- A short and efficient synthesis of the polyacetylene natural product deca-4,6,8-triyn-1-ol
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A practical and efficient four-step synthesis of the natural product deca-4,6,8-triyn-1-ol has been achieved beginning with (triisopropylsilyl)acetylene. This trialkyne has potential utility as a key intermediate for the total synthesis of the antitumor butenolide natural product vernoniyne.
- Machado, Vanessa Rocha,Biavatti, Maique Weber,Danheiser, Rick L.
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- Copper-Catalyzed Alkynylboration of Alkenes with Diboron Reagents and Bromoalkynes
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An efficient method for the synthesis of homopropargylboronates by copper-catalyzed alkynylboration of alkenes with diboron reagents and bromoalkynes has been developed. The alkynylboration reaction features high selectivity and efficiency, mild reaction conditions, wide substrate scope, and functional-group compatibility, and is a highly attractive complement to existing methods for the synthesis of homopropargylboronates. Both the boryl and alkynyl groups are good potential functional groups for the subsequent manipulations that provide access to a variety of important molecule structures.
- Gong, Tian-Jun,Yu, Shang-Hai,Li, Kuan,Su, Wei,Lu, Xi,Xiao, Bin,Fu, Yao
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- A Diversity Oriented Synthesis Approach to New 2,3- trans-Substituted l -Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors
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Discovery of chemical tools for the ionotropic glutamate receptors continues to be a challenging task. Herein we report a diversity-oriented approach to new 2,3-trans-l-proline analogs whereby we study how the spatial orientation of the distal carboxylate group influences the binding affinity and receptor class and subtype selectivity. In total, 10 new analogs were synthesized and 14 stereoisomers characterized in binding assays at native rat ionotropic glutamate receptors, and at cloned human homomeric kainic acid (KA) receptor subtypes GluK1-3. The study identified isoxazole analogs 3d,e, which displayed selectivity in binding at native N-methyl-d-aspartate (NMDA) receptors over native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and KA receptors, in the high nanomolar to low micromolar range. Furthermore, analogs 3i-A/B showed a preference in binding affinity for GluK3 over GluK1,2. Finally, analog 3j displayed high nanomolar affinity for native NMDA receptors as well as for homomeric GluK3 receptors.
- Bunch, Lennart,Kayser, Silke,Nielsen, Birgitte,Pickering, Darryl S.,Poulie, Christian B. M.,Staudt, Markus,Temperini, Piero
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- Palladium-Catalyzed Carboxy-Alkynylation of Propargylic Amines Using Carbonate Salts as Carbon Dioxide Source
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A palladium-catalyzed multicomponent reaction of propargylic amines, alkynyl bromides and cesium hydrogen carbonate to access oxazolidinones is reported. In contrast to previous reports, only a slight excess of cesium hydrogen carbonate is used as a surrogate of carbon dioxide. The reaction gives access to oxazolidinones bearing alkyl- and aryl polysubstituted enynes in good yield and very high E stereoselectivity.
- Greenwood, Phillip D. G.,Waser, Jerome
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- Organotellurium scaffolds for mass cytometry reagent development
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Mass cytometry (MC) is a powerful tool for studying heterogeneous cell populations. In previous work, our laboratory has developed an MC probe for hypoxia bearing a methyl telluride mass tag. The methyl telluride was unoptimized, displaying stability and
- Park, Hanuel,Edgar, Landon J.,Lumba, Matthew A.,Willis, Lisa M.,Nitz, Mark
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- Gold-catalyzed annulations of: N -aryl ynamides with benzisoxazoles to construct 6 H -indolo[2,3- b] quinoline cores
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This work reports new annulations of N-aryl ynamides with benzisoxazoles to form 6H-indolo[2,3-b]quinoline derivatives. The synthetic utility of this new method is manifested by its applicability to access naturally occurring alkaloids including norcryptotackeine, neocryptolepine and 11-methylneocryptol-epine. Our experimental data indicate that higherature conditions allow N-aryl nucleophiles to become conformationally flexible, rendering the attack at gold carbenes effective to generate reactive indoles that attack again the benzaldehyde to furnish the observed products.
- Tsai, Meng-Han,Wang, Cheng-Yu,Kulandai Raj, Antony Sekar,Liu, Rai-Shung
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- Isotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular Resolution
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Changes in the oxygenation state of microenvironments within solid tumors are associated with the development of aggressive cancer phenotypes. Factors that influence cellular hypoxia have been characterized; however, methods for measuring the dynamics of oxygenation at a cellular level in vivo have been elusive. We report a series of tellurium-containing isotopologous probes for cellular hypoxia compatible with mass cytometry (MC)—technology that allows for highly parametric interrogation of single cells based on atomic mass spectrometry. Sequential labeling with the isotopologous probes (SLIP) in pancreatic tumor xenograft models revealed changes in cellular oxygenation over time which correlated with the distance from vasculature, the proliferation of cell populations, and proximity to necrosis. SLIP allows for capture of spatial and temporal dynamics in vivo using enzyme activated probes.
