sonogashira coupling between an A-ring enyne synthon and a CD-ring/side chain vinyl triflate. We have demonstrated the versatility of shikimic acid as starting material for the synthesis of the A-ring precursors. The binding affinity to Vitamin D Receptor (VDR) and Vitamin D Binding Protein (DBP), and MCF-7 cell antiproliferative activity have been evaluated
Facile Synthesis of Polycyclic Aromatic Hydrocarbons: Brønsted Acid Catalyzed Dehydrative Cycloaromatization of Carbonyl Compounds in 1,1,1,3,3,3-Hexafluoropropan-2-ol

The cycloaromatization of aromatic aldehydes and ketones was readily achieved by using a Brønsted acid catalyst in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP). In the presence of a catalytic amount of trifluoromethanesulfonic acid, biaryl-2-ylacetaldehydes and 2-benzylbenzaldehydes underwent sequential intramolecular cationic cyclization and dehydration to afford phenacenes and acenes, respectively. Furthermore, biaryl-2-ylacetaldehydes bearing a cyclopentene moiety at the α-position underwent unprecedented cycloaromatization including ring expansion to afford triphenylenes. HFIP effectively promoted the cyclizations by suppressing side reactions presumably as a result of stabilization of the cationic intermediates
Recyclable Chiral Bifunctional Thioureas Derived from [60]Fullerene and Their Use as Highly Efficient Organocatalysts for the Asymmetric Nitro-Michael Reaction

Producción CientíficaThree novel fullerothioureas derived from natural valine, phenylalanine, and tert-leucine have been prepared by Prato's reaction of [60]fullerene and the corresponding aldehydes. These hybrids have been used as organocatalysts in a typical stereoselective nitro-Michael addition reaction under homogeneous and neat conditions. The catalysts are easily recoverable by filtration, and are recyclable for at least five times. The addition products were obtained in excellent yields and stereoselectivities by using catalyst loadings of as low as 0.5 mol-%.2018-07-07Ministerio de Economía, Industria y Competitividad (Project CTQ2014-59870-P
An overview of 2-Styrylchromones: natural occurrence, synthesis, reactivity and biological properties

2-Styrylchromones are a small class of oxygen-containing heterocycles. Despite their sparse occurrence in nature, several synthetic approaches have been developed in order to synthesize a large variety of  derivatives, possessing different substituents in different positions of the main core. They are also versatile building blocks in the synthesis of new heterocyclic systems and important intermediates in the search for
bioactive compounds. It is our intention in this review to give a general overview on the natural occurrence, synthesis, reactivity and biological properties of 2-styrylchromones, which were published up until 2016.Thanks are due to the Instituto Politécnico de Bragança and
also to the University of Aveiro and the Formación en Centros
de Trabajo, Ministerio de Educación y Ciencia (FCT, MEC) for the
financial support of the QOPNA research unit (FCT UID/QUI/
00062/2013) through national funds and, where applicable, cofinanced
by the Fundo Europeu De Desenvolvimento Regional
(FEDER), within the PT2020 Partnership Agreement. Thanks are
also due to the Portuguese NMR Network.info:eu-repo/semantics/publishedVersio
Hybrid-Type Squaramide-Fused Amino Alcohol Organocatalysts for Enantioselective Nitro-Aldol Reaction of Nitromethane with Isatins

A series of new hybrid type squaramide-fused amino alcohol (SFAA) catalysts were synthesized and their catalytic efficiency in enantioselective nitro-aldol reaction of various isatins with nitromethane that afford the chiral 3-substituted 3-hydroxyoxindoles in excellent chemical yields (up to 99%) and high enantioselectivities (up to 95% ee) is described. The resulting chiral 3-hydroxyoxindoles could be used as synthetic precursors for the synthesis of several natural products with a broad spectrum of fascinating biological activities
Biodegradable Chitosan-Derived Thioureas as Recoverable Supported Organocatalysts – Application to the Stereoselective Aza-Henry Reaction

