40682-54-0Relevant articles and documents
Synthesis of highly substituted pyrrolidines through 1,3-dipolar cycloaddition reaction of N-metalated azomethine ylides with triarylideneacetylacetone as dipolarophile using titanocene dichloride
Murugan, Ramalingam,Raghunathan,Narayanan, S. Sriman
, p. 1936 - 1948 (2009)
The 1,3-dipolar cycloaddition reaction of tryarylideneacetyacetone derivatives with N-metalated azomethine ylides in the presence of titanocene dichloride and triethylamine has been investigated. This two-step synthetic sequence is very efficient and yielded the highly substituted pyrrolidines in good yields. The structure and stereochemistry of one of the products has been established by single-crystal x-ray structure and spectroscopic techniques.
Nucleophilic reactivities of Schiff base derivatives of amino acids
Timofeeva, Daria S.,Ofial, Armin R.,Mayr, Herbert
supporting information, p. 459 - 463 (2019/01/04)
Treatment of α-imino esters derived from glycine esters and benzophenone or benzaldehydes with potassium tert butoxide in DMSO gave persistent solutions of carbanions at 20 °C. The kinetics of their reactions with quinone methides and benzylidene malonates (reference electrophiles) have been followed photometrically under pseudo-first order conditions. The reactions followed second-order rate laws. Since addition of 18-crown-6 ether did not affect the reaction rates, the measured rate constants correspond to the reactions of the non-paired carbanions. Plots of the second-order rate constants against the electrophilicity parameters E of the electrophiles are linear, which allowed us to derive the nucleophile-specific parameters N and sN, according to the linear Gibbs energy relationship lg k2(20 °C) = sN(N + E). The Ph2C = N- and PhCH = N- groups act as very weak electron acceptors with the consequence that Ph2C = N-CH–-CO2R and PhCH = N-CH–-CO2R have a similar nucleophilicity as Ph-CH–-CO2Et, the anion of ethyl phenylacetate.
Well-Designed Phosphine-Urea Ligand for Highly Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition of Methacrylonitrile: A Combined Experimental and Theoretical Study
Xiong, Yang,Du, Zhuanzhuan,Chen, Haohua,Yang, Zhao,Tan, Qiuyuan,Zhang, Changhui,Zhu, Lei,Lan, Yu,Zhang, Min
supporting information, p. 961 - 971 (2019/01/14)
A novel chiral phosphine-urea bifunctional ligand has been developed for Cu-catalyzed asymmetric 1,3-dipolar cycloaddition of iminoesters with methacrylonitrile, a long-standing challenging substrate in asymmetric catalysis. Distortion-interaction energy analysis based on density functional theory (DFT) calculations reveals that the distortion energy plays an important role in the observed enantioselectivity, which can be attributed to the steric effect between the phosphine ligand and the dipole reactant. DFT calculations also indicate that nucleophilic addition is the enantioselectivity-determining step and hydrogen bonding between the urea moiety and methacrylonitrile assists in control of the diastereo- and enantioselectivity. By a combination of metal catalysis and organocatalysis, excellent diastereo- and enantioselectivities (up to 99:1 diastereomeric ratio, 99% enantiomeric excess) as well as good yields are achieved. A wide range of substitution patterns of both iminoester and acrylonitrile is tolerated by this catalyst system, providing access to a series of highly substituted chiral cyanopyrrolidines with up to two quaternary stereogenic centers. The synthetic utility is demonstrated by enantioselective synthesis of antitumor agent ETP69 with a pivotal nitrile pharmacophore and an all-carbon quaternary stereogenic center.
Application of the Cu(i)/TEMPO/O2 catalytic system for aerobic oxidative dehydrogenative aromatization of pyrrolidines
Luo, Zheng,Liu, Yan,Wang, Chao,Fang, Danjun,Zhou, Junyu,Hu, Huayou
supporting information, p. 4609 - 4613 (2019/09/09)
A Cu(i)/TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)-catalyzed aerobic oxidative dehydrogenative aromatization reaction of fully saturated pyrrolidines to synthesize multi-substituted pyrroles was developed for the first time. The use of a non-precious metal catalyst, green oxidant and environmentally friendly solvent made the reaction more sustainable.
An efficient and facile access to highly functionalized pyrrole derivatives
Gao, Meng,Zhao, Wenting,Zhao, Hongyi,Lin, Ziyun,Zhang, Dongfeng,Huang, Haihong
supporting information, p. 884 - 890 (2018/04/27)
A straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with N-alkyl maleimide, followed by readily complete oxidation with DDQ, has been successfully developed. Further transformation with alkylamine/sodium alkoxide alcohol solution conveniently afforded novel polysubstituted pyrroles in good to excellent yields. This methodology for highly functionalized pyrroles performed well over a broad scope of substrates. It is conceivable that this efficient construction method for privileged pyrrole scaffolds could deliver more active compounds for medicinal chemistry research.
Tandem nucleophilic addition-cycloaddition of arynes with α-iminoesters: Two concurrent pathways to imidazolidines
Jia, Hao,Guo, Zhenyan,Liu, Honglei,Mao, Biming,Shi, Xueyan,Guo, Hongchao
supporting information, p. 7050 - 7053 (2018/07/05)
The tandem nucleophilic addition-cycloaddition reaction has been developed for the synthesis of functionalized imidazolidine derivatives. A variety of α-iminoesters and aryne precursors were well tolerated under the mild reaction conditions. This asymmetric cycloaddition afforded imidazolidine derivatives with high yields, complete regioselectivities, and excellent diastereo- and enantioselectivities. Aryne-induced ylides working as 1,3-dipoles for asymmetric cycloaddition are the notable feature of the present reaction. In the tandem reaction, the [3+2] cycloaddition of aryne-induced ylides with metallized α-iminoesters and metal-catalyzed [3+2] cycloaddition of azomethine ylide with α-iminoesters are two concurrent pathways to imidazolidines.
Tandem [3 + 2] cycloaddition/1,4-addition reaction of azomethine ylides and aza-o-quinone methides for asymmetric synthesis of imidazolines
Jia, Hao,Liu, Honglei,Guo, Zhenyan,Huang, Jiaxing,Guo, Hongchao
supporting information, p. 5236 - 5239 (2017/11/06)
An enantioselective synthesis of biologically important imidazolidines has been achieved via a tandem [3 + 2] cycloaddition/1,4-addition reaction of azomethine ylide and aza-o-quinone methides. With the use of this tool, various imidazolidine derivatives are obtained in good yields with excellent diastereoselectivities and enantioselectivities.
COMPOUNDS AS HEPATITIS C INHIBITORS AND USES THEREOF IN MEDICINE
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Paragraph 00172, (2016/09/22)
Provided herein are compounds as hepatitis C inhibitors and uses thereof in medicine. Specifically, provided herein is a compound of Formula (I) or a stereoisomer, a tautomer, an enantiomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or hepatitis C diseases. Also provided herein are a pharmaceutically acceptable composition containing such compound and a method of treating HCV infection or hepatitis C diseases comprising administering the compound or pharmaceutical composition thereof disclosed herein.
Synthesis method of (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate
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Paragraph 0015; 0016; 0017, (2016/10/09)
The invention belongs to the technical field of preparation of anti hepatitis C virus drug intermediates and particularly relates to a synthesis method of (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate. The synthesis method comprises the specific steps that step one, benzaldehyde, glycine ethyl ester hydrochloride, toluene and triethylamine are used as raw materials to be synthesized into a compound 4; step two, the compound 4 and trans-1,4-dibromo butene react in the toluene and sodium ethoxide to prepare a compound 3; step three, the compound 3 and (2S)-2-[(3,5-dichlorobenzoyl peroxide) oxy] propionic acid react in the toluene, and then isopropyl alcohol and hexane are added to obtain a compound 2; step four, the compound 2 reacts with sodium hydroxide in the toluene to obtain a compound (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate. The synthesis method is simple in operation and suitable for industrialized production, the raw materials are cheap and easy to obtain, and the obtained target product is high in purity and chiral purity.
Diastereoselective Trifluoroacetylation of Highly Substituted Pyrrolidines by a Dakin-West Process
Baumann, Marcus,Baxendale, Ian R.
, p. 11898 - 11908 (2016/12/09)
A robust approach allowing for the efficient trifluoroacetylation of a series of highly substituted pyrrolidines in a diastereoselective manner is reported. The transformation is based on a Dakin-West reaction of advanced pyrrolidine 2-carboxylic acid derivatives that can be assembled stereoselectively in four synthetic steps. Importantly, this work demonstrates how the introduction of lateral substituents on the pyrrolidine scaffold enables the generation of the desired trifluoroacetylation products, which was not possible previously due to the exclusive formation of trifluoromethylated oxazoles (vide infra). In the course of this work we succeeded for the first time in isolating and characterizing (HRMS, IR, 1H, 13C and 19F NMR, X-ray) different intermediates of the Dakin-West reaction allowing us to probe its mechanism.