- Edgar, Landon J.,Vellanki, Ravi N.,McKee, Trevor D.,Hedley, David,Wouters, Bradly G.,Nitz, Mark
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- Directed Nickel-Catalyzed pseudo-Anomeric C?H Alkynylation of Glycals as an Approach towards C-Glycoconjugate Synthesis
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The synthesis of complex C-glycoconjugates is presented here using a key directed nickel-catalyzed C?H alkynylation step. Thanks to a bidentate amidoquinoline-type directing group, the insertion of diverse alkynyl moieties onto the pseudo-anomeric position of glycal substrates was performed on ten examples in moderate to good yields. These platforms were used as starting substrates in a click reaction with complex azides to form original C-glycoconjugates. By this route, a C-glycosylated amino acid, a C-linked disaccharide and a C-glycosylated biotin derivative were synthesized. Preliminary conditions to remove the directing group are also proposed. (Figure presented.).
- de Robichon, Morgane,Branquet, David,Uziel, Jacques,Lubin-Germain, Nadège,Ferry, Angélique
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- A Copper-Catalyzed N-Alkynylation Route to 2-Substituted N-Alkynyl Pyrroles and Their Cyclization into Pyrrolo[2,1-c]oxazin-1-ones: A Formal Total Synthesis of Peramine
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Screening of a variety of ligands and reaction conditions for the copper-catalyzed cross-coupling of alkynyl bromides with pyrroles, reveals that the use of the phenanthroline ligand 4,7-dimethoxy-1,10-phenanthroline affords a range of ynpyrroles in good to moderate yields. Furthermore, the utility of these ynpyrroles is demonstrated in the preparation of a series of pyrrolo[2,1-c][1,4]oxazin-1-ones and a formal total synthesis of the pyrrole natural product peramine.
- Reinus, Brandon J.,Kerwin, Sean M.
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- Ethynylogation approach in pharmacophore design: from alkynyl-to butadiynyl-carbinols vs antitumoral cytotoxicity
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Ethynylogation of a chiral lipidic dialkynylcarbinol (DAC), identified as a lead for cytotoxicity against HCT116 cancer cells, is shown to typify the butadiynyl-alkynylcarbinol (BAC) unit as a new pharmacophore. The enantiomers of the internal BAC have been synthesized with 72–75% yield and 85% ee through the use of a modified Carreira reaction shown here for the first time to be compatible with butadiyne and ynal substrates. One enantiomer of the internal BAC could be characterized by X-ray crystallography. In this particular case, the ‘DAC to BAC’ ethynylogation results in a slight enhancement of the eutomer potency with a preserved vanishing eudismic ratio (IC50values from 102±14 nM to 42±12 nM for the (+) enantiomers).
- Listunov, Dymytrii,Saffon-Merceron, Nathalie,Joly, Etienne,Fabing, Isabelle,Génisson, Yves,Maraval, Valérie,Chauvin, Remi
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- Silyl Group-Directed 6-exo-dig Iodocyclization of Homopropargylic Carbamates and Amides
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Iodocyclization of silyl group-substituted homopropargylic carbamates and amides proceeded via 6-exo-dig mode to afford 6-vinylene-4,5-dihydro-1,3-oxazines in moderate to quantitative yields. This is the first report for silyl group-solely directed iodocy
- Okitsu, Takashi,Nakahigashi, Hikaru,Sugihara, Ryosuke,Fukuda, Ikki,Tsuji, Saki,In, Yasuko,Wada, Akimori
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- Signal Amplification for Imaging Mass Cytometry
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An enzyme-catalyzed reporter deposition stain has been developed for Imaging Mass Cytometry (IMC). The reagent consists of an alkaline phosphatase substrate tethered to a tellurophene which serves as reporter group for mass cytometry. Upon phosphate hydro
- Rana, Rahul,Gómez-Biagi, Rodolfo F.,Bassan, Jay,Nitz, Mark
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- KRAS G12D INHIBITORS
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The present invention relates to compounds that inhibit KRas G12D. In particular, the present invention relates to compounds that inhibit the activity of KRas G12D, pharmaceutical compositions comprising the compounds and methods of use therefor.
