- A powerful azomethine ylide route mediated by TiO2photocatalysis for the preparation of polysubstituted imidazolidines
-
Lewis- and Br?nsted-acid catalyzed 1,3-dipolar cycloaddition between azomethine ylides and unsaturated compounds is an important strategy to construct five-membered N-heterocycles. However, such a catalytic route usually demands substrates with an electron-withdrawing group (EWG) to facilitate the reactivity. Herein, we report a TiO2photocatalysis strategy that can conveniently prepare five-membered N-heterocyclic imidazolidines from a common imine (N-benzylidenebenzylamine) and alcohols along the route of 1,3-dipolaron azomethine ylide but without pre-installed EWG substituents on the substrates. Our EPR results uncovered the previously unknown mutual interdependence between an azomethine ylide and TiO2photo-induced hvb+/ecb?pair. This transformation exhibited a broad scope with 21 successful examples and could be scaled up to the gram level.
- Liu, Anan,Ma, Dongge,Qian, Yuhang,Li, Jundan,Zhai, Shan,Wang, Yi,Chen, Chuncheng
-
-
Read Online
- Sequential [6+2], [2+2], and [3+2] annulations for rapid assembly of multiple fragments
-
Assembly of four components through sequential [6+2], [2+2], and [3+2] annulations on an azulenone manifold allows for five-step access to a natural product-inspired scaffold with exquisite control of the ten consecutive stereocenters. X-ray analysis was used to define the spatial arrangement of the three fragments and functional groups on this rigid scaffold. The Royal Society of Chemistry.
- Mahendar, Velisoju,Oikawa, Hideaki,Oguri, Hiroki
-
-
Read Online
- Highly diastereoselective multicomponent synthesis of unsymmetrical imidazolines.
-
We report here a highly diastereoselective multicomponent synthesis of imidazolines. These low molecular weight scaffolds contain a four-point diversity applicable to alkyl, aryl, acyl, and hetereocyclic substitutions. [structure: see text]
- Peddibhotla, Satymaheshwar,Jayakumar,Tepe, Jetze J
-
-
Read Online
- Novel asymmetric synthesis of spiroindene-1,3dione-pyrrolidines via CoII/amino acids complex catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides and 2-arylidenindane-1,3-diones
-
Cobalt II(L-phenylalanine)2 was used effectively for the first time in a catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with 2-arylidenindane-1,3-diones, affording a series of novel spiropyrrolidine derivatives with good to
- Bdiri, Bilel,Zhou, Zhi-Ming
-
-
Read Online
- Silver-Mediated [3 + 2] Cycloaddition of Azomethine Ylides with Trifluoroacetimidoyl Chlorides for the Synthesis of 5-(Trifluoromethyl)imidazoles
-
A silver-mediated [3 + 2] cycloaddition of azomethine ylides with trifluoroacetimidoyl chlorides for the rapid assembly of 5-(trifluoromethyl)imidazoles has been developed. Notable features of the reaction include readily accessible reagents, a broad substrate scope, and high efficiency. The protocol can be successfully applied to construct the analogue of the specific allosteric modulator of GABAA receptors. The silver species could be recycled by a simple operation.
- Yang, Hefei,Lu, Shu-Ning,Chen, Zhengkai,Wu, Xiao-Feng
-
supporting information
p. 4361 - 4370
(2021/03/09)
-
- Copper/GanPhos-Catalyzed 1,3-Dipolar Cycloaddition of Azo?-methine Ylides: An Efficient Access to Chiral Pyrrolidine Spirocycles
-
A highly efficient copper/GanPhos-catalyzed 1,3-dipolar cyclo?-addition?-of azomethine ylides is reported. This viable transformation provides a series of optically active spiro[dihydronaphthalene-2,3′-pyrrolidine]s, bearing one spiro quaternary and three tertiary stereogenic centers, in good yields and with high ee values. This protocol features high diastereo- A nd enantioselectivity, broad substrate scope and mild reaction conditions.
- Gan, Zhenjie,Li, Ke,Zhang, Hui,Li, Er-Qing
-
supporting information
p. 1331 - 1340
(2020/11/30)
-
- Silver/palladium relay catalyzed 1,3-dipole annulation/allylation reactions to access fully substituted allyl imidazolidines
-
A silver/palladium relay catalyzed 1,3-dipole annulation/allylation reaction of iminoesters and Baylis-Hillman acetates for the construction of fully substituted allyl imidazolidines is reported. The reaction of both iminoesters and Baylis-Hillman acetate
- Han, Ruiping,Ding, Yue,Jin, Xueke,Li, Er-Qing
-
supporting information
p. 646 - 649
(2020/02/11)
-
- Tunable Synthesis of α-Amino Boronic Esters from Available Aldehydes and Amines through Sequential One-Pot Dehydration and Copper-Catalyzed Borylacylation
-
Copper-catalyzed multicomponent borylacylation of imines with acid chlorides and bis(pinacolato)diboron was developed for the preparation of synthetically useful and pharmacologically relevant α-amino boronic acid derivatives. Starting from a range of acid chlorides and imines with aryl, heteroaryl, and alkyl substituents, most of these ligand-free reactions proceeded smoothly at room temperature in moderate to good yields. Furthermore, a facile and convenient one-pot, multistep access to the direct synthesis of α-amino boronic acid derivatives from available aldehydes and amines was also developed.
