120790-93-4Relevant academic research and scientific papers
Addition of malonic esters to azoalkenes generated in situ from α-bromo- and α-chlorohydrazones
Kokuev, Aleksandr O.,Ioffe, Sema L.,Sukhorukov, Alexey Yu.
, (2021/10/04)
Michael addition of malonic esters to azoalkenes generated in situ from α-bromo- and α-chlorohydrazones was accomplished. Both aliphatic and aromatic substrates bearing different functional groups are tolerated. The use of a strong base (sodium hydride) for generation of azoalkenes and deprotonation of malonate was found to be essential for a successful coupling. