- Rational modification of Mannich base-type derivatives as novel antichagasic compounds: Synthesis, in vitro and in vivo evaluation
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The current chemotherapy against Chagas disease is inadequate and insufficient. A series of ten Mannich base-type derivatives have been synthesized to evaluate their in vitro antichagasic activity. After a preliminary screening, compounds 7 and 9 were sub
- Paucar, Rocío,Martín-Escolano, Rubén,Moreno-Viguri, Elsa,Azqueta,Cirauqui,Marín, Clotilde,Sánchez-Moreno, Manuel,Pérez-Silanes, Silvia
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- Substituent Effects on the Photosolvolyses of 2-Chloropropiophenones in 2,2,2-Trifluoroethanol
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The substituent effects on the product distribution of the photosolvolyses of 2-chloropropiophenones in 2,2,2-trifluoroethanol were investigated.A ?-electron-donating methoxy substituent at p- and m-position enhanced the heterolytic product of the nucleophilic substitution over that of phenyl-rearrangement.
- Usui, Satoshi,Nishimoto, Jyunji,Ohkubo, Katsutoshi
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- Rongalite as C1 Synthon and Sulfone Source: A Practical Sulfonylmethylation Based on the Separate-Embedding Strategy
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Rongalite has been used in several challenging synthetic transformations with operationally simple and effective protocols. However, the employment of multiple characteristics of rongalite in synthetic chemistry is comparatively little known. Herein we report a separate-embedding type sulfonylmethylation of sulfoxonium ylides in which rongalite concurrently acted as a sulfone source, C1 synthon, radical initiator, and potential reducing reagent for the first time. Notably, this facile and easy-handling reaction does not require a catalyst or prefunctionalized sulfonylmethylation reagents.
- Chen, Xiang-Long,Wu, Chun-Yan,Ma, Jin-Tian,Zhuang, Shi-Yi,Yu, Zhi-Cheng,Wu, Yan-Dong,Wu, An-Xin
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supporting information
p. 223 - 227
(2022/01/04)
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- Nickel-Catalyzed C(sp3)-H Functionalization of Benzyl Nitriles: Direct Michael Addition to Terminal Vinyl Ketones
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An efficient nickel(0)-catalyzed addition of benzyl nitriles to terminal vinyl ketones via C(sp3)-H functionalization has been developed. The reaction provides a novel and efficient protocol for the synthesis of α-functionalized benzyl nitriles with a wide range of structural diversity under mild reaction conditions while obviating the use of a strong base. The work might be potentially useful toward the development of an enantioselective variant using chiral nitrogen ligands.
- Zhang, Ninghui,Zhang, Chunli,Hu, Xiaoping,Xie, Xin,Liu, Yuanhong
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supporting information
p. 6004 - 6009
(2021/07/31)
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- Generation of α-Boryl Radicals and Their Conjugate Addition to Enones: Transition-Metal-Free Alkylation of gem-Diborylalkanes
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A transition-metal-free method for the alkylation of gem-diborylalkanes with α,β-unsaturated ketones has been developed. It is demonstrated that the α-boryl radicals can be generated efficiently from gem-diborylalkanes with the aid of catechol and oxidants. The α-boryl radicals formed through such process can be engaged in conjugate addition reaction with α,β-unsaturated ketones. This transformation is a straightforward method for the synthesis of γ-borylketones.
- Wu, Chaoqiang,Bao, Zhicheng,Dou, Bowen,Wang, Jianbo
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supporting information
p. 2294 - 2298
(2021/01/18)
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- Enantioselective Copper-Catalyzed Electrophilic Sulfenylation of Cyclic Imino Esters
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Herein we report an enantioselective sulfenylation of cyclic imino esters with the efficient and versatile sulfenylation reagent S-alkyl 4-methylbenzenesulfonothioates. By utilizing the Cu/tBu-Phosferrox catalytic system, we can assemble diverse S-alkyl groups into the cyclic imino esters under mild conditions in good yields and with excellent enantioselectivities. Remarkably, this method demonstrates a high tolerance of diverse functional groups and proves to be applicable in the late-stage functionalization of pharmaceuticals.
- Chen, Zhiwei,Lin, Huaxin,Han, Jian,Fang, Dongmei,Wang, Min,Liao, Jian
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supporting information
p. 9146 - 9150
(2021/11/30)
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- Metabolically stable vanillin derivatives for the treatment of hypoxia
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Vanillin derivative compounds that bind covalently with hemoglobin are provided. Methods of treating sickle cell disease and other hypoxia-related disorders by administering such compounds are also provided.
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- Design and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease
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The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. The only treatments currently available are nitro-derivative drugs that are characterised by high toxicity and limited efficacy. Therefore, there is an urgent need for more effective, less toxic therapeutic agents. We have previously identified the potential for Mannich base derivatives as novel inhibitors of this parasite. To further explore this family of compounds, we synthesised a panel of 69 new analogues, based on multi-parametric structure-activity relationships, which allowed optimization of both anti-parasitic activity, physicochemical parameters and ADME properties. Additionally, we optimized our in vitro screening approaches against all three developmental forms of the parasite, allowing us to discard the least effective and trypanostatic derivatives at an early stage. We ultimately identified derivative 3c, which demonstrated excellent trypanocidal properties, and a synergistic mode of action against trypomastigotes in combination with the reference drug benznidazole. Both its druggability and low-cost production make this derivative a promising candidate for the preclinical, in vivo assays of the Chagas disease drug-discovery pipeline.