- Xia, Qi,Chang, Hua-Rong,Li, Juan,Wang, Jia-Yi,Peng, Yan-Qing,Song, Gong-Hua
-
p. 2716 - 2724
(2020/01/31)
-
- Boron Dipyrromethene (BODIPY) as Electron-Withdrawing Group in Asymmetric Copper-Catalyzed [3+2] Cycloadditions for the Synthesis of Pyrrolidine-Based Biological Sensors
-
In this work, we describe the use of Boron Dipyrromethene (BODIPY) as electron-withdrawing group for activation of double bonds in asymmetric copper-catalyzed [3+2] cycloaddition reactions with azomethine ylides. The reactions take place under smooth conditions and with high enantiomeric excess for a large number of different substituents, pointing out the high activation of the alkene by using a boron dipyrromethene as electron-withdrawing group. Experimental, theoretical studies and comparison with other common electron-withdrawing groups in asymmetric copper-catalyzed [3+2] cycloadditions show the reasons of the different reactivity of the boron dipyrromethene derivatives, which can be exploited as a useful activating group in asymmetric catalysis. Additional experiments show that the so obtained pyrrolidines can be employed as biocompatible biosensors, which can be located in the endosomal compartments and do not present toxicity in three cell lines. (Figure presented.).
- Alemán, José,Asenjo-Pascual, Juan,Cordani, Marco,Díaz-Tendero, Sergio,Fraile, Alberto,Martín-Somer, Ana,Milán Rois, Paula,Rigotti, Thomas,Somoza, álvaro
-
supporting information
(2020/02/20)
-
- Copper(i)/Ganphos catalysis: enantioselective synthesis of diverse spirooxindoles using iminoesters and alkyl substituted methyleneindolinones
-
A copper-catalyzed asymmetric 1,3-dipolar cycloaddition of glycine iminoesters with alkyl substituted 3-methylene-2-oxindoles is described. By usingde novodesign of P-stereogenic phosphines as ligands, spiro[pyrrolidin-3,3'-oxindole]s are generated in good to excellent yields with high asymmetric induction. A further reduced catalyst loading of 0.1 mol% is sufficient to achieve a satisfactory enantioselectivity of 90% ee. The DFT calculations suggest the second Michael addition of the 1,3-dipole to be the rate- andenantio-determining step. A key feature of this 1,3-dipolar cycloaddition is the wide substrate applicability, even with alkyl aldehyde-derived azomethine ylide; thus it has streamlined a highly enantioselective access to a new class of antiproliferative agents, MDM2-p53.
- Cui, Hao,Duan, Zheng,Li, Er-Qing,Li, Ke,Mathey, Fran?ois,Song, Manman,Wang, Congcong,Wang, Yue,Wei, Donghui
-
supporting information
p. 3740 - 3746
(2020/06/03)
-
- 1,3-Dipolar Cycloadditions of Stabilized Azomethine Ylides and Electrophilic Alkenes Mediated by a Recyclable TSIL·AgOAc Catalyst
-
The synthesis of a task-specific ionic liquid (TSIL) based on a BMIM ionic liquid phosphane is achieved by modification of the original procedure. It is used as a ligand with AgOAc, and the resulting complex is fully characterized. This catalytic system promotes the 1,3-dipolar cycloaddition of stabilized azomethine ylides and electrophilic alkenes using a green methodology. The green character was analyzed using an overall set of parameters finding the optimal conditions and individualized separation/purification methods for each cycloadduct. The determination of the most important green metrics is reported in this survey, demonstrating the value of this methodology on a laboratory scale or even at an industrial level.
- Lledó, David,Grindlay, Guillermo,Sansano, José Miguel
-
supporting information
p. 4095 - 4100
(2019/06/25)
-
- Multilayer graphene functionalized through thermal 1,3-dipolar cycloadditions with imino esters: A versatile platform for supported ligands in catalysis
-
Multilayer graphene (MLG), obtained by mild sonication of graphite in NMP or pyridine, was fully characterized via atomic force microscopy (AFM), transmission electron microscopy (TEM), Raman spectroscopy and X-ray photoemission spectroscopy (XPS). Then, it was functionalized via 1,3-dipolar cycloaddition with azomethine ylides generated by thermal 1,2-prototropy of various imino esters. The resulting MLG, containing substituted proline-based amine functions, was characterized by XPS and it showed high nitrogen loading, ranging from 0.6 to 4.2 at% depending on the imino ester used. Among these functionalized MLGs a probe sample was subjected to ester hydrolysis and used as a heterogeneous N,O-chelating ligand to coordinate iridium atomic centers. This supported complex was also characterized by XPS and its catalytic activity was tested in the hydrogen transfer reduction of acetophenone, obtaining up to 85% yield. Furthermore, this catalyst could be recycled up to four times.
- Ferrándiz-Saperas, Marcos,Ghisolfi, Alessio,Cazorla-Amorós, Diego,Nájera, Carmen,Sansano, José M.