Producción CientíficaEight different biodegradable chitosan-supported bifunctional chiral thioureas have been prepared as a greener and more sustainable alternative to those supported on petrochemical-derived polymers. These organocatalysts promoted an enantioselective aza-Henry reaction, which afforded good product yields with moderate to high enantioselectivity. The activity and stereodirecting ability of these materials were dependent on the accessibility of the reactants to the active site and increased with the length of the tether that connected the thiourea to the biopolymer. The best performing catalyst was able to be recovered and recycled five times without a loss of activity.2018-10-10Ministerio de Economía, Industria y Competitividad (Project CTQ 2014-59870-P
Stannylated Vinylic Addition Polynorbornene: Probing a Reagent for Friendly Tin-Mediated Radical Processes

Producción CientíficaVinylic addition polynorbornenes (VA-PNB) with stannyl functional groups have been prepared and used in tin- mediated radical dehalogenation reactions. The aliphatic and robust scaffold of VA-PNB is well suited for a support in radical processes. VA-PNB-(CH2)nSnHBu2 can be used as a stoichiomet- ric reagent and VA-PNB-(CH2)nSnBu2Cl as a catalyst in the pres- ence of a hydride donor for the reduction of RBr. The mixture KF (aq.)/polymethylhydrosiloxane (PMHS) is the most convenient hydride source to generate VA-PNB-(CH2)nSnHBu2 in situ. Although quite popular in this context, boron hydrides, being a source of radicals themselves, are not adequate to correctly evaluate the performance of the anchored organotin group. VA- PNB-(CH2)4SnBu2Cl can be recycled and, even if it loses activity upon reuse, it is still useful after ten cycles. The stannylated VA- PNB can be separated from the products by simple filtration, and it leads to very low tin contamination (at least 250 times lower than that with use of conventional separation methods).MINECO-SGPI CTQ2013-48406-PMINECO-SGPI CTQ2016-80913-
A continuous-flow method for the desulfurization of substituted thioimidazoles applied to the synthesis of etomidate derivatives.

A simple yet robust flow set-up for the efficient desulfurization of a series of thioimidazoles is presented, which generates the corresponding imidazole derivatives in high yields. The strategic choice of peristaltic over piston pumps allowed reliable delivery of the heterogeneous stream of the thioimidazole substrate into a T-piece where it reacted with NaNO2 in the presence of acetic acid. This approach enabled the controlled and safe formation of the reactive nitrosonium species without uncontrolled exposure to hazardous nitrous oxide by-products as observed in related batch protocols. The value of the resulting imidazole products was further demonstrated by their conversion into various esters representing new derivatives of the known analgesic etomidate through an efficient one-pot Corey–Gilman–Ganem oxidation procedure
1,6-Conjugate Additions of Carbon Nucleophiles to 2-[(1E,3E)-4-Arylbuta-1,3-dien-1-yl]-4H-chromen-4-ones

