- K2S2O8mediated synthesis of 5-Aryldipyrromethanes and meso-substituted A4-Tetraarylporphyrins
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The synthesis of dipyrromethanes from pyrrole and arylglyoxylic acids in the presence of K2S2O8at 90 C is reported affording dipyrromethanes in very good yields. Unlike an excess pyrrole traditionally used in dipyrromethane synthesis, the current method uses a stoichiometric amount of pyrrole avoiding any use of Br?nsted or Lewis acid. A gram scale synthesis of 5-phenyldipyrromethane is also achieved demonstrating potential scale up of dipyrromethanes using this method feasible. Subsequently, dipyrromethanes were converted to A4tetraarylporphyrins also in the presence of K2S2O8at 90C. A direct synthesis of A4-tetraphenylporphyrin from excess pyrrole and phenylglyoxylic acid in the presence of K2S2O8 at 90C is also reported.
- Laha, Joydev K.,Hunjan, Mandeep Kaur
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p. 664 - 673
(2021/06/03)
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- Preparation method for degrading impurity in ivabradine hydrochloride
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The preparation method comprises the following steps: 1) the compound 2 is subjected Riley oxidation to prepare the compound 3. 2) The compound 3 and Compound 4 were condensed in the presence of a condensing agent to give compound 5. 3) Compound 5 A compo
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Paragraph 0071-0073; 0084-0086; 0097-0099
(2021/10/11)
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- Minisci aroylation of N-heterocycles using choline persulfate in water under mild conditions
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Metal persulfate mediated thermal oxidative organic transformations invariably require a higher temperature and frequently use an organic solvent. The objective of this work was to develop persulfate mediated oxidative transformations that can be performed nearly at room temperature using water as a solvent. This report describes modified Minisci aroylation of isoquinolines with arylglyoxylic acids using choline persulfate and its pre-composition (choline acetate and K2S2O8) in water at 40 °C. A few other nitrogen heterocycles were also utilized affording various aroylated products in good to excellent yields. Unlike metal persulfate that could produce metal salt byproducts, a key feature of the chemistry reported herein includes the use of environmentally benign choline persulfate containing biodegradable choline as a counter-cation, the Minisci reaction demonstrated at 40 °C in water as the only solvent, and unconventional activation of persulfate. This journal is
- Hunjan, Mandeep Kaur,Laha, Joydev K.,Tinwala, Ummehani
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p. 22853 - 22859
(2021/12/24)
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- Diversity in Heterocycle Synthesis Using α-Iminocarboxylic Acids: Decarboxylation Dichotomy
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Despite the structural similarity with imines, α-iminocarboxylic acids have seldom been used in heterocycles synthesis. The reactions of ortho-substituted anilines and arylglyoxylic acids in DMSO at 40 °C gave various benzo-fused five- to six-membered N-heterocycles in good to excellent yields. The reaction proceeds via intramolecular Michael addition of α-iminocarboxylic acids, generated in situ, with an ortho-substituted nucleophile, yielding an isolable unprecedented tetrahedral carboxylic acids, which upon decarboxylation without any aid of additional reagents forms the N-heterocycles. DMSO is crucial in this reaction, perhaps because of improved solubility and the ease of decarboxylation of these tetrahedral carboxylic acids. However, a copper-catalyzed reaction of ortho-substituted anilines and 2-bromoarylglyoxylic acids gave a dibenzo-fused seven-membered N-heterocycle under a basic reaction condition. Unlike intramolecular cyclization with α-iminocarboxylic acids in the first case, α-iminocarboxylic acid undergoes a competitive decarboxylation under the copper-catalyzed conditions, which upon subsequent heteroarylation form the heterocycles. Taken together, the study described herein represents two different modes of decarboxylation observed with α-iminocarboxylic acids, leading to the synthesis of divergent heterocycles and pharmaceuticals, which remained unexplored previously.
- Hunjan, Mandeep Kaur,Laha, Joydev K.
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- Aroylation of Electron-Rich Pyrroles under Minisci Reaction Conditions
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The development of Minisci acylation on electron-rich pyrroles under silver-free neutral conditions has been reported featuring the regioselective monoacylation of (NH)-free pyrroles. Unlike conventional Minisci conditions, the avoidance of any acid that could result in the polymerization of pyrroles was the key to success. The umpolung reactivity of the nucleophilic acyl radical, generated in situ from arylglyoxylic acid, could help explain the mechanism of product formation with electron-rich pyrroles. Alternatively, the nucleophilic substitution of the acyl radical on the electron-deficient pyrrole radical cation is proposed.