-
supporting information
p. 7462 - 7465
(2019/07/04)
-
- Switching Diastereoselectivity in Catalytic Enantioselective (3+2) Cycloadditions of Azomethine Ylides Promoted by Metal Salts and Privileged Segphos-Derived Ligands
-
Catalytic enantioselective 1,3-dipolar cycloaddition between imino esters and electrophilic alkenes, employing chiral metal complexes derived from copper(I) and silver(I) salts and (S)-DM-or (S)-DTBM-Segphos as ligands produces diastereodivergently exo-or
- Caleffi, Guilherme S.,Larran?ga, Olatz,Ferrándiz-Saperas, Marcos,Costa, Paulo R. R.,Nájera, Carmen,De Cózar, Abel,Cossió, Fernando P.,Sansano, José M.
-
p. 10593 - 10605
(2019/09/03)
-
- Ag/P-Stereogenic Phosphine-Catalyzed Enantioselective 1,3-Dipolar Cycloadditions: A Method to Optically Active Pyrrolidines
-
A Ag/P-stereogenic phosphine-complex-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with electron-deficient olefins is reported. In this reaction, highly functionalized pyrrolines with a spiro-quaternary stereogenic center were obtained in good yields (up to 99%) with excellent levels of diastereo-(up to >20:1 dr) and enantioselectivities (up to >99% ee). The chirality of adducts was controlled predominantly by the P-stereogenic phosphines.
- Zhi, Mengna,Gan, Zhenjie,Ma, Rong,Cui, Hao,Li, Er-Qing,Duan, Zheng,Mathey, Fran?ois
-
supporting information
(2019/05/07)
-
- Facile synthesis of chiral [2,3]-fused hydrobenzofuran: Via asymmetric Cu(i)-catalyzed dearomative 1,3-dipolar cycloaddition
-
Intermolecular asymmetric dearomative 1,3-dipolar cycloaddition of 2-nitrobenzofurans with azomethine ylides was enabled by using a chiral Cu(i)/(S,Sp)-iPr-Phosferrox catalyst. As a result, a series of highly stereoselective chiral [2,3]-fused hydrobenzofurans possessing four contiguous stereogenic centers were obtained with good to high yields, diastereoselectivities and enantioselectivities. The reaction has broad substrate scope tolerating various functional groups.
- Liang, Lei,Niu, Hong-Ying,Wang, Dong-Chao,Yang, Xin-He,Qu, Gui-Rong,Guo, Hai-Ming
-
supporting information
p. 553 - 556
(2019/01/10)
-
- Well-Designed Phosphine-Urea Ligand for Highly Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition of Methacrylonitrile: A Combined Experimental and Theoretical Study
-
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.
- 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)
-
- Application of the Cu(i)/TEMPO/O2 catalytic system for aerobic oxidative dehydrogenative aromatization of pyrrolidines
-
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.
- Luo, Zheng,Liu, Yan,Wang, Chao,Fang, Danjun,Zhou, Junyu,Hu, Huayou
-
supporting information
p. 4609 - 4613
(2019/09/09)
-
- Enantioselective Mannich Reaction of Glycine Iminoesters with N-Phosphinoyl Imines: A Bifunctional Approach
-
A bifunctional catalytic approach for the asymmetric Mannich reaction of glycine iminoesters with N-phosphinoyl imines has been developed. By the combination of metal catalysis and organocatalysis, the vicinal two stereogenic centers were efficiently constructed, affording a wide range of syn-diamino esters in high yields with excellent enantio- and diastereoselectivities (up to >99:1 dr, 99% ee).
- Zhang, Changhui,Yang, Jiao,Zhou, Wenqiang,Tan, Qiuyuan,Yang, Zhao,He, Ling,Zhang, Min
-
supporting information
p. 8620 - 8624
(2019/11/03)
-
- Substituted Pyrrolidines and Methods of Use
-
The invention discloses compounds of Formula (I) wherein R1, R2, R2A, R3, R3A, R4, R4A, and R5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.
- -
-
Paragraph 2166
(2018/04/20)
-
- Ligand-Controlled Inversion of Diastereo- and Enantioselectivity in Silver-Catalyzed Azomethine Ylide-Imine Cycloaddition of Glycine Aldimino Esters with Imines
-
A highly diastereo- and enantioselective silver-catalyzed azomethine ylide-imine (AYI) cycloaddition reaction of glycine aldimino esters with imines was developed in which the Xing-Phos-controlled syn-selective or DTBM-Segphos-induced anti-selective AYI cycloaddition reaction could be applied to the synthesis of a variety of stereodivergent 1-alkyl-2,5-substituted imidazolidines with high yields and excellent enantioselectivities (up to 99% ee) as well as good diastereoselectivities (up to 99:1 dr) under mild reaction conditions.
- Yu, Bo,Yang, Ke-Fang,Bai, Xing-Feng,Cao, Jian,Zheng, Zhan-Jiang,Cui, Yu-Ming,Xu, Zheng,Li, Li,Xu, Li-Wen
-
supporting information
p. 2551 - 2554
(2018/05/17)
-
- A biphenyl alanine derivative preparation method
-
The invention relates to a preparation method of a compound represented by the formula (i); and the compound represented by the formula (i) is prepared by taking glycine methyl ester or hydrochloride thereof as the starting material through benzaldehyde protection, benzyl chloride biphenyl alkylation and deprotection. According to the invention, the starting material is easy to obtain and low in cost; furthermore, an intermediate related in the reaction process is unnecessary to separate and purify; the preparation method is simple to operate and moderate in reaction condition; and therefore, the preparation method is applied to industrialized mass production.