- Atherton, Richard L.,Kelly, John M.,Olmo, Francisco,Sanz-Serrano, Julen,Alcolea, Verónica,Beltran-Hortelano, Iván,Pérez-Silanes, Silvia,Rubio-Hernández, Mercedes
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- Mild Darzens Annulations for the Assembly of Trifluoromethylthiolated (SCF3) Aziridine and Cyclopropane Structures
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We report mild new annulation approaches to trisubstituted trifluoromethylthiolated (SCF3) aziridines and cyclopropanes via Darzens inspired protocols. The products of these anionic annulations, rarely studied previously, possess attractive features rendering them valuable building blocks for synthesis platforms. In this study, trisubstituted acetophenone nucleophiles bearing SCF3 and bromine substituents in their α position were shown to undergo [2 + 1] annulations with vinyl ketones and tosyl-protected imines under mild reaction conditions.
- Delost, Michael D.,Njardarson, Jon T.
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supporting information
p. 6121 - 6125
(2021/08/16)
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- An investigation of structure‐activity relationships of azolylacryloyl derivatives yielded potent and long‐acting hemoglobin modulators for reversing erythrocyte sickling
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Aromatic aldehydes that bind to sickle hemoglobin (HbS) to increase the protein oxygen affinity and/or directly inhibit HbS polymer formation to prevent the pathological hypoxia‐induced HbS polymerization and the subsequent erythrocyte sickling have for s
- Abdulmalik, Osheiza,El‐araby, Moustafa E.,Ghatge, Mohini S.,Muhammad, Yosra A.,Omar, Abdelsattar M.,Paredes, Steven D.,Safo, Martin K.
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- Utility of Organoboron Reagents in Arylation of Cyclopropanols via Chelated Pd(II) Catalysis: Chemoselective Access to β-Aryl Ketones
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Organoborane reagents were investigated as coupling partners to cyclopropanol-derived β-ketone enolates in the presence of a chelated Pd(II) catalyst. Efficient coupling of a range of electronically and sterically diverse cyclopropanols and aryl/alkenyl boronic derivatives (39 examples, 65-94% yield) could be achieved with the generation of synthetically important β-aryl ketone intermediates in a chemoselective fashion. This reactivity paradigm, which broadens the scope of aryl donor partners to homoenolates, allows open-flask conditions, water as a cosolvent, and preparation of halogen-bearing β-aryl ketones that are distinct from previous methods. This chelated Pd(II) catalysis appears to be different from the Pd(0) pathway, as evident from deuterium scrambling studies that could reveal differentiating protonolysis of an α-keto carbopalladium complex in the terminal step.
- Ilangovan, Andivelu,Ramar, Thangeswaran,Subbaiah, Murugaiah A. M.
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- PROCESS FOR THE DIRECT ALPHA-METHYLENATION OF KETONES
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The invention relates to a process for preparing an α-methylene ketone comprising the step of reacting a ketone with formaldehyde in the presence of a catalyst which is an organic compound comprising at least one acid function or the corresponding salt, ester or amide thereof and at least one amine function or the corresponding ammonium salt, or a zwitterion thereof.
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Page/Page column 16; 17
(2020/06/10)
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- Heck Reactions of Acrolein or Enones and Aryl Bromides – Synthesis of 3-Aryl Propenals or Propenones and Consecutive Application in Multicomponent Pyrazole Syntheses
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3-(Hetero)aryl propenals or propenones are efficiently prepared by a Heck reaction of (hetero)aryl bromides and acrolein or vinyl ketones using Beller's CataCXium Ptb ligand under Jeffery's and Fu's conditions. The formation of these three-carbon building blocks is embedded into consecutive three- and pseudo-four-component syntheses of 3-(hetero)aryl and 3,5-diarylpyrazoles with a broad substitution pattern in moderate to excellent yield.
- Stephan, Marvin,Panther, Jesco,Wilbert, Fabio,Ozog, Pauline,Müller, Thomas J. J.
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supporting information
p. 2086 - 2092
(2020/03/23)
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- Copper-Catalyzed Asymmetric Hydrosilylation of β-Nitroethyl Aryl Ketones
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A copper-catalyzed asymmetric hydrosilylation of β-nitroethyl aryl ketones has been disclosed, and the corresponding chiral alcohols could be obtained in high yields (up to 99% yield) and excellent enantioselectivities (up to 96% ee). Moreover, the reaction worked well on a gram scale with 0.3 mol % of ligand loading, indicating that our protocol has potential applications in the synthesis of important pharmaceuticals such as Tranylcypromine and Ticagrelor.
- Zeng, Weijun,Tan, Xuefeng,Yu, Yang,Chen, Gen-Qiang,Zhang, Xumu
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supporting information
p. 858 - 862
(2020/01/31)
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- Manganese-Catalyzed Ring-Opening Coupling Reactions of Cyclopropanols with Enones
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A manganese-catalyzed ring-opening coupling reaction of cyclopropanols with enones for the facile and efficient preparation of 1,6-diketones is described. A wide array of synthetically important 1,6-diketones bearing manifold functional groups are obtained with up to 93% yield. These reactions feature broad substrate scopes, environmentally benign conditions, inexpensive catalyst, and operational simplicity.
