- Efficiency Enhancement of a Photocatalytic Decarbonylation of an Aminocyclopropenone by Benzothiophene Substitution
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To improve the efficiency of the photocatalytic decarbonylation of cyclopropenones, the effects of substituents on cyclopropenone were explored. A benzothiophene-substituted aminocyclopropenone exhibited significantly improved decarbonylation efficiency t
- Mishiro, Kenji,Nomura, Mitsuki,Furuyama, Taniyuki,Kunishima, Munetaka
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p. 3625 - 3636
(2021/03/03)
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- Synthesis of Aliphatic Amides through a Photoredox Catalyzed Radical Carbonylation Involving Organosilicates as Alkyl Radical Precursors
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Alkyl radicals, from primary to tertiary, formed by photocatalyzed oxidation of organosilicates, are involved efficiently in radical carbonylation with carbon monoxide (CO), in the presence of various amines and CCl4, leading to a variety of amides in moderate to good yields. (Figure presented.).
- Cartier, Alex,Levernier, Etienne,Dhimane, Anne-Lise,Fukuyama, Takahide,Ollivier, Cyril,Ryu, Ilhyong,Fensterbank, Louis
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p. 2254 - 2259
(2020/05/06)
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- Phototriggered Active Alkyne Generation from Cyclopropenones with Visible Light-Responsive Photocatalysts
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A photocatalytic active alkyne generation reaction was developed using cyclopropenone as a starting reagent. Visible light-responsive photocatalysts induced cyclopropenone decarbonylation. The resulting highly reactive alkyne could be used directly, witho
- Mishiro, Kenji,Kimura, Takeshi,Furuyama, Taniyuki,Kunishima, Munetaka
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supporting information
p. 4101 - 4105
(2019/06/17)
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- Facile direct synthesis of amides from trichloroethyl esters using catalytic DBU
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A practical method for the direct synthesis of amide compounds is described. Using small quantities of DBU as a catalyst, the direct conversion of 2,2,2-trichloroethyl esters to their corresponding amides was readily achieved. Based on this protocol, various amide compounds were successfully synthesized in high yield, suggesting a promising approach for the practical one-pot aminolysis from 2,2,2-trichloroethyl protected esters.
- La, Minh Thanh,Kim, Hee-Kwon
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p. 1135 - 1141
(2018/11/25)
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- Direct Amidation of Carboxylic Acids through an Active α-Acyl Enol Ester Intermediate
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The development of a highly efficient and simple protocol for the direct amidation of carboxylic acids is described employing ynoates as novel coupling reagents. The transformation proceeds in good to excellent yields via in situ α-acyl enol ester intermediates formation under mild reaction conditions. This useful method has been demonstrated for a range of substrates to provide a succinct access to structurally diverse amides, including key intermediates of glibenclamide, tiapride hydrochloride, and nateglinide, and can be conducted on a mole scale.
- Xu, Xianjun,Feng, Huangdi,Huang, Liliang,Liu, Xiaohui
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p. 7962 - 7969
(2018/06/18)
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- Design, Synthesis, and Biological Evaluation of Tetrahydroisoquinoline-Based Histone Deacetylase 8 Selective Inhibitors
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Histone deacetylase 8 (HDAC8) is a promising drug target for multiple therapeutic applications. Here, we describe the modeling, design, synthesis, and biological evaluation of a novel series of C1-substituted tetrahydroisoquinoline (TIQ)-based HDAC8 inhibitors. Minimization of entropic loss upon ligand binding and use of the unique HDAC8 "open" conformation of the binding site yielded a successful strategy for improvement of both HDAC8 potency and selectivity. The TIQ-based 3g and 3n exhibited the highest 82 and 55 nM HDAC8 potency and 330- and 135-fold selectivity over HDAC1, respectively. Selectivity over other class I isoforms was comparable or better, whereas inhibition of HDAC6, a class II HDAC isoform, was below 50% at 10 μM. The cytotoxicity of 3g and 3n was evaluated in neuroblastoma cell lines, and 3n displayed concentration-dependent cytotoxicity similar to or better than that of PCI-34051. The selectivity of 3g and 3n was confirmed in SH-SY5Y cells as both did not increase the acetylation of histone H3 and α-tubulin. Discovery of the novel TIQ chemotype paves the way for the development of HDAC8 selective inhibitors for therapeutic applications.
- Taha, Taha Y.,Aboukhatwa, Shaimaa M.,Knopp, Rachel C.,Ikegaki, Naohiko,Abdelkarim, Hazem,Neerasa, Jayaprakash,Lu, Yunlong,Neelarapu, Raghupathi,Hanigan, Thomas W.,Thatcher, Gregory R. J.,Petukhov, Pavel A.
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p. 824 - 829
(2017/08/16)
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- Phototriggered Dehydration Condensation Using an Aminocyclopropenone
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A phototriggered dehydration condensation using an aminocyclopropenone has been developed. The UV irradiation of an aminocyclopropenone generated a highly reactive ynamine in situ and the dehydration condensation of a carboxylic acid and an amine coexisting in the reaction solution smoothly proceeded to afford an amide. This reaction is completely controllable by the ON/OFF states of a UV lamp.