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Paragraph 0212
(2022/02/15)
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- Cascade Reaction to Selectively Synthesize Multifunctional Indole Derivatives by IrIII-Catalyzed C?H Activation
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An effective and condition-controlled way to synthesize with high selectivity a variety of functionalized indoles with potent biological properties has been developed. Notably, 2,4-dialkynyl indole products were obtained by direct double C?H bond alkynylation, whereas alkynyl at the C4 position could convert to carbonyl to generate 2-alkynyl-3,4-diacetyl indoles fast and effectively. Additionally, a one-pot relay catalytic reaction led to 2,5-di-alkynyl-3,4-diacetyl indoles when using a carbonyl group as the directing group and by controlling the type and quantity of additives. A possible mechanism was proposed based on many studies including deuterium-exchange experiments, the necessary conditions of product conversion, and the effect of water on the reaction.
- Chai, Xin-Yue,Xu, Hui-Bei,Dong, Lin
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supporting information
p. 13123 - 13127
(2021/08/13)
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- Rhodium(III)-Catalyzed Synthesis of Skipped Enynes via C(sp3)–H Alkynylation of Terminal Alkenes
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The RhIII-catalyzed allylic C?H alkynylation of non-activated terminal alkenes leads selectively to linear 1,4-enynes at room-temperature. The catalytic system tolerates a wide range of functional groups without competing functionalization at other positions. Similarly, the vinylic C?H alkynylation of α,β- and β,γ- unsaturated amides gives conjugated Z-1,3-enynes and E-enediynes.
- Della-Felice, Franco,Zanini, Margherita,Jie, Xiaoming,Tan, Eric,Echavarren, Antonio M.
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supporting information
p. 5693 - 5698
(2021/02/09)
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- Metal-free C8-H functionalization of quinolineN-oxides with ynamides
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The metal-free C8-H functionalization of quinolineN-oxides with ynamides is unveiled for the first time by the intramolecular Friedel-Crafts-type reaction of quinolyl enolonium intermediates generated from Br?nsted acid-catalyzed addition of quinolineN-ox
- Hu, Weican,Zhang, Feiyang,Chen, Chen,Qi, Tianhang,Shen, Yanlong,Qian, Guoying,Rong, Zhouting
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supporting information
p. 6995 - 6998
(2021/07/21)
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- KRAS G12D INHIBITORS
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The present invention relates to compounds that inhibit KRas G12D. In particular, the present invention relates to compounds that inhibit the activity of KRas G12D, pharmaceutical compositions comprising the compounds and methods of use therefor.
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Paragraph 0671
(2021/03/05)
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- Base-Mediated Generation of Ketenimines from Ynamides: [3+2] Annulation with Azaallyl Anions
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Under basic conditions and heat, ynamides can serve as precursors to ketenimines, whose synthetic potential is often hampered by their difficulty of access. Herein, we report that they can undergo a [3+2] cycloaddition with 2-azaallyl anions, obtained from benzylimines under the same reaction conditions. This reaction between two highly reactive intermediates, both generated in situ from bench stable starting materials, gives access to various nitrogen-rich heterocycles. The reaction usually proceeds with excellent diastereoselectivity, in favor of the cis adduct. Deuteration experiments and DFT calculations helped rationalize the regio- and stereoselectivity of the process as well as the formation of side products. (Figure presented.).
- D'Hollander, Agathe C. A.,Romero, Eugénie,Vijayakumar, Kamsana,Le Houérou, Camille,Retailleau, Pascal,Dodd, Robert H.,Iorga, Bogdan I.,Cariou, Kevin
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supporting information
p. 2903 - 2908
(2021/04/21)
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- Development of Axially Chiral Styrene-Type Carboxylic Acid Ligands via Palladium-Catalyzed Asymmetric C-H Alkynylation
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A weakly coordinated carboxylate-directed palladium-catalyzed atroposelective C-H alkynylation method for the development of novel axially chiral styrene-type carboxylic acids is disclosed. This transformation exhibits good yields (up to 85%), excellent enantiocontrol (up to 99% ee), and mild conditions. Notably, the synthetic utility of the resulting alkynyl carboxylic acid derivatives was demonstrated by various derivatizations as well as their potential as chiral ligands in asymmetric C-H activations.