KGaA, Weinheim The 1,6-conjugate addition of nitromethane to 2-[(1E,3E)-4-arylbuta-1,3-dien-1-yl]-4H-chromen-4-ones was accomplished and led mainly to the corresponding β-(nitromethyl)chromones. (E)-5′-(Nitromethyl)-3′-styryl-[1,1′-biphenyl] -2-ol and 3′-aryl-2′-nitro-5′-(nitromethyl)spiro[chromane-2,1′-cyclohexan]-4-one derivatives were also isolated as minor products from tandem processes, which result from the addition of a second molecule of nitromethane. The nucleophile scope was investigated with malononitrile, acetylacetone, ethyl cyanoacetate, and diethyl malonate, which gave the expected 1,6-addition products; in the last case, it was also possible to isolate a minor product formed through a 1,8-/1,6-addition sequence. Computational calculations provided a rationale for the experimental reactivity of carbon nucleophiles with 2-[(1E,3E)-4-arylbuta-1,3-dien-1-yl] -4H-chromen-4-ones. The further functionalization of some adducts allowed the preparation of new nitrogen-containing heterocyclic compounds, such as new styrylpyrrolidines and new pyrazole and bis(pyrazole) derivatives.Thanks are due to the University of Aveiro and Fundação para
a Ciência e a Tecnologia (FCT)/Ministerio de Educación y Ciencia
(MEC) for the financial support of the QOPNA research unit (FCT
UID/QUI/00062/2013) through national funds and, where applicable,
cofinanced by Fundo Europeu de Desenvolvimento Regional
(FEDER) within the PT2020 Partnership Agreement, and
to the Portuguese NMR Network as well as the Instituto Politécnico
de Bragança. H. M. T. A. is grateful to Fundação para a
Ciência e a Tecnologia (FCT) for his PhD grant (SFRH/BD/86277/
2012).info:eu-repo/semantics/publishedVersio
One-Pot Synthesis of 2-(Aryl/Alkyl)amino-3-cyanobenzobthiophenes and Their Hetero-Fused Analogues by Pd-Catalyzed Intramolecular Oxidative Câ��H Functionalization/Arylthiolation

We have developed a high-yielding synthesis for substituted 2-(aryl/alkyl)amino-3-cyanobenzobthiophenes and their hetero-fused analogues by using a palladium-catalyzed intramolecular oxidative Câ��H functionalization/arylthiolation reaction of in situ generated N-(alkyl/aryl)thioamides, prepared from readily available (hetero)arylacetonitriles and alkyl/aryl isothiocyanates. This protocol was then extended to the synthesis of amino-substituted benzothieno2,3-bquinolines by employing a triflic acid mediated intramolecular cyclocondensation of the prepared 2-arylamino-3-cyanobenzobthiophenes. Â© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei
Access to some C5-cyclised 2 pyrones and 2-pyridones via direct arylation; retention of chloride as a synthetic handle

The synthetic effort towards the functionalisation of C-H bonds on 2 pyrones and 2-pyridones has been funnelled by the preferential reactivity of the C-3 position. Herein, we report a direct arylation protocol for the intramolecular coupling of 2 pyrones and 2 pyridones, allowing access to a previously unavailable class of C-5 cyclised products with an unstudied biological profile. A C-Cl bond was retained at C-3 during the direct arylation process allowing further derivatisation at C-3, which we have demonstrated with a proof-of-principle Suzuki-Miyaura cross-coupling reaction
Stereodivergent syntheses of altro and manno stereoisomers of 2-acetamido-1,2-dideoxynojirimycin

A stereoselective synthesis of 2-acetamido-1,2-dideoxyaltronojirimycin (8) and its manno epimer 9 is described. The synthetic approach is based on key bicyclic carbamate 7, which is easily accessible with high enantiomeric purity on a multigram scale by Sharpless asym. epoxidn. of 1,4-pentadien-3-ol or 2,4-pentadien-1-ol. This procedure completes an efficient stereodivergent approach to five isomers of 2-acetamido-1,2-dideoxyiminosugars in high overall yields starting from the same key intermediate 7. The approach described in this paper is based on control of the stereoselectivity of the sulfite ring-opening reaction to give retention of configuration through anchimeric assistance from the endocyclic amine
Approaches to Pyranuronic β-Sugar Amino Acid Building Blocks of Peptidosaccharide Foldamers

Pyranuronic β-sugar amino acids (β-SAAs) are biocompatible and tuneable building blocks of foldamers and chimera-peptides. The scalable and economical total synthesis of two building blocks is described here. These C-4 epimers, Fmoc-GlcAPU(Me)-OH (7) and Fmoc-GalAPU(Me)-OH (8), which are suitable for solid phase peptide synthesis, were prepared via a common oxime intermediate 16. The new synthesis uses nine consecutive steps, starting from methyl α-d-glucopyranoside (6). The synthesis is fine-tuned, optimized, and ready for large-scale and cost-efficient production