- Zhang, Yong-Hui,Zhang, Wen-Wei,Zhang, Ze-Yu,Zhao, Kai,Loh, Teck-Peng
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supporting information
p. 5101 - 5105
(2019/07/03)
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- Photocatalytic C(sp3)?H Activation towards α-methylenation of Ketones using MeOH as 1 C Source Steering Reagent
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Unprecedented direct access to terminal enones via α-methylenation of aryl ketones to form C=C bond is achieved under visible-light conditions using methanol as one carbon source substrate and solvent as well. The reaction involves Cu@g-C3N4-catalysed in situ oxidation of methanol into formaldehyde followed by dehydrative cross aldol type reaction. Various aryl ketones react efficiently with MeOH, producing α,β-unsaturated carbonyl compounds only in 4–8 h at room temperature in excellent yield (84–97%). Operational simplicity, wide substrate scope, ambient reaction conditions, visible-light photocatalysis and novel application of MeOH as methylene donor substrate are the salient features making the envisaged protocol mild, efficient and green alternative to the existing methods for synthesis of such fine chemicals. (Figure presented.).
- Verma, Fooleswar,Shukla, Prashant,Bhardiya, Smita R.,Singh, Manorama,Rai, Ankita,Rai, Vijai K.
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supporting information
(2019/02/05)
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- Enantioselective addition of selenosulfonates to α,β-unsaturated ketones
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An organo-catalyzed enantioselective addition of selenosulfonates to α,β-unsaturated ketones was developed for the first time. With a chiral squaramide as an efficient catalyst, the desired α-selenylated ketones were obtained in a good yields with high enantioselectivity up to 89% ee, and good results could be obtained on a gram scale. The products could also be efficiently transformed into useful building blocks with a propenylic stereocenter; the strategy presented in this study may find further applications in organic synthesis.
- Luo, Shilong,Zhang, Nan,Wang, Zhen,Yan, Hailong
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supporting information
p. 2893 - 2901
(2018/05/03)
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- Structural Modification of Natural Product Ganomycin i Leading to Discovery of a α-Glucosidase and HMG-CoA Reductase Dual Inhibitor Improving Obesity and Metabolic Dysfunction in Vivo
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It is a great challenge to develop drugs for treatment of metabolic syndrome. With ganomycin I as a leading compound, 14 meroterpene derivatives were synthesized and screened for their α-glucosidase and HMG-CoA reductase inhibitory activities. As a result, a α-glucosidase and HMG-CoA reductase dual inhibitor ((R,E)-5-(4-(tert-butyl)phenyl)-3-(4,8-dimethylnona-3,7-dien-1-yl)furan-2(5H)-one, 7d) with improved chemical stability and long-term safety was obtained. Compound 7d showed multiple and strong in vivo efficacies in reducing weight gain, lowering HbAlc level, and improving insulin resistance and lipid dysfunction in both ob/ob and diet-induced obesity (DIO) mice models. Compound 7d was also found to reduce hepatic steatosis in ob/ob model. 16S rRNA gene sequencing, SCFA, and intestinal mucosal barrier function analysis indicated that gut microbiota plays a central and causative role in mediating the multiple efficacies of 7d. Our results demonstrate that 7d is a promising drug candidate for metabolic syndrome.
- Wang, Kai,Bao, Li,Zhou, Nan,Zhang, Jinjin,Liao, Mingfang,Zheng, Zhongyong,Wang, Yujing,Liu, Chang,Wang, Jun,Wang, Lifeng,Wang, Wenzhao,Liu, Shuangjiang,Liu, Hongwei
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p. 3609 - 3625
(2018/05/01)
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- Catalytic Cyclopropanol Ring Opening for Divergent Syntheses of γ-Butyrolactones and δ-Ketoesters Containing All-Carbon Quaternary Centers
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Catalytic ring opening cross coupling reactions of strained cyclopropanols have been useful for the syntheses of various β-substituted carbonyl products. Among these ring opening cross coupling reactions, the formation of α,β-unsaturated enone byproducts often competes with the desired cross coupling processes and has been a challenging synthetic problem to be addressed. Herein, we describe our efforts in developing divergent syntheses of a wide range of γ-butyrolactones and δ-ketoesters containing all-carbon quaternary centers via copper-catalyzed cyclopropanol ring opening cross couplings with 2-bromo-2,2-dialkyl esters. Our mechanistic studies reveal that unlike the previously reported cases, the formation of α,β-unsaturated enone intermediates is actually essential for the γ-butyrolactone synthesis and also contributes to the formation of the δ-ketoester product. The γ-butyrolactone synthesis is proposed to go through an intermolecular radical conjugate addition to the in situ generated α,β-unsaturated enone followed by an intramolecular radical cyclization to the ester carbonyl double bond. The reactions are effective to build all-carbon quaternary centers and have broad substrate scope.