- Mishiro, Kenji,Yushima, Yuki,Kunishima, Munetaka
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supporting information
p. 4912 - 4915
(2017/09/23)
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- Identification of an Imine Reductase for Asymmetric Reduction of Bulky Dihydroisoquinolines
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A new imine reductase from Stackebrandtia nassauensis (SnIR) was identified, which displayed over 25- to 1400-fold greater catalytic efficiency for 1-methyl-3,4-dihydroisoquinoline (1-Me DHIQ) compared to other imine reductases reported. Subsequently, an efficient SnIR-catalyzed process was developed by simply optimizing the amount of cosolvent, and up to 15 g L-1 1-Me DHIQ was converted completely without a feeding strategy. Furthermore, the reaction proceeded well for a panel of dihydroisoquinolines, affording the corresponding tetrahydroisoquinolines (mostly in S-configuration) in good yields (up to 81%) and with moderate to excellent enantioselectivities (up to 99% ee).
- Li, Hao,Tian, Ping,Xu, Jian-He,Zheng, Gao-Wei
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supporting information
p. 3151 - 3154
(2017/06/23)
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- Nickel/Photoredox-Catalyzed Amidation via Alkylsilicates and Isocyanates
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A nickel/photoredox, dual-catalyzed amidation reaction between alkylsilicate reagents and alkyl/aryl isocyanates is reported. In contrast to the previously reported reductive coupling process, this protocol is characterized by mild reaction conditions and the absence of a stoichiometric reductant. A mechanistic hypothesis involving a nickel-isocyanate adduct is proposed based on literature precedent and further validation by experimental results.
- Zheng, Shuai,Primer, David N.,Molander, Gary A.
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p. 7957 - 7961
(2017/11/10)
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- Mild Amide-Cleavage Reaction Mediated by Electrophilic Benzylation
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An extremely mild method for amide-cleavage by using the triazine-based benzylating reagent 4-(4,6-diphenoxy-1,3,5-triazin-2-yl)-4-benzylmorpholinium trifluoromethanesulfonate (DPT-BM), which spontaneously releases benzyl cation species when being dissolved at room temperature, has been developed. O-Benzylation of the amide with DPT-BM and the subsequent hydrolysis of the resulting intermediate benzyl imidate salt afford the corresponding amine and benzyl ester, which can be converted by hydrogenolysis into a carboxylic acid under neutral conditions. O-Benzylation proceeds depending on both steric and electronic factors around the amide group. Thus, some amides have been selectively cleaved over other amides. Furthermore, intramolecular chemoselective cleavage of an amide group in the presence of an ester group was achieved. Such selective hydrolytic reactions cannot be performed with Meerwein reagents as well as under acidic or basic hydrolytic conditions.
- Yamada, Kohei,Karuo, Yukiko,Tsukada, Yuichi,Kunishima, Munetaka
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supporting information
p. 14042 - 14047
(2016/09/21)
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- Mild and Low-Pressure fac-Ir(ppy)3-Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible-Light Photoredox Catalysis
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A novel, mild and facile preparation of alkyl amides from unactivated alkyl iodides employing a fac-Ir(ppy)3-catalyzed radical aminocarbonylation protocol has been developed. Using a two-chambered system, alkyl iodides, fac-Ir(ppy)3, amines, reductants, and CO gas (released ex situ from Mo(CO)6), were combined and subjected to an initial radical reductive dehalogenation generating alkyl radicals, and a subsequent aminocarbonylation with amines affording a wide range of alkyl amides in moderate to excellent yields.
- Chow, Shiao Y.,Stevens, Marc Y.,?kerbladh, Linda,Bergman, Sara,Odell, Luke R.
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supporting information
p. 9155 - 9161
(2016/07/14)
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- A Titanium(III)-Catalyzed Reductive Umpolung Reaction for the Synthesis of 1,1-Disubstituted Tetrahydroisoquinolines
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A catalytic reductive C1-acylation of 3,4-dihydroisoquinolines is presented that gives direct access to 1,1-disubstituted tetrahydroisoquinolines. The reaction is a titanium(III)-catalyzed reductive umpolung process in which nitriles act as effective acylation agents. The method is highly chemo- and regioselective and is demonstrated in 20 examples. It is well-suited for the large-scale synthesis of functionalized tetrahydroisoquinoline products, which is exemplified in the form of a six-step synthesis of (±)-3-demethoxyerythratidinone. (Figure Presented).
- Luu, Hieu-Trinh,Wiesler, Stefan,Frey, Georg,Streuff, Jan
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supporting information
p. 2478 - 2481
(2015/05/27)
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- TEMPO-Catalyzed Oxidative Amidation of Alcohols via Hexafluoroisopropyl Esters
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Stepwise oxidative amidation of alcohols using trichloroisocyanuric acid, a catalytic amount of TEMPO in combination with pyridine and hexafluoroisopropyl (HFIP) alcohol followed by amines is described. This procedure used HFIP esters as activating esters which were found to be very efficient acylating agents for amide bond formation. This process is compatible with a number of functional groups and acid-sensitive protecting groups.