- Laha, Joydev K.,Kaur Hunjan, Mandeep,Hegde, Shalakha,Gupta, Anjali
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supporting information
p. 1442 - 1447
(2020/02/22)
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- Palladium-Catalyzed Decarboxylative ortho-C(sp2)?H Aroylation of N-Sulfoximine Benzamides at Room Temperature
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A palladium-catalyzed method for the decarboxylative ortho C?H acylation of N-sulfoximine benzamides is developed at room temperature. The catalytic method enables easy access to various functionalized 2-aroylaromatic carboxylic acid derivatives in good isolated yields. Based on our mechanistic studies, a Pd(II)/Pd(IV) catalytic cycle that involves aroyl radical intermediate is proposed for the reaction.
- Das, Prasenjit,Biswas, Promita,Guin, Joyram
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supporting information
p. 920 - 925
(2020/03/04)
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- Intermolecular Radical Addition to Ketoacids Enabled by Boron Activation
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The intermolecular radical addition to the carbonyl group is difficult due to the facile fragmentation of the resulting alkoxyl radical. To date, the intermolecular radical addition to ketones, a valuable approach to construct quaternary carbon centers, remains a formidable synthetic challenge. Here, we report the first visible-light-induced intermolecular alkyl boronic acid addition to α-ketoacids enabled by the Lewis acid activation. The in situ boron complex formation is confirmed by various spectroscopic measurements and mechanistic probing experiments, which facilitates various alkyl boronic acid addition to the carbonyl group and prevents the cleavage of the newly formed C-C bond. Diversely substituted lactates can be synthesized from readily available alkyl boronic acids and ketoacids at room temperature merely under visible light irradiation, without any additional reagent. This boron activation approach can be extended to alkyl dihydropyridines as radical precursors with external boron reagents for primary, secondary, and tertiary alkyl radical additions. The pharmaceutically useful anticholinergic precursors are easily scaled up in multigrams under metal-free conditions in flow reactors.
- Xie, Shasha,Li, Defang,Huang, Hanchu,Zhang, Fuyuan,Chen, Yiyun
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supporting information
p. 16237 - 16242
(2019/10/14)
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- Pd(OAc)2-Catalyzed Asymmetric Hydrogenation of α-Iminoesters
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An efficient Pd(OAc)2-catalyzed asymmetric hydrogenation of α-iminoesters was realized for the first time at 1 atm hydrogen pressure and room temperature. Pd(OAc)2, a less expensive Pd salt with low toxicity, was found to be the most suitable catalyst precursor rather than Pd(TFA)2 which is usually the catalyst of choice for homogeneous asymmetric hydrogenation. The chiral α-arylglycine fragments are widely found in many chiral products and bioactive molecules.
- Chen, Jianzhong,Li, Feilong,Wang, Fang,Hu, Yawen,Zhang, Zhenfeng,Zhao, Min,Zhang, Wanbin
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supporting information
p. 9060 - 9065
(2019/11/19)
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- New method for preparing alpha-bromo-3,4-dimethoxyphenylacetic trichloroethanol ester
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The invention discloses a method for preparing a key intermediate alpha-bromo-3,4-dimethoxyphenylacetic trichloroethanol ester for synthesis of Baculiferin L. the method comprises the following steps:1) using 1,2-dimethoxylphenyl (CAS: 91-16-7) and methyl
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Paragraph 0013
(2019/01/08)
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- Umpolung Reactivity of Aldehydes toward Carbon Dioxide
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Carbon dioxide is an intrinsically stable molecule. Therefore, its activation requires extra energy input in the form of reactive reagents and/or activated catalysts and, often, harsh reaction conditions. Reported here is a direct carboxylation reaction of aromatic aldehydes with carbon dioxide to afford α-keto acids as added-value products. In situ generation of a reactive cyanohydrin was the key to the successful carboxylation reaction under operationally mild reaction conditions (25–40 °C, 1 atm CO2). The resulting α-keto acids served as a platform for α-amino acid synthesis by reductive amination reactions, illustrating the chemical synthesis of essential bioactive molecules from carbon dioxide.