- Ye, Zhishi,Cai, Xinpei,Li, Jiawei,Dai, Mingji
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p. 5907 - 5914
(2018/05/24)
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- Regioselective C?H Alkylation via Carboxylate-Directed Hydroarylation in Water
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In the presence of catalytic [RuCl2(p-cym)]2 and using Li3PO4 as the base, benzoic acids react with olefins in water to afford the corresponding 2-alkylbenzoic acids in moderate to excellent yields. This C?H alkylation process is generally applicable to diversely substituted electron-rich and electron-deficient benzoic acids, along with α,β-unsaturated olefins including unprotected acrylic acid. The widely available carboxylate directing group can be removed or utilized for further derivatization. Mechanistic investigations revealed that the transformation proceeds via a ruthenacycle intermediate.
- Zhang, Guodong,Jia, Fan,Goo?en, Lukas J.
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supporting information
p. 4537 - 4541
(2018/03/21)
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- Probing the mechanism of thermally driven thiol-Michael dynamic covalent chemistry
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The kinetics and mechanism of the thermally activated dynamic covalent exchange of thiol-Michael adducts is investigated. A model system of thiol-Michael adducts between thiophenol and phenylvinylketone derivatives and adducts between 2-mercaptoethanol phenylvinylketone derivatives in N,N-dimethylformamide (DMF) at elevated temperatures is used to probe the underlying exchange mechanism. The kinetic data show negligible free Michael acceptor, which is consistent with the highly efficient thiol-Michael reaction being a "click"-like reaction that significantly favors the adduct form. At elevated temperatures of 90 °C in DMF the thiol-Michael adducts reach equilibrium after 24 h, although equilibration did not occur within 24 h at 60 °C or 75 °C, and negligible exchange occurs under ambient conditions. A kinetic model was developed to describe the dynamic covalent exchange and equilibration. The experimental and simulation kinetic data of dynamic covalent exchange are consistent with the thiol-Michael adducts undergoing a retro-Michael reaction, followed by subsequent addition of a free thiol to the liberated Michael acceptor. Kinetic analysis is consistent with the fragmentation, or retro-Michael reaction, being the rate-determining step in the dynamic covalent exchange. This suggests that the key step in dynamic covalent exchange is not enhanced by addition of free thiol or free Michael acceptor, since the addition reaction is much faster than the retro-Michael reaction. This fundamental study will guide the design of organic compounds, materials, and bioconjugates that utilize the thermally activated dynamic covalent thiol-Michael linkages.
- Zhang, Borui,Chakma, Progyateg,Shulman, Max P.,Ke, Jun,Digby, Zachary A.,Konkolewicz, Dominik
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p. 2725 - 2734
(2018/04/26)
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- Stereoselective Allylic Alkylation of 1-Pyrroline-5-carboxylic Esters via a Pd/Cu Dual Catalysis
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The asymmetric allylation of 1-pyrroline-5-carboxylic esters has been accomplished through a synergistic Pd/Cu catalyst system under mild reaction conditions. The mechanistic studies suggested that (1) nucleophilic attack is the enantiodiscriminating step; (2) the cooperative action of two chiral reactive species, N-metalated azomethine ylides and ?€-allylpalladium, is most likely responsible for its high reactivity and excellent enantioselectivity (up to >99% ee); and (3) the steric hindrance and electronic factors of the allylic electrophiles and imino ester substrates are crucial for the formation of the linear products. A series of 3,4-2H-pyrrole derivatives bearing a quaternary stereogenic center were easily synthesized in high yields and with high to excellent regioselectivity and enantioselectivity.
- Liu, Penglin,Huo, Xiaohong,Li, Bowen,He, Rui,Zhang, Jiacheng,Wang, Tianhong,Xie, Fang,Zhang, Wanbin
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supporting information
p. 6564 - 6568
(2018/10/20)
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- Simple organocatalysts in multi-step reactions: An efficient one-pot Morita-Baylis-Hillman-type α-hydroxymethylation of vinyl ketones followed by the convenient, temperature-controlled one-pot etherification using alcohols
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1,4-Diazabicyclo[2.2.2]octane (DABCO) was utilized as versatile catalyst in a one-pot synthesis: First, for the preparation of alcoholic formaldehyde solutions from para-formaldehyde catalysed by using low loadings of inexpensive DABCO. Second, for the fast α-hydroxymethylation of alkylic and aromatic vinyl ketones in high yields. In a third step, the same catalyst can be used for an optional, temperature controlled in situ etherification of the Morita-Baylis-Hillman product with various alcohols on a multi-gram scale in moderate to good overall yields and high purities. Furthermore, an application of the ether in the enantioselective synthesis of a common building block for total synthesis is shown, thus providing a gram-scale access from inexpensive bulk chemicals.
- Mantel, Marvin,Guder, Marian,Pietruszka, J?rg
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supporting information
p. 5442 - 5450
(2018/05/25)
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- Cyanomethyl anion transfer reagents for diastereoselective Corey-Chaykovsky cyclopropanation reactions
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A readily available and bench-stable cyanomethyl sulfonium salt was used in highly diastereoselective Corey-Chaykovsky cyclopropanation reactions of electron-poor olefins. This efficient method provides a rapid route to access densely functionalized cyclopropyl nitriles.