- Vatèle, Jean-Michel
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p. 2280 - 2284
(2015/09/28)
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- Amidation of aldehydes and alcohols through α-iminonitriles and a sequential oxidative three-component strecker reaction/thio-michael addition/alumina-promoted hydrolysis process to access β-mercaptoamides from aldehydes, amines, and thiols
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Mild and general alumina-promoted hydrolysis conditions for converting α-iminonitriles into carboxamides have been developed. In combination with the oxidative three-component Strecker reaction, the one-pot direct amidation of aldehydes and alcohols is reported. Subsequently, an Yb(OTf) 3-catalyzed Michael addition of thiols to α,β-unsaturated α-iminonitriles is reported for the synthesis of β-mercapto-α- iminonitriles. The successful integration of an oxidative Strecker reaction, thio-Michael addition, and neutral-alumina-promoted hydrolysis of β-mercapto-α-iminonitriles into a three-component one-pot process allowed us to develop the direct conversion of amines, aldehydes, and thiols into β-mercaptoamides. All of these procedures were applicable to aromatic and aliphatic amines and aldehydes. First direct: The direct amidation reactions of aldehydes and alcohols were performed in combination with the oxidative three-component synthesis of α-iminonitriles. In addition, β-mercaptoamides were readily accessed from α,β-unsaturated aldehydes, amines, and thiols by a sequential process that involved a three-component Strecker reaction, Yb(OTf)3-catalyzed thio-Michael addition, and hydrolysis of the resulting β-mercapto-α-iminonitriles (see scheme). Copyright
- Gualtierotti, Jean-Baptiste,Schumacher, Xavier,Fontaine, Patrice,Masson, Géraldine,Wang, Qian,Zhu, Jieping
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supporting information
p. 14812 - 14819
(2013/01/15)
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- Aerobic amide bond formation with N-hydroxysuccinimide
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Breathe easy: Molecular oxygen is one of the most abundant, atom-efficient, and economical oxidants. An aerobic oxidative amide formation from aldehydes and amines is reported. The method uses a catalytic amount of Co(OAc) 2 and N-hydroxysuccinimide as reaction promoters. It is applicable to chiral substrates without loss of their optical purity. Copyright
- Yao, Haoyi,Yamamoto, Kana
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supporting information; experimental part
p. 1542 - 1545
(2012/09/08)
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- A highly efficient and enantioselective access to tetrahydroisoquinoline alkaloids: Asymmetric hydrogenation with an iridium catalyst
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Efficient and enantioselective: Using the iodine-bridged dimeric iridium complex [{Ir(H)[(S,S)-(f)-binaphane]}2(μ-I)3] +I- (1) a wide range of tetrahydroisoquinoline alkaloids, including the substructure of the pharmaceutical drug solifenacin, were obtained with excellent enantioselectivities and high turnover numbers (see scheme). Copyright
- Chang, Mingxin,Li, Wei,Zhang, Xumu
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supporting information; experimental part
p. 10679 - 10681
(2011/12/05)
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- An improved method of amide synthesis using acyl chlorides
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A simple, mild and highly efficient condition for amide synthesis from acyl chlorides has been developed to minimize hydrolysis, racemization and other side reactions. This method should expand capabilities in the peptide coupling area.
- Zhang, Li,Wang, Xiao-jun,Wang, Jing,Grinberg, Nelu,Krishnamurthy, DhileepKumar,Senanayake, Chris H.
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supporting information; experimental part
p. 2964 - 2966
(2009/08/07)
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- Tetrabenzylpyrophosphate: An efficient catalyst for the synthesis of carboxamides from carboxylic acids and amines
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An efficient method for the synthesis of simple and sterically hindered carboxamides from various carboxylic acids and amines using tetrabenzylpyrophosphate (TBPP) as a coupling agent in the presence of 4-(dimethylamino)pyridine (DMAP) is described. The r
- Thirupathi Reddy,Narsimha Reddy,Raghotham Reddy,Crooks, Peter A.
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p. 528 - 529
(2008/09/21)
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- The conversion of carboxylic acids into amides via NCS/triphenylphosphine
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Amides can be generated in very high yields under mild conditions from the corresponding carboxylic acid and amine in the presence of equivalent amounts of triphenylphosphine and N-halosuccinimides, e.g., NCS or NBS.
- Froyen
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p. 959 - 968
(2007/10/02)
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- Phencyclidine-like Effects of Tetrahydroisoquinolines and Related Compounds
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A series of 1,2,3,4-tetrahydroisoquinolines, tetrahydrothienopyridines, and related compounds were evaluated for their ability to inhibit binding of -1--N-allylnormetazocine to phencyclidine (PCP) and ? receptors, respectively.A representative series of compounds was evaluated in behavioral assays to determine the ability of the compounds to induce PCP-like stereotyped behavior and ataxia.All of the compounds caused stereotyped behavior and ataxia, indicating their agonist actions at the PCP site.
- Gray, Nancy M.,Cheng, Brian K.,Mick, Stephen J.,Lair, Cecelia M.,Contreras, Patricia C.
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p. 1242 - 1248
(2007/10/02)
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