- -
-
Paragraph 0023-0024; 0042; 0045; 0048; 0051; 0054; 0062-0063
(2018/05/24)
-
- Tandem nucleophilic addition-cycloaddition of arynes with α-iminoesters: Two concurrent pathways to imidazolidines
-
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.
- Jia, Hao,Guo, Zhenyan,Liu, Honglei,Mao, Biming,Shi, Xueyan,Guo, Hongchao
-
supporting information
p. 7050 - 7053
(2018/07/05)
-
- Silicon-based Bulky Group?Tuned Parallel Kinetic Resolution in Copper-Catalyzed 1,3-Dipolar Additions
-
The development of new strategies or reaction processes that tease new reactivity of functional groups continues to spur synthetic chemists toward innovative solutions that access new compounds. Herein, we find that the silicon-based bulky group enables a 1,3-dipolar addition?initiated parallel kinetic resolution (PKR) to occur unexpectedly, leading to the highly enantioselective synthesis of two structurally different types of amino acid derivatives via chemodivergent [3+2] cycloaddition reactions and tandem conjugate addition-elimination reaction respectively. The resulting and structurally divergent enantioenriched amino acid derivatives that contain four contiguous stereogenic centers and an all-carbon quaternary center were obtained with up to 99% ee with >95:1 dr and good yields. (Figure presented.).
- Yuan, Yang,Zheng, Zhan-Jiang,Li, Li,Bai, Xing-Feng,Xu, Zheng,Cui, Yu-Ming,Cao, Jian,Yang, Ke-Fang,Xu, Li-Wen
-
supporting information
p. 3002 - 3008
(2018/04/30)
-
- Total synthesis and biological evaluation of spirotryprostatin A analogs
-
Based on the spirotryprostatin A structure, a series of compounds belonging to spiro-indolyl diketopiperazine structural class were designed and synthesized, which embody an oxindole with an all-carbon quaternary stereocenter. The total synthesis can efficiently be accessed in a seven-step reaction sequence with 18–28% overall yield from commercially available materials, and a highly enantioselective 1,3-dipolar cycloaddition, N-acylation of the resulting stereochemically complex spiro[pyrrolidin-3,3′-oxindole]s core with Fmoc-L-pro-Cl and spontaneous ring closure upon N-deprotection were obtained. The synthesized compounds 13a–e and 15a–e were evaluated for their antibacterial activities. The result showed that compounds 13b and 15b were active only against Gram-positive bacteria, and selective antibacterial activity was exhibited by compounds 13d and 13e against Streptococcus lactis. Further, all the remaining compounds showed a certain degree of antibacterial activity. In addition, the structure–activity relationship is also discussed.
- Ma, Yangmin,Fan, Chao,Jia, Bin,Cheng, Pei,Liu, Jia,Ma, Yuqiang,Qiao, Ke
-
p. 737 - 746
(2017/10/17)
-
- Synthesis of Pyrrole via a Silver-Catalyzed 1,3-Dipolar Cycloaddition/Oxidative Dehydrogenative Aromatization Tandem Reaction
-
Pyrroles are an important group of heterocyclic compounds with a wide range of interesting properties, which have resulted in numerous applications in a variety of fields. Despite the importance of these compounds, there have been few reports in the literature pertaining to the synthesis of pyrroles from simple alkenes using a one-pot sequential 1,3-dipolar cycloaddition/aromatization reaction sequence. Herein, we report the development of a benzoyl peroxide-mediated oxidative dehydrogenative aromatization reaction for the construction of pyrroles. We subsequently developed a one-pot tandem reaction that combined this new method with a well-defined silver-catalyzed 1,3-dipolar cycloaddition reaction, thereby providing a practical method for the synthesis of multisubstituted pyrroles from easy available alkenes. The mechanism of this oxidative dehydrogenative aromatization reaction was also examined in detail.
- Liu, Yan,Hu, Huayou,Wang, Xiang,Zhi, Sanjun,Kan, Yuhe,Wang, Chao
-
p. 4194 - 4202
(2017/04/28)
-
- 5 - azaspiro [2.4] heptane - 6 - carboxylic acid derivatives of the synthesis method (by machine translation)
-
The present invention provides a (5S) - 5 - azaspiro [2.4] heptane - 6 - carboxylic acid derivatives of the synthetic method, in order to 1, 1 - cyclopropane dicarboxylic alcohol as the starting material, the reaction with thionyl chloride, is oxidized and get sulfonic acid ester compound, then with glycine methyl ester imine under the action of the tertiary butyl alcohol potassium condensation, again through the system acidic, alkaline methylsulphonyl complete hydrolysis, cyclization, amino protection of the racemic product, finally split to obtain the finished product, the total yield up to 30% or more, the reaction route step is short, reagent used in the security, the operation is simple, of low cost, high yield, suitable for industrial production. (by machine translation)
- -
-
Paragraph 0051-0053
(2017/08/25)
-
- Ag2CO3/CA-AA-amidphos multifunctional catalysis in the enantioselective 1,3-dipolar cycloaddition of azomethine ylides
-
The new Ag2CO3/CA-AA-amidphos complexes have been demonstrated as highly efficient multifunctional catalysts in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides. Under optimal conditions, highly functionalized endo-4 pyrrolidines were obtained with excellent yields (up to 99% yield) and enantioselectivities (up to 96% ee).