- Hommelsheim, Renè,Hock, Katharina J.,Schumacher, Christian,Hussein, Mohanad A.,Nguyen, Thanh V.,Koenigs, Rene M.
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supporting information
p. 11439 - 11442
(2018/10/20)
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- Chromium(III)-Catalyzed Addition of Water and Alcohol to α,β-Unsaturated Ketones for the Synthesis of β-Hydroxyl and β-Alkoxyl Ketones in Aqueous Media
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An efficient chromium(III) chloride-catalyzed Michael-type reaction of water or alcohol with α,β-unsaturated ketones is developed. A variety of α,β-unsaturated ketones effectively reacted with either water or alcohols to give the corresponding β-hydroxyl ketones or β-alkoxyl ketones in modest to high yields with excellent compatibility to various functional groups. The approach was further utilized for the preparation of synthetically useful compounds containing tetrahydrofuran skeleton.
- Yun, Jin-Jin,Liu, Xuan-Yu,Deng, Wei,Chu, Xue-Qiang,Shen, Zhi-Liang,Loh, Teck-Peng
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p. 10898 - 10907
(2018/09/06)
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- Method for synthesizing alpha,beta-unsaturated aryl ketone compound from dimethyl sulfoxide and arylethanone
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The invention discloses a method for synthesizing an alpha,beta-unsaturated aryl ketone compound from dimethyl sulfoxide and arylethanone. According to the method, dimethyl sulfoxide and arylethanoneare subjected to a one-pot reaction in the presence of carboxylate and persulfate so as to produce the alpha,beta-unsaturated aryl ketone compound. The method uses dimethyl sulfoxide as a methylenation reagent and employs a one-pot process for high-selectivity high-yield synthesis of the alpha,beta-unsaturated aryl ketone compound from arylethanone; and the method is simple to operate, low in cost, friendly to environment and beneficial for industrial production.
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Paragraph 0044; 0045-0050; 0051-0056
(2018/03/24)
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- Method for synthesizing alpha,beta-unsaturated ketone compounds from dimethyl sulfoxide and ketone compounds
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The invention discloses a method for synthesizing alpha,beta-unsaturated ketone compounds from dimethyl sulfoxide and ketone compounds. According to the method, dimethyl sulfoxide and ketone compoundsare subjected to a one-pot reaction in the presence of carboxylate and persulfate so as to produce the alpha,beta-unsaturated ketone compounds. The method uses dimethyl sulfoxide as a methylenation reagent and employs a one-pot process for high-selectivity high-yield synthesis of the alpha,beta-unsaturated ketone compounds from the ketone compounds; and the method is simple to operate, low in cost, friendly to environment and beneficial for industrial production.
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Paragraph 0047-0049; 0056-0059
(2018/03/24)
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- Synthesis of 4-Acylpyrazoles from Saturated Ketones and Hydrazones Featured with Multiple C(sp3)-H Bond Functionalization and C-C Bond Cleavage and Reorganization
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In this paper, an efficient and convenient one-pot synthesis of diversely substituted 4-acylpyrazole derivatives via copper-catalyzed one-pot cascade reactions of saturated ketones with hydrazones is reported. Mechanistically, the formation of the title compounds involves the in situ formation of an enone intermediate through the dehydrogenation of a saturated ketone and the [2 + 3] cyclization of the enone with hydrazone followed by an aromatization-driven C-C bond cleavage and reorganization. To our knowledge, this is the first example in which the biologically and pharmaceutically important yet otherwise difficult-to-obtain 4-acylpyrazole derivatives are directly prepared from saturated ketones and hydrazones featured with multiple aliphatic C-H bond functionalization and C-C bond cleavage and reorganization. Compared with literature methods, this novel process has advantages such as simple and economical starting materials, a sustainable oxidant, excellent regioselectivity, and good efficiency.
- Tian, Miaomiao,Shi, Xiaonan,Zhang, Xinying,Fan, Xuesen
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p. 7363 - 7372
(2017/07/26)
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- Transition Metal-Free α-Csp3-H Methylenation of Ketones to Form C=C Bond Using Dimethyl Sulfoxide as Carbon Source
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A direct α-Csp3-H methylenation of arylketones to form C=C bond using dimethyl sulfoxide as one-carbon source is achieved under transition metal-free reaction condition. Various aryl ketone derivatives react readily with DMSO, producing the α,β-unsaturated carbonyl compounds in yields of 42 to 90%. This method features a transition metal-free reaction condition, wide substrate scope and using DMSO as novel one-carbon source to form C=C bond, thus providing an efficient and expeditious approach to an important class of α,β-unsaturated carbonyl compounds. Based on the preliminary experiments, a plausible mechanism of this transformation is disclosed.