- Cui, Ru,Jin, Ruo-Xing,Li, Fei,Li, Yan,Wang, Xi-Sheng,Wu, Bing-Bing,Wu, Tian-Rui,Yang, Chi
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supporting information
p. 8132 - 8137
(2021/11/01)
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- Room-temperature C-H bond alkynylation by merging cobalt and photocatalysts
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A new protocol is developed for the mono- and bis-ortho-C-H alkynylation of easily accessible benzamide derivatives using alkynyl bromides at room temperature by merging cobalt and photocatalysts. The diverse reactivity of various alkynyl bromides towards
- Mandal, Rajib,Barsu, Nagaraju,Garai, Bholanath,Das, Abir,Perekalin, Dmitry,Sundararaju, Basker
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supporting information
p. 12167 - 12170
(2021/11/30)
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- Alkyne Linchpin Strategy for Drug:Pharmacophore Conjugation: Experimental and Computational Realization of a Meta-Selective Inverse Sonogashira Coupling
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The late-stage functionalization (LSF) of pharmaceutical and agrochemical compounds by the site-selective activation of C-H bonds provides access to diverse structural analogs and expands synthetically-accessible chemical space. We report a C-H functionalization LSF strategy that hinges on the use of an alkyne linchpin to assemble conjugates of sp2-rich marketed pharmaceuticals and agrochemicals with sp3-rich 3D fragments and natural products. This is accomplished through a template-assisted inverse Sonogashira reaction that displays high levels of selectivity for the meta position. This protocol is also amenable to distal structural modifications of α-amino acids. The transformation of alkyne functionality to other functional groups further highlights the applicative potential. Computational and experimental mechanistic studies shed light on the detailed mechanism. Turnover-limiting 1,2-migratory insertion of the bromoalkyne coupling partner occurs after relatively fast C-H activation. While this insertion occurs unselectively, regioconvergence results from one of the adducts undergoing a 1,2-trialkylsilyl migration to form the alkynylated product. A heterobimetallic Pd-Ag transition structure is essential for product formation in the β-bromide elimination step.
- Bhowmick, Suman,Guin, Srimanta,Kumar Singh, Vikas,Maiti, Debabrata,Paton, Robert S.,Porey, Sandip,Zhang, Xinglong
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supporting information
p. 3762 - 3774
(2020/03/10)
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- Polyynes to Polycycles: Domino Reactions Forming Polyfused Chalcogenophenes
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Polyfused chalcogenophenes are prepared in one step through polyelectrophilic cyclization of polyynes using the ambiphilic reagent MeACl (A = S, Se, or Te). Up to four new rings have been generated under mild conditions, including thiophenes, selenophenes, and tellurophenes.
- Dillon, Annaliese S.,Flynn, Bernard L.
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supporting information
p. 2987 - 2990
(2020/04/09)
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- N-Ethynylation of Anilides Decreases the Double-Bond Character of Amide Bond while Retaining trans-Conformation and Planarity
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Activated amide bonds have been attracting intense attention; however, most of the studied moieties have twisted amide character. To add a new strategy to activate amide bonds while maintaining its planarity, we envisioned the introduction of an alkynyl group on the amide nitrogen to disrupt amide resonance by nN→Csp conjugation. In this context, the conformations and properties of N-ethynyl-substituted aromatic amides were investigated by DFT calculations, crystallography, and NMR spectroscopic analysis. In contrast to the cis conformational preference of N-ethyl- and vinyl-substituted acetanilides, N-ethynyl-substituted acetanilide favors the trans conformation in the crystal and in solution. It also has a decreased double bond character of the C(O)?N bond, without twisting of the amide. N-Ethynyl-substituted acetanilides undergo selective C(O)?N bond or N?C(sp) bond cleavage reactions and have potential applications as activated amides for coupling reactions or easily cleavable tethers.
- Yamasaki, Ryu,Morita, Kento,Iizumi, Hiromi,Ito, Ai,Fukuda, Kazuo,Okamoto, Iwao
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supporting information
p. 10118 - 10122
(2019/07/05)
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- Palladium-Catalyzed Carbo-Oxygenation of Propargylic Amines using in Situ Tether Formation
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1,2-Amino alcohols and α-aminocarbonyls are frequently found in natural products, drugs, chiral auxiliaries, and catalysts. This work reports a new method for the palladium-catalyzed oxyalkynylation and oxyarylation of propargylic amines. The reaction is perfectly regioselective based on the in situ introduction of a hemiacetal tether derived from trifluoroacetaldehyde. cis-Selective carbo-oxygenation was achieved for terminal alkynes, whereas internal alkynes gave trans-carbo-oxygenation products. The obtained enol ethers could be easily transformed into 1,2-amino alcohols or α-amino ketones using hydrogenation or hydrolysis, respectively.