- Wang, Haifei,Deng, Qifu,Zhou, Zhipeng,Hu, Shunqin,Liu, Zhiguo,Zhou, Li-Yi
-
supporting information
p. 404 - 407
(2016/02/18)
-
- Synthesis of Azacyclic Nucleoside Analogues via Asymmetric [3 + 2] Cycloaddition of 9-(2-Tosylvinyl)-9H -purines
-
With 9-(2-tosylvinyl)-9H-purines as the dipolarophiles, a series of chiral azacyclic nucleosides with four continuous stereocenters were obtained in 86-99% yields, >20:1 dr, and 94 → 99% ee via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition. Both (E)- and (Z)-9-(2-tosylvinyl)-9H-purines were suitable dipolarophiles, enriching the structure diversity of azacyclic nucleosides. Furthermore, when α-methyl imino ester was explored, the corresponding azacyclic nucleoside with a chiral quaternary stereocenter could also be afforded with excellent results. (Chemical Equation Presented).
- Zhang, Dan-Jie,Xie, Ming-Sheng,Qu, Gui-Rong,Gao, Yao-Wei,Guo, Hai-Ming
-
supporting information
p. 820 - 823
(2016/03/01)
-
- Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition
-
An efficient strategy has been established for the enantiodivergent synthesis of natural product inspired compounds embodying both tropane and pyrrolidine natural product fragments. This strategy includes the enantioselective kinetic resolution of racemic tropanes by means of a copper(I)-catalyzed [3+2] cycloaddition and allows the preparation of two enantiopure products in a one-pot reaction in high yield and with high diastereo- and enantioselectivity by using one chiral catalyst.
- Xu, Hao,Golz, Christopher,Strohmann, Carsten,Antonchick, Andrey P.,Waldmann, Herbert
-
supporting information
p. 7761 - 7765
(2016/07/07)
-
- Enantiodivergent Synthesis of Bis-Spiropyrrolidines via Sequential Interrupted and Completed (3 + 2) Cycloadditions
-
Both (5R)- and (5S)-1,7-diazaspiro[4.4]nonan-6-ones are obtained via a sequence of interrupted and completed stepwise (3 + 2) cycloadditions between azomethine ylides and π-deficient alkenes. The only source of chirality along the whole process is an enantiopure ferrocenyl pyrrolidine catalytic ligand. When the starting imine incorporates two aryl groups or one aryl group with one electron-releasing substituent, the reaction between the azomethine ylide and the alkene stops at the first step, leading to the corresponding Michael adduct. When imines derived from p-methoxybenzaldehyde are used, the corresponding syn-α-amino-γ-nitro ester is obtained with almost complete enantiocontrol. In contrast, imines derived from benzophenone lead to the corresponding anti analogue. From this interrupted (3 + 2) cycloaddition, cis- and trans-α-amino-γ-lactams can be obtained via hydrogenation of the nitro group followed by in situ cyclization. Imines derived from these latter compounds are the precursors of N-metalated azomethine ylides from which up to four new chiral centers can be generated via completed (3 + 2) cycloaddition reactions with full regio- and diastereocontrol. Cis- and trans-γ-lactams lead to opposite bis-spiropyrrolidine enantiomers. Therefore, both enantiomeric series of spiro compounds can be obtained by means of the same catalytic system. The potential of these rigid, densely substituted homochiral compounds in medicinal chemistry is briefly described.
- Conde, Egoitz,Rivilla, Iván,Larumbe, Amaia,Cossío, Fernando P.
-
p. 11755 - 11767
(2015/12/11)
-
- Cycloaddition reactions of glycine imine anions to phenylazocarboxylic esters - A new access to 1,3,5-trisubstituted 1,2,4-triazoles
-
Phenylazocarboxylic tert-butyl esters have recently been shown to be highly versatile building blocks due to their ability to undergo nucleophilic aromatic substitutions under mild conditions, particularly well with [18F]fluoride, and to act as precursors for aryl radicals. In this article, we now report first examples for cycloaddition reactions to phenylazocarboxylates. In a one-pot reaction with readily accessible glycine imines, a variety of highly substituted 1,2,4-triazoles could be obtained.
- Lasch, Roman,Heinrich, Markus R.
