- Enantioselective Synthesis of N-Alkylamines through β-Amino C-H Functionalization Promoted by Cooperative Actions of B(C6F5)3and a Chiral Lewis Acid Co-Catalyst
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We disclose a catalytic method for β-C(sp3)-H functionalization of N-alkylamines for the synthesis of enantiomerically enriched β-substituted amines, entities prevalent in pharmaceutical compounds and used to generate different families of chiral catalysts. We demonstrate that a catalyst system comprising of seemingly competitive Lewis acids, B(C6F5)3, and a chiral Mg- or Sc-based complex, promotes the highly enantioselective union of N-alkylamines and α,β-unsaturated compounds. An array of δ-amino carbonyl compounds was synthesized under redox-neutral conditions by enantioselective reaction of a N-alkylamine-derived enamine and an electrophile activated by the chiral Lewis acid co-catalyst. The utility of the approach is highlighted by late-stage β-C-H functionalization of bioactive amines. Investigations in regard to the mechanistic nuances of the catalytic processes are described.
- Chang, Yejin,Cao, Min,Chan, Jessica Z.,Zhao, Cunyuan,Wang, Yuankai,Yang, Rose,Wasa, Masayuki
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supporting information
p. 2441 - 2455
(2021/02/16)
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- Zwitterion-Catalyzed Isomerization of Maleic to Fumaric Acid Diesters
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Fumaric acid diesters are important building blocks for organic synthesis. A class of zwitterionic organocatalysts based on an amide anion/iminium cation charge pair were found to be effective in catalyzing the isomerization of maleic acid diesters to give fumaric acid diesters. Comparison of the performance of different zwitterionic organocatalysts toward the reaction revealed that nonclassical hydrogen bonding was involved in the stabilization of the Michael adduct intermediate.
- Lam, Ying-Pong,Lam, Zachary,Yeung, Ying-Yeung
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p. 1183 - 1190
(2021/01/09)
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- Substrate-Controlled [5+1] Annulation of 5-Amino-1H-phenylpyrazoles with Alkenes: Divergent Synthesis of Multisubstituted 4,5-Dihydropyrazolo[1,5-a]quinazolines
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A new and efficient [5+1] annulation reaction for the first synthesis of 5,5-disubstituted 4,5-dihydropyrazolo[1,5-a]quinazolines is described. This transition-metal-free tandem cyclization was performed with 5-amino-1H-phenylpyrazole and readily availabl
- Jiang, Xunyuan,Wei, Xiaoyi,Lin, Fei,Zhang, Zhixiang,Yao, Guangkai,Yang, Shuai,Zhao, Weijing,Zhao, Chen,Xu, Hanhong
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supporting information
p. 3997 - 4003
(2020/06/17)
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- Generation and Reactivity of Electron-Rich Carbenes on the Surface of Catalytic Gold Nanoparticles
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The reactive nature of carbenes can be modulated, and ultimately reversed, by receiving additional electron density from a metal. Here, it is shown that Au nanoparticles (NPs) generate an electron-rich carbene on surface after transferring electron density to the carbonyl group of an in situ activated diazoacetate, as assessed by Fourier transformed infrared (FT-IR) spectroscopy, magic angle spinning nuclear magnetic resonance (MAS NMR), and Raman spectroscopy. Density functional theory (DFT) calculations support the observed experimental values and unveil the participation of at least three different Au atoms during carbene stabilization. The surface stabilized carbene shows an extraordinary stability against nucleophiles and reacts with electrophiles to give new products. These findings showcase the ability of catalytic Au NPs to inject electron density in energetically high but symmetrically allowed valence orbitals of sluggish molecules.