- Greenwood, Phillip D. G.,Grenet, Erwann,Waser, Jerome
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supporting information
p. 3010 - 3013
(2019/02/07)
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- Direct Assembly of Polysubstituted Propiolamidinates via Palladium-Catalyzed Multicomponent Reaction of Isocyanides
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A straightforward approach for the assembly of different polysubstituted propiolamidnates via palladium-catalyzed multicomponent reaction of isocyanides, haloalkynes, and amines has been reported in which the C(sp)-C(sp2) and C(sp2)a
- Li, Meng,Fang, Songjia,Zheng, Jia,Jiang, Huanfeng,Wu, Wanqing
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supporting information
p. 8439 - 8443
(2019/10/16)
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- A Micellar Catalysis Strategy for Amidation of Alkynyl Bromides: Synthesis of Ynamides in Water
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Copper-catalyzed amidation of alkynyl bromides can be carried out in water for the first time, which is made possible by a micellar catalysis strategy using rosin-based surfactant APGS-550-M. The surfactant can be easily prepared from natural abundant biomass, resin acids. Studies as to substrate scope and reaction aqueous medium recycling showcase the ease and sustainability of this technology.
- Yang, Yunqin,Meng, Xiangtai,Zhu, Baolong,Jia, Ying,Cao, Xiaoji,Huang, Shenlin
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supporting information
p. 1166 - 1169
(2019/01/04)
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- Nickel-Catalyzed Reductive 1,2-Dialkynylation of Alkenes Bearing an 8-Aminoquinoline Directing Group
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An unprecedented nickel-catalyzed reductive 1,2-dialkynylation of alkenes bearing an 8-aminoquinoline directing group has been developed. This method proceeded through a migratory insertion/reductive-coupling process under mild conditions with a wide substrate scope and good functional group tolerance, providing direct access to the synthetically flexible 1,5-diynes. Moreover, the 1,2-dialkynylation products could be further converted to borate-ester- or azide-functionalized 1,5-dienes, ditriazole, β-diyne primary amide, and trisubstituted benzene.
- Pan, Rui,Shi, Cong,Zhang, Dongquan,Tian, Yang,Guo, Songjin,Yao, Hequan,Lin, Aijun
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supporting information
p. 8915 - 8920
(2019/11/14)
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- Highly Selective Syn Addition of 1,3-Diones to Internal Ynamides Catalyzed by Zinc Iodide
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1,3-Diones are already established as nucleophiles to perform additions to ynamides; the highly selective hydroalkoxylation of internal ynamides is now described. Several catalytic systems have been compared to perform this transformation, including transition-metal-based catalysts and Lewis acids. ZnI2 was found to be both very active and highly selective providing only E adducts through a syn addition. Investigation of the scope and limitations showed that this catalyst was compatible with various functional groups. In addition to seventeen examples of ynamide hydroalkoxylation, one example of ynamide hydroarylation is reported.
- Plamont, Rémi,Graux, Lionel V.,Clavier, Hervé
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supporting information
p. 1372 - 1376
(2018/04/02)
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- Diastereoselective Copper-Mediated Cross-Couplings between Stereodefined Secondary Alkylcoppers with Bromoalkynes
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A copper(I)-mediated cross-coupling of stereodefined secondary alkyllithiums with bromoalkynes provided stereodefined alkynes with high diastereoselectivity (dr up to 98:2). This cross-coupling was extended to various secondary alkyllithiums bearing a remote oxygen functionality, and the alkyne synthesis was also performed with optically enriched alkyl iodides (up to 99% ee) providing, after cross-coupling, alkynes bearing two stereocenters (dr = 93:7; up to 99% ee).
- Skotnitzki, Juri,Morozova, Varvara,Knochel, Paul
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supporting information
p. 2365 - 2368
(2018/04/30)
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- Copper-mediated synthesis of N-vinyl ynamides from N-vinyl carbamates
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Ynamides are versatile 3-atoms building blocks for organic synthesis as they participate in a variety of ionic, radical and pericyclic processes. Converting ynamides into 5-atom building blocks, such as the yet unreported N-vinyl ynamides, would open new avenues in this fascinating chemistry. We describe herein our efforts towards such goal and demonstrate that the cross-coupling between N-vinyl carbamates and bromo-alkynes using copper(I) thiophene carboxylate, 1,10-phenanthroline and tBuOK in DMSO is a reactive system with an improved profile compared to the classical ynamides syntheses. The advantages and limitations of this copper-mediated reaction are discussed.