-
p. 4282 - 4295
(2015/06/08)
-
- Structural modulation of silver complexes and their distinctive catalytic properties
-
A family of silver(i) complexes, [Ag2(L)2(OOCCF 3)2] (1), [Ag(L)0.5(OOCCF3)] (2), [Ag(L)2](OOCCF3)(H2O)2 (3), was obtained by reactions of 4,4′-di(2-oxazolinyl)biphenyl (L) and AgOOCCF3 in different reaction media. Compound 1 has a 1D chain structure with alternative connections between the Ag(i) and L ligand. When the crystal nucleation inductor, pyrazine, was added into the reaction system, complex 2 was isolated with no pyrazine observed in its structure. In 2, the 1D inorganic chains formed by Ag(i) cations and OOCCF3- anions were connected by the L ligand to produce a 2D network. When a different inductor, imidazole, was added into the reaction system, 3 with (4,4) topology was synthesized, and again no imidazole was found in 3. When 1-3 were used as catalysts for cycloaddition reactions between imino esters and methyl acrylate, 3 affords the highest yield, in which the particular size of the channels in 3 led to its selective catalytic performance.
- Zhao, Yue,Chen, Kai,Fan, Jian,Okamura, Taka-Aki,Lu, Yi,Luo, Li,Sun, Wei-Yin
-
p. 2252 - 2258
(2014/01/17)
-
- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
-
The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
- -
-
Paragraph 0301-0302
(2014/08/19)
-
- A rapid and divergent access to chiral azacyclic nucleoside analogues via highly enantioselective 1,3-dipolar cycloaddition of β-nucleobase substituted acrylates
-
A rapid and divergent access to chiral azacyclic nucleoside analogues has been established via highly exo-selective and enantioselective 1,3-dipolar cycloaddition of azomethine ylides with β-nucleobase substituted acrylates. Using 1 mol% of a chiral copper complex, various chiral azacyclic nucleoside analogues were obtained in high yields, excellent exo-selectivities and enantioselectivities (98 to >99% ee). This journal is
- Yang, Qi-Liang,Xie, Ming-Sheng,Xia, Chao,Sun, Huan-Li,Zhang, Dan-Jie,Huang, Ke-Xin,Guo, Zhen,Qu, Gui-Rong,Guo, Hai-Ming
-
supporting information
p. 14809 - 14812
(2014/12/11)
-
- Enantioselective synthesis of 4-aminopyrrolidine-2,4-dicarboxylate derivatives via Ag-catalyzed cycloaddition of azomethine ylides with alkylidene azlactones
-
A catalytic highly enantioselective silver-DTBM-segphos catalyzed cycloaddition of α-iminoesters with alkylidene azlactones is reported. This procedure provides an effective access to 4-aminopyrrolidine-2,4- dicarboxylate derivatives with high diastereo- and enantioselectivity. The Royal Society of Chemistry 2013.
- Gonzalez-Esguevillas, Maria,Adrio, Javier,Carretero, Juan C.
-
supporting information
p. 4649 - 4651
(2013/06/05)
-
- Design, synthesis, and functional evaluation of leukocyte function associated antigen-1 antagonists in early and late stages of cancer development
-
The integrin leukocyte function associated antigen 1 (LFA-1) binds the intercellular adhesion molecule 1 (ICAM-1) by its αL-chain inserted domain (I-domain). This interaction plays a key role in cancer and other diseases. We report the structure-based design, small-scale synthesis, and biological activity evaluation of a novel family of LFA-1 antagonists. The design led to the synthesis of a family of highly substituted homochiral pyrrolidines with antiproliferative and antimetastatic activity in a murine model of colon carcinoma, as well as potent antiadhesive properties in several cancer cell lines in the low micromolar range. NMR analysis of their binding to the isolated I-domain shows that they bind to the I-domain allosteric site (IDAS), the binding site of other allosteric LFA-1 inhibitors. These results provide evidence of the potential therapeutic value of a new set of LFA-1 inhibitors, whose further development is facilitated by a synthetic strategy that is versatile and fully stereocontrolled.
- San Sebastián, Eider,Zimmerman, Tahl,Zubia, Aizpea,Vara, Yosu,Martin, Elyette,Sirockin, Finton,Dejaegere, Annick,Stote, Roland H.,Lopez, Xabier,Pantoja-Uceda, David,Valcárcel, María,Mendoza, Lorea,Vidal-Vanaclocha, Fernando,Cossío, Fernando P.,Blanco, Francisco J.
-
p. 735 - 747
(2013/03/28)
-
- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
-
The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter-and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
- -
-
Paragraph 00211
(2013/06/05)
-
- Discovery of inhibitors of the wnt and hedgehog signaling pathways through the catalytic enantioselective synthesis of an iridoid-inspired compound collection
-
Cousins you can count on: An iridoid-inspired compound collection was synthesized efficiently by the resolution of cyclic enones in an asymmetric cycloaddition with azomethine ylides. The collection contained novel potent inhibitors of the Wnt and Hedgehog signaling pathways. Copyright
- Takayama, Hiroshi,Jia, Zhi-Jun,Kremer, Lea,Bauer, Jonathan O.,Strohmann, Carsten,Ziegler, Slava,Antonchick, Andrey P.,Waldmann, Herbert
-
supporting information
p. 12404 - 12408
(2013/12/04)
-
- Asymmetric [3+2] cycloaddition of azomethine ylides catalyzed by silver(I) triflate with a chiral bipyrrolidine-derived phosphine ligand
-
Two novel chiral bipyrrolidine-derived phosphine ligands L1 and L2 were synthesized. The AgOTf + L1 protocol catalyzes the asymmetric [3+2] cycloaddition of azomethine ylides with alkenes to give highly substituted pyrrolidines in good yields (up to 90%) with moderate to high diastereoselectivities (up to >19:1 dr) and enantioselectivities (up to 76%).