- Juhl, Martin,Lee, Ji-Woong
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supporting information
p. 12318 - 12322
(2018/09/10)
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- Discovery and Optimization of Small Molecule Splicing Modifiers of Survival Motor Neuron 2 as a Treatment for Spinal Muscular Atrophy
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The underlying cause of spinal muscular atrophy (SMA) is a deficiency of the survival motor neuron (SMN) protein. Starting from hits identified in a high-throughput screening campaign and through structure-activity relationship investigations, we have developed small molecules that potently shift the alternative splicing of the SMN2 exon 7, resulting in increased production of the full-length SMN mRNA and protein. Three novel chemical series, represented by compounds 9, 14, and 20, have been optimized to increase the level of SMN protein by >50% in SMA patient-derived fibroblasts at concentrations of 160 nM. Daily administration of these compounds to severe SMA Δ7 mice results in an increased production of SMN protein in disease-relevant tissues and a significant increase in median survival time in a dose-dependent manner. Our work supports the development of an orally administered small molecule for the treatment of patients with SMA.
- Woll, Matthew G.,Qi, Hongyan,Turpoff, Anthony,Zhang, Nanjing,Zhang, Xiaoyan,Chen, Guangming,Li, Chunshi,Huang, Song,Yang, Tianle,Moon, Young-Choon,Lee, Chang-Sun,Choi, Soongyu,Almstead, Neil G.,Naryshkin, Nikolai A.,Dakka, Amal,Narasimhan, Jana,Gabbeta, Vijayalakshmi,Welch, Ellen,Zhao, Xin,Risher, Nicole,Sheedy, Josephine,Weetall, Marla,Karp, Gary M.
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supporting information
p. 6070 - 6085
(2016/07/26)
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- Copper-catalyzed direct α-ketoesterification of propiophenones with acetophenones via C(sp3)-H oxidative cross-coupling
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A novel copper-catalyzed direct α-ketoesterification of propiophenones with acetophenones via C(sp3)-H oxidative cross-coupling was developed. The reaction utilized O2 as a clean oxidant with high atom economy and the starting materials are facile and commercially available.
- Du, Juan,Zhang, Xiuli,Sun, Xi,Wang, Lei
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supporting information
p. 4372 - 4375
(2015/03/30)
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- Asymmetric friedel-crafts alkylation of α-substituted β-nitroacrylates: Access to β2,2-amino acids bearing indolic all-carbon quaternary stereocenters
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A highly enantioselective Friedel-Crafts alkylation reaction of indoles with acyclic α-substituted β-nitroacrylates is developed under the catalysis of Ni(ClO4)2-bisoxazoline complex at 1 mol % catalyst loading, affording chiral indolic β-nitroesters bearing all-carbon quaternary stereocenters in excellent yields and ees of up to 97%. Transformation of one of the products to β2,2-amino ester and tetrahydro-β-carboline through nitro reduction and sequential Pictet-Spengler cyclization was exemplified.
- Weng, Jian-Quan,Deng, Qiao-Man,Wu, Liang,Xu, Kai,Wu, Hao,Liu, Ren-Rong,Gao, Jian-Rong,Jia, Yi-Xia
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supporting information
p. 776 - 779
(2014/03/21)
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- Effective synthesis of 3,5-diaryl-(1H)-pyrazin-2-ones via microwave mediated ring closure
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In this study we report on a flexible straight forward synthesis toward novel 3,5-diaryl-(1H)-pyrazin-2-ones. Our synthetic strategy involved an acyclic di-keto derivative as key intermediate. The final pyrazin-2-one ring closure reaction was yield-optimized by using a microwave mediated procedure and ammoniumacetate as nitrogen source. Our method is a suitable alternative to palladium-catalyzed coupling reactions for the 3,5-diaryl decoration of the (1H)-pyrazin-2-one scaffold. Since the (1H)-pyrazin-2-ones is present as scaffold in a number of biologically active compounds the reported synthetic platform is a useful approach to generate a set of highly diverse 3,5-diaryl-(1H)-pyrazin-2-one compounds.