- Le Fouler, Vincent,Duret, Guillaume,Bisseret, Philippe,Blanchard, Nicolas
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supporting information
p. 3349 - 3352
(2018/08/06)
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- Pd(ii)-Catalyzed gamma-C(sp3)-H alkynylation of amides: Selective functionalization of R chains of amides R1C(O)NHR
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The gamma C(sp3)-H bond alkynylation of R chains of amides R1C(O)NHR, a fundamental class of synthetic substrates, has not been accomplished to date. Here, the first example of palladium(ii)-catalyzed alkynylation of an unactivated gamma C(sp3)-H bond of alkyl amides (cyclic, linear, and amino acids) is reported. The kinetic experiment shows that the rate of the reaction depends on the coupling partners and the amides. Late-stage diversification of alkynylated amides was developed by utilizing amine and alkyne functionalities.
- Landge, Vinod G.,Parveen, Ayisha,Nandakumar, Avanashiappan,Balaraman, Ekambaram
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supporting information
p. 7483 - 7486
(2018/07/13)
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- Palladium-Catalyzed Carboamination of Allylic Alcohols Using a Trifluoroacetaldehyde-Derived Tether
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The selective palladium-catalyzed carboamination of allylic alcohols is reported on the basis of the use of an easily introduced trifluoroacetaldehyde-derived tether. Aminoalkynylation reactions were realized using alkynyl bromides and commercially available phosphine ligands. For aminoarylations, a new biaryl phosphine ligand, "Fu-XPhos", was introduced to overcome a competitive Heck pathway. The carboamination products were obtained in high yields and diastereoselectivity. The tether could be easily removed to give value-added amino alcohol building blocks.
- Muriel, Bastian,Orcel, Ugo,Waser, Jerome
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supporting information
p. 3548 - 3551
(2017/07/17)
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- Pd/Cu-Catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 5-vinyloxazolones
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An attractive and novel methodology involving Pd/Cu-catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 3,5-disubstituted oxazolones was developed. Under Pd(PPh3)2Cl2/CuI
- Tang, Luning,Huang, Hai,Xi, Yang,He, Guangke,Zhu, Hongjun
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p. 2923 - 2930
(2017/04/11)
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- One-Pot Three-Component Synthesis of Vicinal Diamines via In Situ Aminal Formation and Carboamination
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A synthesis of vicinal diamines via in situ aminal formation and carboamination of allyl amines is reported. Employing highly electron-poor trifluoromethyl aldimines in their stable hemiaminal form was key to enable both a fast and complete aminal formation as well as the palladium-catalyzed carboamination step. The conditions developed allow the introduction of a wide variety of alkynyl, vinyl, aryl, and hetereoaryl groups with complete regioselectivity and high diastereoselectivity. The reaction exhibits a high functional-group tolerance. Importantly, either nitrogen atom of the imidazolidine products can be selectively deprotected, while removal of the aminal tether can be achieved in a single step under mild conditions to reveal the free diamine. We expect that this work will promote the further use of mixed aminal tethers in organic synthesis.
- Orcel, Ugo,Waser, Jerome
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supporting information
p. 12881 - 12885
(2016/10/04)
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- ORGANOTELLURIUM COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF
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A compound of formula (I) as described herein and methods and uses thereof as probes in the mass tagging of biosensors or biologically active materials for use in mass cytometry analysis of tissue samples such as in the detection, labelling and quantifica
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Paragraph 00175
(2016/03/14)
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- Efficient and Flexible Synthesis of Highly Functionalised 4-Aminooxazoles by a Gold-Catalysed Intermolecular Formal [3+2] Dipolar Cycloaddition
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Oxazoles are important motifs within bioactive and functional materials. Complex, fully substituted and functionalised 4-aminooxazoles are accessed by an efficient intermolecular reaction between an ynamide and an N-acylpyridinium N-aminide in the presence of a gold catalyst. The formal [3+2] dipolar cycloaddition employs a nucleophilic nitrenoid approach to access the 1,3-N,O-dipole character in a controllable fashion. The selectivity for a cycloaddition pathway provides a stark contrast against the indiscriminate reactivity of electrophilic acyl nitrenes. Protocols for the formation of acyl-functionalised aminides are reported from accessible precursors including carboxylic esters and acids. The function of these aminides in the oxazole-forming reaction has been explored and it is shown that substantial elaboration is accommodated despite proximity to the reactive centre. As a result functional oxazole-based motifs, such as chiral oxazoles with biologically pertinent substitution patterns, are readily accessible. The use of ynamide types that are unexplored or little used in gold catalysis has been evaluated. Unusual all-heteroatom substitution patterns around the oxazole are shown to be accessible using thio-ynamides. The study shows that a close stoichiometry of reactants is suitable alongside relatively low loadings of the bench-stable precatalysts in practically straightforward multi-mmol scale reactions. The efficiency and flexibility of this regioselective intermolecular preparation is demonstrated in the ready synthesis of oxazoles with substantial structural and functional group variation.