- Gu, Xin,Xu, Zhen-Jiang,Che, Chi-Ming,Lo, Vanessa Kar-Yan
-
p. 3307 - 3314,8
(2012/12/12)
-
- Asymmetric [3+2] cycloaddition of azomethine ylides catalyzed by silver(I) triflate with a chiral bipyrrolidine-derived phosphine ligand
-
Two novel chiral bipyrrolidine-derived phosphine ligands L1 and L2 were synthesized. The AgOTf + L1 protocol catalyzes the asymmetric [3+2] cycloaddition of azomethine ylides with alkenes to give highly substituted pyrrolidines in good yields (up to 90%) with moderate to high diastereoselectivities (up to >19:1 dr) and enantioselectivities (up to 76%). Georg Thieme Verlag Stuttgart.New York.
- Gu, Xin,Xu, Zhen-Jiang,Lo, Vanessa Kar-Yan,Che, Chi-Ming
-
p. 3307 - 3314
(2013/01/15)
-
- Silver-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with β-boryl acrylates
-
The Ag-catalyzed 1,3-dipolar cycloaddition of (?)-β-borylacrylates with azomethine ylides is described. The resulting 3-borylpyrrolidine derivatives were obtained in high yields and complete endo selectivities using AgOAc/ dppe as catalyst system and B(dam) as boryl group. Transformation of the B(dam) group into pinacol borane and oxidation afforded 3-hydroxyproline derivatives in high yields.
- Lopez-Perez, Ana,Segler, Marwin,Adrio, Javier,Carretero, Juan C.
-
supporting information; experimental part
p. 1945 - 1948
(2011/06/20)
-
- Asymmetric construction of 3-vinylidene-pyrrolidine derivatives containing allene moiety via Ag(i)/TF-BiphamPhos-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with diethyl 2-(3,3-diphenylpropa-1,2-dienylidene) malonate
-
Catalytic asymmetric 1,3-dipolar cycloaddition of various azomethine ylides with diethyl 2-(3,3-diphenylpropa-1,2-dienylidene)malonate has been developed successfully with good to excellent enantioselectivity for the effcient construction of 3-vinylidene-pyrrolidine derivatives containing a unique allene moiety.
- Xue, Zhi-Yong,Fang, Xin,Wang, Chun-Jiang
-
supporting information; experimental part
p. 3622 - 3624
(2011/06/17)
-
- Metal-free asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides catalyzed by chiral tertiary amine thiourea
-
The first metal-free asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides catalyzed by chiral tertiary amine thiourea to form multiply substituted pyrrolidines in excellent yields (up to 89%) and enantioselectivities (up to 96% ee) is presented. This procedure allows a rapid diversity-oriented synthesis of chiral pyrrolidine derivatives with high optical purity. A series of bifunctional thiourea catalysts were applied for the first time to the highly asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides togive the products in excellent yields (up to 89%) and enantioselectivities (up to 96% ee).
- Bai, Jian-Fei,Wang, Liang-Liang,Peng, Lin,Guo, Yun-Long,Ming, Jun-Nan,Wang, Fei-Ying,Xu, Xiao-Ying,Wang, Li-Xin
-
experimental part
p. 4472 - 4478
(2011/10/01)
-
- Sc(OTf)3-catalyzed tandem [3+2] cycloaddition/nucleophilic ring-opening reaction of cyclopropane 1,1-diesters with azomethine ylides
-
A new Sc(OTf)3-catalyzed tandem reaction combined with a dimerized self-[3+2] cycloaddition of azomethine ylide and a nucleophilic ring-opening of cyclopropane 1,1-diester has been developed. A series of polyfunctionalized imidazolidine derivatives were synthesized by this reaction (Yield 44-77 %). In some cases, this tandem reaction was also accompanied by a cross-[3+2] cycloaddition of cyclopropane 1,1-diester with imine.
- Fang,Hu,Ren,Wang
-
experimental part
p. 1479 - 1487
(2011/12/22)
-
- Design of small-molecule thrombin inhibitors based on the cis-5-phenylproline scaffold
-
The design of novel organic compounds containing no strongly basic amidine or guanidine functional groups typical of serine protease inhibitors was performed to develop an oral anticoagulant drug. A three-dimensional computational model for thrombin active site was constructed and optimized for docking of small-molecule organic compounds and calculating the energies of inhibitor-enzyme interactions. Novel racemic derivatives of 1-[2-(4- chlorophenylthio)acetyl]-5-phenylpyrrolidine-2,4-dicarboxylic acids were synthesized for which Cl-π interactions between the inhibitors and the S1 pocket of thrombin active site are predicted by modeling. The compounds synthesized deactivate thrombin in vitro and the inhibition properties show good correlations with the results of calculations.