- Oliver-Meseguer, Judit,Boronat, Mercedes,Vidal-Moya, Alejandro,Concepción, Patricia,Rivero-Crespo, Miguel ángel,Leyva-Pérez, Antonio,Corma, Avelino
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supporting information
p. 3215 - 3218
(2018/03/13)
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- New aziridine-based inhibitors of cathepsin L-like cysteine proteases with selectivity for the Leishmania cysteine protease LmCPB2.8
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In the present work a series of aziridine-2,3-dicarboxylate inhibitors of papain-like cysteine proteases was designed, synthesized and tested. The compounds displayed selectivity for the parasitic protozoon Leishmania mexicana cathepsin L-like cysteine protease LmCPB2.8. The computational methods of homology modelling and molecular docking predicted some significant differences in the S2 pocket of LmCPB2.8 and cruzain, a related enzyme from Trypanosoma cruzi. Due to the presence of Tyr209 in LmCPB2.8 rather than Glu208 in cruzain sterically demanding, lipophilic ester groups (inhibitor 7d, 9d, 12d and 14d) are predicted to occupy the S2 pocket of the Leishmania protease, but do not form favorable interactions in cruzain, which is in common with our experimental results. Further, inhibitor 18 bearing a free carboxylic acid attached to the aziridine moiety showed a time-dependent inhibition of LmCPB2.8 (Ki = 0.41 μM; k2nd = 190,569 M?1 min?1). Docking results suggested a strong ionic interaction with the positively charged His163 of the active site. Biological and theoretical data confirm that the novel selective aziridine-based inhibitors are promising candidates for further optimization as LmCPB2.8 inhibitors.
- Fey, Philipp,Chartomatsidou, Roula,Kiefer, Werner,Mottram, Jeremy C.,Kersten, Christian,Schirmeister, Tanja
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p. 587 - 597
(2018/07/25)
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- Reductive Coupling of Acrylates with Ketones and Ketimines by a Nickel-Catalyzed Transfer-Hydrogenative Strategy
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Nickel-catalyzed coupling of benzyl acrylates with activated ketones and imines provides γ-butyrolactones and lactams, respectively. The benzyl alcohol byproduct released during the lactonization/lactamization event is relayed to the next cycle where it serves as the reductant for C?C bond formation. This strategy represents a conceptually unique approach to transfer-hydrogenative C?C bond formation, thus providing examples of reductive heterocyclizations where hydrogen embedded within an alcohol leaving group facilitates turnover.
- Buxton, Craig S.,Blakemore, David C.,Bower, John F.
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supporting information
p. 13824 - 13828
(2017/10/24)
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- The MOF-driven synthesis of supported palladium clusters with catalytic activity for carbene-mediated chemistry
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The development of catalysts able to assist industrially important chemical processes is a topic of high importance. In view of the catalytic capabilities of small metal clusters, research efforts are being focused on the synthesis of novel catalysts bearing such active sites. Here we report a heterogeneous catalyst consisting of Pd4 clusters with mixed-valence 0/+1 oxidation states, stabilized and homogeneously organized within the walls of a metal-organic framework (MOF). The resulting solid catalyst outperforms state-of-the-art metal catalysts in carbene-mediated reactions of diazoacetates, with high yields (>90%) and turnover numbers (up to 100,000). In addition, the MOF-supported Pd4 clusters retain their catalytic activity in repeated batch and flow reactions (>20 cycles). Our findings demonstrate how this synthetic approach may now instruct the future design of heterogeneous catalysts with advantageous reaction capabilities for other important processes.
- Fortea-Pérez, Francisco R.,Mon, Marta,Ferrando-Soria, Jesús,Boronat, Mercedes,Leyva-Pérez, Antonio,Corma, Avelino,Herrera, Juan Manuel,Osadchii, Dmitrii,Gascon, Jorge,Armentano, Donatella,Pardo, Emilio
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p. 760 - 766
(2017/07/04)
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- POLYGLYOXYLATES, MANUFACTURE AND USE THEREOF
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Self-immolative polymers degrade by an end-to-end depolymerisation mechanism in response to the cleavage of a stabilizing end-cap from the polymer terminus. Examples include homopolymers, mixed polymers including block copolymers, suitable for a variety of applications. A polyglyoxylate can be end-capped or capped with a linker as in a block copolymer.