- Gillie, Andrew D.,Jannapu Reddy, Raju,Davies, Paul W.
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supporting information
p. 226 - 239
(2016/02/14)
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- Sulfonamide-directed gold-catalyzed [2+2+2]-cycloadditions of nitriles with two discrete ynamides to construct 2,4-diaminopyridine cores
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Gold-catalyzed [2+2+2]-cycloadditions of two discrete ynamides and one nitrile afford 2,4-diaminopyridine derivatives that are not readily prepared from typical low-valent-metal catalysts. Our mechanistic analysis reveals that the reaction chemoselectivit
- Chen, Yu-Ling,Sharma, Pankaj,Liu, Rai-Shung
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supporting information
p. 3187 - 3190
(2016/02/23)
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- Cobalt-Catalyzed Bis-alkynylation of Amides via Double C-H Bond Activation
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The first example of cobalt-catalyzed selective bis-alkynylation of amides via double C-H bond activation with the directing assistance of a removable bidentate auxiliary is reported. The developed alkynylation strategy is simple, efficient, and tolerant
- Landge, Vinod G.,Jaiswal, Garima,Balaraman, Ekambaram
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supporting information
p. 812 - 815
(2016/03/01)
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- Regioselective iodoamination of terminal ynamides for the synthesis of α-amino-β,β-diiodo-enamides
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A mild and efficient methodology involving the I2/TBHP-mediated intermolecular iodoamination of ynamides with amines for the synthesis of α-amino-β,β-diiodo-enamides was developed. This reaction provides the first intermolecular iodoamination o
- Huang, Hai,Tang, Luning,Han, Xiaobo,He, Guangke,Xi, Yang,Zhu, Hongjun
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supporting information
p. 4321 - 4324
(2016/03/22)
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- Synthesis of Highly Functionalized 4-Aminoquinolines
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A diverse set of highly substituted 4-aminoquinolines was synthesized from ynamides, triflic anhydride, 2-chloropyridine, and readily accessible amides in a mild one-step procedure. Diverse products: Electrophilically activated amides easily react with sulfonyl ynamides to yield a diverse range of substituted 4-aminoquinolines. The ynamides can be easily modified by Sonogashira processes or generated from dichloroenamide precursors. Any substituent can thus be introduced at the C3 position of the quinoline. 2-ClPy=2-chloropyridine, Tf2O=triflic anhydride.
- Wezeman, Tim,Zhong, Sabilla,Nieger, Martin,Br?se, Stefan
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p. 3823 - 3827
(2016/04/05)
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- Copper(I)-Catalyzed Three-Component Click/Alkynylation: One-Pot Synthesis of 5-Alkynyl-1,2,3-triazoles
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A copper(I)-catalyzed tandem CuAAC/alkynylation reaction of various alkynes, organic azides, and bromoalkynes to provide rapid access to 5-alkynyl-1,2,3-triazoles has been developed. The reaction proceeded via a copper-catalyzed alkyne azide cycloaddition
- Wang, Weiguo,Wei, Fang,Ma, Yudao,Tung, Chen-Ho,Xu, Zhenghu
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supporting information
p. 4158 - 4161
(2016/10/11)
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- Palladium-catalyzed vicinal amino alcohols synthesis from allyl amines by in situ tether formation and carboetherification
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Vicinal amino alcohols are important structural motifs of bioactive compounds. Reported herein is an efficient method for their synthesis based on the palladium-catalyzed oxy-alkynylation, oxy-arylation, or oxy-vinylation of allylic amines. High regio- and stereoselectivity were ensured through the in situ formation of a hemiaminal tether using the cheap commercially available trifluoroacetaldehyde in its hemiacetal form. The obtained compounds are important building blocks, which can be orthogonally deprotected to give either free alcohols, amines, or terminal alkynes.