- Kudryavtsev,Shulga,Chupakhin,Churakov,Datsuk,Zabolotnev,Zefirov
-
scheme or table
p. 685 - 693
(2012/02/05)
-
- Cu-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-phenylsulfonyl enones. Ligand controlled diastereoselectivity reversal
-
(Chemical Equation Presented) A catalytic asymmetric procedure for the 1,3-dipolar cycloaddition of (E)-β-phenylsulfonyl enones with azomethine ylides to provide highly functionalized pyrrolidine derivatives is described. In the presence of chiral CuI-Segphos catalysts the aducts were obtained with high regio-, diastereo-, and enantioselectivity. Interestingly, a switch from endo to exo selectivity was observed when Segphos or DTBM-Segphos ligand was used.
- Robles-Machin, Rocio,Gonzalez-Esguevillas, Maria,Adrio, Javier,Carretero, Juan C.
-
supporting information; experimental part
p. 233 - 236
(2010/04/06)
-
- Pyrrole and oligopyrrole synthesis by 1,3-dipolar cycloaddition of azomethine ylides with sulfonyl dipolarophiles
-
A procedure for the synthesis of functionalized, substituted pyrroles by 1,3-dipolar cycloaddition of azomethine ylides has been developed. This protocol is based on the metal-catalyzed cycloaddition of α-iminoesters with sulfonyl dipolarophiles, followed by the base-promoted elimination of the sulfonyl groups. A wide variety of 2,5-disubstituted and 2,3,5- and 2,4,5trisubstituted pyrroles have been prepared in satisfactory yields from 1,2bis(sulfonyl ethylene), ss-sulfonylenones, and ss- sulfonylacrylates. This method can be applied in an iterative and straightforward manner to the construction of oligopyrroles, from bipyrroles to pentapyrroles. Iterative [n+1] and [n+2] approaches have been devised, the latter involves double 1,3-dipolar cycloaddition from pyrrolylbased bis(iminoesters).
- Robles-Machin, Rocio,Lopez-Perez, Ana,Gonzalez-Esguevillas, Maria,Adrio, Javier,Carretero, Juan Carlos
-
supporting information; experimental part
p. 9864 - 9873
(2010/11/16)
-
- Carbenium ion trapping using sulfonamides: an acid-catalysed synthesis of pyrrolidines by intramolecular hydroamination
-
Cyclisations of homoallylic sulfonamides proceed smoothly via carbenium ion generation using trifluoromethanesulfonic (triflic) acid, the ease of cyclisation being directly related to the ion stability to give good to excellent yields of the corresponding pyrrolidines. Both toluene- and nitrophenyl-sulfonyl groups are suitable for all substrates tested whereas the corresponding carbamates are only useful in cases of tertiary and highly stabilised carbenium ions. Polyene-derived sulfonamides can also be cyclised to the corresponding polycyclic systems in remarkably high yields, in reactions reminiscent of related cascades encountered in terpene biosynthesis.
- Griffiths-Jones (née Haskins), Charlotte M.,Knight, David W.
-
experimental part
p. 4150 - 4166
(2010/07/05)
-
- Diversity oriented synthesis of pyrrolidines via natural carbohydrate solid acid catalyst
-
Natural carbohydrate scaffold catalyzed diastereoselective synthesis of functionalized pyrrolidines have been developed via 1,3-dipolar cycloaddition of azomethine ylides derived from α-imino esters with dienes or dipolarophiles. Naturally most abundant carbohydrates, like cellulose and starch, were converted into their sulfuric acid derivative, which are exhibiting efficient catalytic properties, along with excellent cost effectivity and recyclability. The advantages of this methodology are diversity oriented metal free synthesis of functionalized pyrrolidines, mild reaction condition, high diasteroselectivity and yield.
- Kumar, Atul,Gupta, Garima,Srivastava, Suman
-
experimental part
p. 458 - 462
(2010/09/05)
-
- The phenylsulfonyl group as a temporal regiochemical controller in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides
-
(Chemical Equation Presented) Controlling the regioselectivity: The phenylsulfonyl group controlled the regioselectivity in the title reaction to afford pyrrolidine-2,3-dicarboxylates with good regioselectivity and high exo selectivity and enantioselectivity (see scheme). The products are precursors to substituted pyrrolidines and pyrrolines that are not attainable by direct 1,3-dipolar cycloadditions with typical acrylates.
- Lopez-Perez, Ana,Adrio, Javier,Carretero, Juan C.
-
supporting information; experimental part
p. 340 - 343
(2009/04/14)
-
- Probing of the cis-5-phenyl proline scaffold as a platform for the synthesis of mechanism-based inhibitors of the Staphylococcus aureus sortase SrtA isoform
-
cis-5-Phenyl prolinates with electrophilic substituents at the fourth position of a pyrrolidine ring were synthesized by 1,3-dipolar cycloaddition of arylimino esters with divinyl sulfone and acrylonitrile. 4-Vinylsulfonyl 5-phenyl prolinates inhibit Staphylococcus aureus sortase SrtA irreversibly by modification of the enzyme Cys184 and could be used as hits for the development of antibacterials and antivirulence agents.
- Kudryavtsev, Konstantin V.,Bentley, Matthew L.,McCafferty, Dewey G.
-
body text
p. 2886 - 2893
(2009/09/05)
-