- Johannes, Eugen,Horbert, Rebecca,Schlosser, Joachim,Schmidt, Dorian,Peifer, Christian
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p. 4067 - 4072
(2013/07/26)
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- Efficient synthesis of a new structural phenanthro[9,10,3′,4′] indolizidine starting from pyrrole
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(Chemical Equation Presented) A new structural phenanthroindolizidine, 2,3,6,7-tetramethoxyphenanthro[9,10,3′,4′]indolizidine, has been synthesized efficiently from pyrrole. An important feature of this synthesis is that intramolecular oxidative coupling
- Wang, Kailiang,Wang, Qingmin,Huang, Runqiu
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p. 8416 - 8421
(2008/03/12)
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- α-Ketocarboxylic acid-based inhibitors of protein tyrosine phosphatases
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A series of aryl α-ketocarboxylic acids was synthesized and investigated as inhibitors for the protein tyrosine phosphatase from Yersinia enterocolitica. IC50 values for these compounds range from 79 to 2700 μM. Larger aromatic groups, and aromatic groups with high electron density, lead to more potent inhibitors. In general, the related aryl α-hydroxycarboxylic acids show lower activity.
- Chen, Yen Ting,Onaran,Doss, Christopher J.,Seto, Christopher T.
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p. 1935 - 1938
(2007/10/03)
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- Photochemistry of Substituted Benzoylformate Esters. A Convenient Method for the Photochemical Oxidation of Alcohols
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The production of aldehydes and ketones via photochemical hydrogen atom transfer in substituted benzoylformate esters of primary and secondary alcohols has been investigated.Substituent effect studies have shown that (2,4-dimethoxybenzoyl)formate (DMBF) esters give superior performance.A divergence in the byproducts derived from the ester group (the benzaldehyde (and presumably CO) or the benzoic acid (and presumably CO2)) is observed depending on the presence of oxygen.A mechanistic rationale for the benzoic acid has been advanced based on the known trapping of intermediate 1,4-biradicals by oxygen followed by fragmentation.
- Pirrung, Michael C.,Tepper, Ronald J.
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p. 2461 - 2465
(2007/10/02)
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- Oxidative Cyclization of Acyclic Aryl-Substituted N-Vinylurethanes
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Oxidation of the acyclic N-(1-(1-naphthyl)vinyl)urethane (3) with lead tetraacetate (LTA) forms a naphthyloxazolone as the major product, accompanied by the product of rearrangement, N-(ethoxycarbonyl)-1-naphthylacetamide.When the naphthyl group is replaced by alkoxy-substituted aromatic rings, the N-vinylurethane undergoes three successive oxidations by LTA leading to novel substituted nitrogen containing cyclic anhydrides, oxazolidine-2,5-diones.The structure of this unusual oxidation product was proven by X-ray analysis.The mechanism of the oxidation is discussed in terms of known enamide oxidations, and the intermediacy of an oxazolone is demonstrated.
- Lenz, George R.,Costanza, Carl,Lessor, Ralph A.,Ezell, Edward F.
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p. 1753 - 1757
(2007/10/02)
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- Electro-organic Reactions. Part 22. An Entry into the Quinolizidine and Benzoquinolizidine Ring Systems via Anodic Methoxylation
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Examples of the quinolizidine and benzoquinolizidine ring systems (1,1-bisethoxycarbonyl-4-oxo-quinolizidine, 1,3,4,6,7,11b-hexahydro-2H-benzoquinolizidine, and 1,2-t-butyl-3,4,6,7,11b-hexahydro-2H-benzo-quinolizidine) have been synthesized by routes which involve initial anodic methoxylation of piperidine precursors with subsequent intramolecular Lewis acid-catalysed cyclisation reactions.Reaction conditions for such cyclisations have been explored; success depends on a correct choice of catalyst (usually aluminium chloride) and, critically, on steric factors.The stereochemistry of the cyclic products has been established and the stereochemical course of the reactions is commented upon.
- Palasz, Peter D.,Utley, James H. P.,Hardstone, J. David
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p. 281 - 292
(2007/10/02)
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- MANASSANTINS A/B AND SAUCERNEOL: NOVEL BIOLOGICALLY ACTIVE LIGNOIDS FROM SAURURUS CERNUUS
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From the extract of Saururus cernuus two toxic principles, manassantins A and B and a related substance, saucerneol, were isolated.They have novel dineolignan or sesquineolignan type structures.Although toxic, manassantin A showed potential neuroleptic activity.
- Rao, Koppaka V.,Alvarez, Francisco M.
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p. 4947 - 4950
(2007/10/02)
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