- Orcel, Ugo,Waser, Jerome
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supporting information
p. 5250 - 5254
(2015/04/27)
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- Intramolecular palladium-catalyzed alkene carboalkynylation
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Abstract Carbocycles are essential building blocks for the synthesis of natural and synthetic bioactive compounds. Herein, we report the first example of palladium-catalyzed intramolecular carboalkynylation of non-activated olefins. Using activated carbon
- Nicolai, Stefano,Swallow, Peter,Waser, Jerome
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supporting information
p. 5959 - 5964
(2015/08/03)
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- Ynamide Carbopalladation: A Flexible Route to Mono-, Bi- and Tricyclic Azacycles
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Bromoenynamides represent precursors to a diversity of azacycles by a cascade sequence of carbopalladation followed by cross-coupling/electrocyclization, or reduction processes. Full details of our investigations into intramolecular ynamide carbopalladation are disclosed, which include the first examples of carbopalladation/cross-coupling reactions using potassium organotrifluoroborate salts; and an understanding of factors influencing the success of these processes, including ring size, and the nature of the coupling partner. Additional mechanistic observations are reported, such as the isolation of triene intermediates for electrocyclization. A variety of hetero-Diels-Alder reactions using the product heterocycles are also described, which provide insight into Diels-Alder regioselectivity.
- Campbell, Craig D.,Greenaway, Rebecca L.,Holton, Oliver T.,Walker, P. Ross,Chapman, Helen A.,Russell, C. Adam,Carr, Greg,Thomson, Amber L.,Anderson, Edward A.
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supporting information
p. 12627 - 12639
(2015/09/01)
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- Copper-catalyzed N-alkynylations of sulfoximines with bromoacetylenes
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N-Alkynylated sulfoximines have been obtained by copper-catalyzed cross-coupling reactions starting from NH-sulfoximines and bromoacetylenes in moderate to good yields. The reaction conditions are mild, and the substrate scope is wide.
- Chen, Xiao Yun,Wang, Long,Frings, Marcus,Bolm, Carsten
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supporting information
p. 3796 - 3799
(2014/08/05)
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- Palladium nanoparticle-catalyzed direct ethynylation of aliphatic carboxylic acid derivatives via C(sp3)-H bond functionalization
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We have developed a sulfur-modified, gold-supported palladium material (SAuPd) with palladium, Pd, nanoparticles on its surface; it is a recyclable, low-leaching Pd catalyst. Here we report, using SAuPd, the first example of Pd nanoparticle-catalyzed, una
- Al-Amin, Mohammad,Arisawa, Mitsuhiro,Shuto, Satoshi,Ano, Yusuke,Tobisu, Mamoru,Chatani, Naoto
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supporting information
p. 1631 - 1637
(2014/06/09)
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- Pd(0)-catalyzed alkene oxy- and aminoalkynylation with aliphatic bromoacetylenes
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Tetrahydrofurans and pyrrolidines are among the most important heterocycles found in bioactive compounds. Cyclization-functionalization domino reactions of alcohols or amines onto olefins constitute one of the most efficient methods to access them. In this context, oxy- and aminoalkynylation are especially important reactions, because of the numerous transformations possible with the triple bond of acetylenes, yet these methods have been limited to the use of silyl protected acetylenes. Herein, we report the first palladium-catalyzed oxy- and aminoalkynylation using aliphatic bromoalkynes, which proceeded with high diastereoselectivity and functional group tolerance. A one-pot hydrogenation of the triple bond gave then access to alkyl-substituted tetrahydrofurans and pyrroldines. Finally, a detailed study of the side products formed during the reaction gave a first insight into the reaction mechanism.
- Nicolai, Stefano,Sedigh-Zadeh, Raha,Waser, Jeroime
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p. 3783 - 3801
(2013/06/26)
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- A highly chemoselective and practical alkynylation of thiols
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A thiol-alkynylation procedure utilizing the hypervalent iodine alkyne transfer reagent TIPS-ethynyl-benziodoxolone has been developed. This scalable reaction proceeds in five minutes at room temperature in an open flask using commercially available reagents. The scope of the reaction is broad, with a variety of phenolic, benzylic, heterocyclic, and aliphatic thiols undergoing alkynylation in excellent yield. The method is highly chemoselective as a vast array of functional groups are tolerated. The utility of the thiol-alkynylation in postsynthetic elaboration has been demonstrated through the facile installment of a fluorophore tag on a cysteine-containing peptide.
- Frei, Reto,Waser, Jeroime
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supporting information
p. 9620 - 9623
(2013/07/26)
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- Intramolecular carbocupration of N-aryl-ynamides: A modular indole synthesis
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A modular indole synthesis based on an intramolecular 5-endo-dig carbocupration starting from readily available N-aryl-ynamides is reported. A variety of ynamides are converted to indoles in moderate to good yields and with varying substitution pattern on the indole ring. This further extends the synthetic utility of ynamides in organic synthesis and provides additional insights on the use of intramolecular carbometalation reactions.
- Gati, Wafa,Couty, Francois,Boubaker, Taoufik,Rammah, Mohamed M.,Rammah, Mohamed B.,Evano, Gwilherm
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supporting information
p. 3122 - 3125
(2013/07/26)
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