- Liu, Yu-Feng,Ji, Peng-Yi,Xu, Jing-Wen,Hu, Yu-Qun,Liu, Qiang,Luo, Wei-Ping,Guo, Can-Cheng
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p. 7159 - 7164
(2017/07/26)
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- Enantioselective Synthesis of Quaternary Δ4- and Δ5-Dehydroprolines Based on a Two-Step Formal [3+2] Cycloaddition of α-Aryl and α-Alkyl Isocyano(thio)acetates with Vinyl Ketones
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A divergent synthesis of optically active quaternary Δ4- and Δ5-dehydro prolines is developed based on the first catalytic enantioselective conjugate addition of α-substituted isocyano(thio)acetates to vinyl ketones that is general for both α-aryl and α-alkyl isocyano(thio)acetates. The new tetrasubstituted C?N stereocenter is formed without the need of any metal salt due to a bifunctional tertiary amine/squaramide catalyst, featuring a bulky polyaryl sidearm and an unusually short squaramide diamide H???H interatomic distance in the solid state.
- Odriozola, Amaiur,Oiarbide, Mikel,Palomo, Claudio
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supporting information
p. 12758 - 12762
(2017/09/25)
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- Direct Synthesis of γ-Keto Sulfones from Allylic Alcohols: One-Pot Palladium(II)-Catalyzed Generation of Enones Followed by Water-Mediated 1,4-Addition of Organosulfinates
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Allylic alcohols were exploited as synthetic precursors of γ-keto sulfones. The reaction involved the one-pot generation of α,β-enones in situ from the allylic alcohols by using a PdII–dioxygen catalytic system and subsequent sulfa-Michael addition in the presence of water. Importantly, water was identified as a sustainable substitute for a toxic copper salt to promote organosulfonyl addition. Diverse examples of aromatic and aliphatic γ-keto sulfones were prepared. Specially, Ar–X (X = Br, Cl) bonds were tolerated, which indicated a chemoselective catalytic system for the preparation of halogen-bearing γ-keto sulfones. This one-pot method does not require an acid, a base, or isolation of any intermediate. Control experiments indicated that the active catalyst of the first step also promoted the subsequent C–S bond-formation reaction. Water was found to accelerate the reaction rate and to be involved in the protonolysis of the σ-alkylpalladium complex, as corroborated by deuterium incorporation.
- Vellakkaran, Mari,Andappan, Murugaiah M. S.,Nagaiah, Kommu,Nanubolu, Jagadeesh Babu
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supporting information
p. 3575 - 3583
(2016/07/28)
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- Morita-Baylis-Hillman Reaction of α,β-Unsaturated Ketones with Allylic Acetates by the Combination of Transition-Metal Catalysis and Organomediation
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An intermolecular Morita-Baylis-Hillman (MBH) reaction of α,β-unsaturated ketones with allylic acetates under the catalysis of 10 mol % of tetrakis(triphenylphosphine)palladium(0) and mediation of tributylphosphine has been developed in the presence of acetic acid, affording the desired α-coupling products. The MBH reaction has the advantages of good tolerance to many functional groups, excellent regioselectivity and E-stereoselectivity, and moderate to good yields.
- Li, Ya-Qiong,Wang, Hai-Jun,Huang, Zhi-Zhen
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p. 4429 - 4433
(2016/07/06)
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- Fluorine-containing three-membered ring compound, preparation method of fluorine-containing three-membered ring compound and preparation method of fluoroalkyl sulfonium salt
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The invention discloses a fluorine-containing three-membered ring compound shown in the formula V-a, V-b or V-c and a preparation method thereof. The preparation method comprises that in an organic solvent, fluoroalkyl sulfur ylide shown in the formula II
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Paragraph 0172; 0173; 0174; 0175; 0196; 0197
(2016/10/08)
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- Copper-Catalyzed Cyclopropanol Ring Opening Csp3-Csp3 Cross-Couplings with (Fluoro)Alkyl Halides
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Novel and general copper-catalyzed cyclopropanol ring opening cross-coupling reactions with difluoroalkyl bromides, perfluoroalkyl iodides, monofluoroalkyl bromides, and 2-bromo-2-alkylesters to synthesize various β-(fluoro)alkylated ketones are reported.
- Ye, Zhishi,Gettys, Kristen E.,Shen, Xingyu,Dai, Mingji
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supporting information
p. 6074 - 6077
(2016/01/09)
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- Solid-supported cross-metathesis and a formal alkane metathesis for the generation of biologically relevant molecules
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Solid-phase synthetic strategies toward the generation of libraries of biologically relevant molecules were developed using olefin cross-metathesis as a key step. It is remarkably the formal alkane metathesis based on a one-pot, microwave-assisted, ruthenium-catalyzed cross-metathesis and reduction to obtain Csp3-Csp3 linkages.
- Mndez, Luciana,Mata, Ernesto G.
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- Regioselective catalytic asymmetric C-alkylation of isoxazolinones by a base-free palladacycle-catalyzed direct 1,4-addition
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Isoxazolinones constitute a class of heterocycles utilized for the development of novel drug candidates. The cyclic oxime ester motif is also synthetically useful as it contains functional handles which have previously been used to provide access to an assortment of valuable compound classes not easily accessible by alternative approaches. However, asymmetric methods towards isoxazolinones are notoriously scarce. Herein we report the first catalytic asymmetric alkylations of isoxazolinones forming all-C-substituted quaternary stereocenters. The present studies were driven by the question of how to control the regioselectivity in the competition of different nucleophilic positions. The investigation of a direct 1,4-addition uncovered that a sterically demanding palladacycle catalyst directs the reactivity in the absence of a base nearly exclusively to the nucleophilic C atom, while at the same time it allows for high enantioselectivity and TONs up to 1900.