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Page/Page column 24
(2015/11/27)
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- Polyglyoxylates: A versatile class of triggerable self-immolative polymers from readily accessible monomers
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Self-immolative polymers, which degrade by an end-to-end depolymerization mechanism in response to the cleavage of a stabilizing end-cap from the polymer terminus, are of increasing interest for a wide variety of applications ranging from sensors to controlled release. However, the preparation of these materials often requires expensive, multistep monomer syntheses, and the degradation products such as quinone methides or phthalaldehydes are potentially toxic to humans and the environment. We demonstrate here that polyglyxoylates can serve as a new and versatile class of self-immolative polymers. Polymerization of the commercially available monomer ethyl glyoxylate, followed by end-capping with a 6-nitroveratryl carbonate, provides a poly(ethyl glyoxylate) that depolymerizes selectively upon irradiation with UV light, ultimately generating ethanol and the metabolic intermediate glyoxylic acid hydrate. To access polyglyoxylates with different properties, the polymerization and end-capping approach can also be extended to other glyoxylate monomers including methyl glyoxylate, n-butyl glyoxylate, and benzyl glyoxylate, which can be easily prepared from their corresponding fumaric or maleic acid derivatives. Random copolymers of these monomers with ethyl glyoxylate can also be prepared. Furthermore, using a multifunctional end-cap that is UV-responsive and also enables the conjugation of another polymer block via an azide-alkyne "click" cycloaddition, amphiphilic self-immolative block copolymers are also prepared. These block copolymers self-assemble into micelles in aqueous solution, and their poly(ethyl glyoxylate) blocks rapidly depolymerize upon UV irradiation. Overall, these strategies are expected to greatly expand the utility of self-immolative polymers by providing access for the first time to self-immolative polymers with tunable properties that can be readily obtained from simple monomers and can be designed to depolymerize into nontoxic products.
- Fan, Bo,Trant, John F.,Wong, Andrew D.,Gillies, Elizabeth R.
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supporting information
p. 10116 - 10123
(2014/08/05)
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- Esterification of dicarboxylic acids with benzyl alcohol under the action of the microwave radiation
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Reaction of dicarboxylic acid with benzyl alcohol under the microwave irradiation proceeds faster as compared to the thermal conditions. The main reaction products are alkyl dicarboxylates, and the monoester and dibenzyl ether are formed as the side products. A proposal about the nature of the nonthermal effect in the reactions stimulated by the microwave irradiation is considered.
- Aver'yanov,Batrakova,Samuilov,Spiridonova,Kochnev,Galibeev,Gnezdilov
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experimental part
p. 1920 - 1923
(2009/02/08)
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- Syntheses of potential degradation products of phenylephrine in OTC products
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Compound 1 and 2 are potential major degradants in over the counter (OTC) products containing phenylephrine HCl and dexbrompheniramine maleate or chlorpheniramine maleate. Compound 2 matches the unknown peak in the solution of stressed active and excipient and thus was identified as the correct degradation product. Whether the degradation product is racemic or chiral is not known. This article describes synthesis of both compounds. Compound 2 will be useful as an analytical standard for quantitative analysis of the major degradant in OTC products of phenylephrine HCl and dexbrompheniramine maleate or chlorpheniramine maleate. Copyright Taylor & Francis Group, LLC.
- Chan,Kong, Jianshe,McNamara, Paul,Wong, Jesse K.
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p. 2252 - 2260
(2008/09/21)
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- Highly chemo- and stereoselective intermolecular coupling of diazoacetates to give cis-olefins by using Grubbs second-generation catalyst
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Highly stereoselective formation of cis-2-ene-1,4-diesters by homo- and heterocoupling of α-diazoacetates in the presence of Grubbs second-generation catalyst is demonstrated. The dual reactivity of the catalyst in alkene metathesis and diazocoupling has been exploited in the synthesis of 12-26-membered macrocyclic dienyl dilactones by one-pot carbene dimerisation/ring-closing metathesis.
- Hodgson, David M.,Angrish, Deepshikha
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p. 3470 - 3479
(2008/02/08)
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- PHARMACEUTICAL COMPOSITIONS AS INHIBITORS OF DIPEPTIDYL PEPTIDASE-IV (DPP-IV)
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The present invention relates to compounds which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, Syndrome X, hyperinsulinemia, obesity, atherosclerosis, and various immunomodulatory diseases.
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