- Hellmuth, Tina,Frey, Wolfgang,Peters, Ren
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supporting information
p. 2788 - 2791
(2015/03/04)
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- 1,4-Diazabicyclo[2.2.2]octane-Promoted Aminotrifluoromethylthiolation of α,β-Unsaturated Carbonyl Compounds: N-Trifluoromethylthio-4-nitrophthalimide Acts as Both the Nitrogen and SCF3 Sources
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A novel difunctionalization reaction is described. It uses N-trifluoromethylthio-4-nitrophthalimide as the reagent, which serves as both the nitrogen and SCF3 sources. In the presence of DABCO (1,4-diazabicyclo[2.2.2]octane), the nitrogen and SCF3 groups can be incorporated into α,β-unsaturated carbonyl compounds easily and give versatile β-amino ketones and esters in good yields. This difunctionalization reaction features mild reaction conditions, high atom-economy, and efficient access to α-SCF3 amino acids.
- Xiao, Qing,He, Qijie,Li, Juncheng,Wang, Jun
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supporting information
p. 6090 - 6093
(2016/01/09)
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- Desulfonylative Methenylation of β-Keto Sulfones
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A one-step strategy for the synthesis of α-methenyl ketones from β-keto sufones is reported. Success of the methodology is elaborated for the synthesis of chromanones and isoflavanones in one-step.
- Pandey, Ganesh,Vaitla, Janakiram
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supporting information
p. 4890 - 4893
(2015/10/12)
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- Efficient synthesis of β-CF3/SCF3-substituted carbonyls via copper-catalyzed electrophilic ring-opening cross-coupling of cyclopropanols
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The first copper-catalyzed ring-opening electrophilic trifluoromethylation and trifluoromethylthiolation of cyclopropanols to form Csp3-CF3 and Csp3-SCF3 bonds have been realized. These transformations are effic
- Li, Yong,Ye, Zhishi,Bellman, Tabitha M.,Chi, Teng,Dai, Mingji
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supporting information
p. 2186 - 2189
(2015/05/13)
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- Diastereoselective Johnson-Corey-Chaykovsky trifluoroethylidenation
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(2,2,2-Trifluoroethyl)diphenylsulfonium triflate was found to be an efficient ylide reagent for the Johnson-Corey-Chaykovsky reaction to afford trifluoromethyl epoxides, cyclopropanes and aziridines. Interestingly, excellent but different diastereoselectivity was observed for these transformations. Both trifluoromethyl epoxides and cyclopropanes were obtained with trans-selectivity, whereas aziridines were obtained with cis-selectivity.
- Duan, Yaya,Zhou, Bin,Lin, Jin-Hong,Xiao, Ji-Chang
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supporting information
p. 13127 - 13130
(2015/08/18)
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- New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds
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Pyruvate kinase M2 (PKM2) is a key protein responsible for cancer's Warburg effect. Activation of PKM2 may alter aberrant metabolism in cancer cells, which suggests PKM2 as a tumor selective therapeutic target. In this paper, the lead compound 8 was first discovered as a new kind of PKM2 activator from a random screening of an in-house compound library. Then, a series of lead compound 8 analogs were designed, synthesized and evaluated for their activation of PKM2 and anticancer activities. 7-Azaindole analog 32 was identified as the most potent PKM2 activator. Compounds with potent enzyme activity also exhibited selective anti-proliferation activity on cancer cell lines HCT116, Hela and H1299 compared with non-tumor cell line BEAS-2B. The structure-activity relationships of these compounds were supported by molecular docking results. Preliminary pharmacological studies also showed that compound 32 arrests the cell cycle at the G2/M phase in HCT116 cell line.
- Zhang, Yu,Liu, Bin,Wu, Xingyu,Lei, Ridong,Ning, Xianling,Liu, Yu,Liu, Zhenming,Ge, Zemei,Li, Runtao,Yin, Yuxin
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p. 4815 - 4823
(2015/08/03)
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- Oxygen as single oxidant for two steps: Base-free one-pot Pd(ii)-catalyzed alcohol oxidation & arylation to halogen-intact β-aryl α,β-enones
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Using oxygen as the sole oxidant for two steps, we developed a new method to synthesize β-aryl α,β-enones by fine-tuning the Pd(ii)-catalyzed oxidation of allyl alcohol to subsequent arylation with arylboronic acids, arylboronic ester and aryltrifluoroborate salt. This one-pot green method does not require copper salt, base, and intermediate isolation. Halogen-bearing chalcones, dibenzylideneacetones and arylalkyl enones were synthesized in good yields. This journal is
- Vellakkaran, Mari,Andappan, Murugaiah M. S.,Nagaiah, Kommu
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p. 45490 - 45494
(2014/12/10)
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- DMF as carbon source: Rh-catalyzed α-methylation of ketones
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An unprecedented Rh-catalyzed direct methylation of ketones with N,N-dimethylformamide (DMF) is disclosed. The reaction shows a broad substrate scope, tolerating both aryl and alkyl ketones with various substituents. Mechanistic studies suggest that DMF delivers a methylene fragment followed by a hydride in the methylation process.
- Li, Yang,Xue, Dong,Lu, Wei,Wang, Chao,Liu, Zhao-Tie,Xiao, Jianliang
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supporting information
p. 66 - 69
(2014/01/23)
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- Stereoselective access to trisubstituted cyclopentanols from chiral unsaturated oxo esters by ketyl radical cyclization
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Substituted cyclopentanols with three contiguous stereocenters were prepared with impressive diastereocontrol through a samarium diiodide induced 5-exo-trig radical process. The chiral unsaturated oxo ester precursors were prepared with ee values up to 90 % from propionaldehyde through a two-step organocatalyzed aldolization and Wittig-Horner olefination reaction sequence. Copyright
- Feuillastre, Sophie,Pelotier, Beatrice,Piva, Olivier
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supporting information
p. 1753 - 1759
(2014/03/21)
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- Stereoselective Access to Trisubstituted Cyclopentanols from Chiral Unsaturated Oxo Esters by Ketyl Radical Cyclization
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Substituted cyclopentanols with three contiguous stereocenters were prepared with impressive diastereocontrol through a samarium diiodide induced 5-exo-trig radical process. The chiral unsaturated oxo ester precursors were prepared with ee values up to 90 % from propionaldehyde through a two-step organocatalyzed aldolization and Wittig-Horner olefination reaction sequence.
- Feuillastre, Sophie,Pelotier, Béatrice,Piva, Olivier
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supporting information
p. 1753 - 1759
(2015/10/05)
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- Enantioselective synthesis of 3-substituted 1,2-oxazinanes via organocatalytic intramolecular aza-Michael addition
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A highly enantioselective intramolecular 6-exo-trig aza-Michael addition was developed to afford chiral 3-substituted 1,2-oxazinanes in high yields (up to 99% yield) and good enantioselectivities (up to 98/2 er). These reactions were enabled by a quinine-derived primary-tertiary diamine as a catalyst and pentafluoropropionic acid (PFP) as a co-catalyst.
- Cheng, Shuanghua,Yu, Shouyun
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supporting information
p. 8607 - 8610
(2014/12/10)
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- N-Heterocyclic carbene-catalyzed double acylation of enones with benzils
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Thiazolium carbene-catalyzed reaction of aromatic 1,2-diketones with enones in aprotic solvents gave double acylation products in good yields, whereas hydroacylation products formed by Stetter reaction were not detected at all. These results suggested the generation of aroyloxyenamine species from the 1,2-diketones instead of hydroxyenamines (Breslow intermediates). This journal is
- Takaki, Ken,Ohno, Akira,Hino, Makoto,Shitaoka, Takashi,Komeyama, Kimihiro,Yoshida, Hiroto
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supporting information
p. 12285 - 12288
(2014/12/11)
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- Bi(OTf)3-catalyzed tandem Meyer-Schuster rearrangement and 1,4-addition to the resulting vinyl ketone
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Bi(OTf)3-catalyzed Meyer-Schuster rearrangement of electron-rich propargyl alcohols, followed by 1,4-addition of the resulting vinyl ketone, proceeded smoothly though Meyer-Schuster rearrangement of primary propargyl alcohols is rare. This tandem reaction can be extended to an intramolecular version, featuring a one-pot dihydroquinolone synthesis. (Chemical Equation Presented).
- Okamoto, Noriko,Sueda, Takuya,Yanada, Reiko
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p. 9854 - 9859
(2015/01/16)
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- Efficient and fast method for the preparation of Diaryl Ketones at room temperature
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Palladium-catalyzed cross-coupling reaction of arylboronic acids with acid chlorides at room temperature under phosphine-free conditions affords the corresponding aromatic ketones in excellent yields within short times. This synthetic method overcomes common disadvantages of Friedel-Crafts acylation procedures and is compatible with both electron-donating and electron-withdrawing substituents on the aryl ring of the acyl chlorides. Georg Thieme Verlag Stuttgart New York.
- Hajipour, Abdol Reza,Pourkaveh, Raheleh
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p. 1101 - 1105
(2014/05/20)
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- Oxa-Michael addition promoted by the aqueous sodium carbonate
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An efficient Michael addition of alcohols to activated alkenes promoted by sodium carbonate with water as reaction medium has been developed. The reaction provides a general, economical and environmentally friendly approach for the synthesis of β-alkoxycarbonyl compounds.
- Guo, Shi-Huan,Xing, Sheng-Zhu,Mao, Shuai,Gao, Ya-Ru,Chen, Wen-Liang,Wang, Yong-Qiang
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supporting information
p. 6718 - 6720
(2014/12/11)
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- Boron-trihalide-promoted regioselective ring-opening reactions of gem-difluorocyclopropyl ketones
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Boron trihalide-promoted ring-opening reactions of gem-difluorocyclopropyl ketones to give the corresponding β-trifluoromethyl ketones and β-halodifluoromethyl ketones were described. It was found that boron trihalides act as both Lewis acids and nucleophiles and the proximal bond prefers to cleave in this transformation.
- Yang, Tang-Po,Li, Qiang,Lin, Jin-Hong,Xiao, Ji-Chang
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supporting information
p. 1077 - 1079
(2014/01/17)
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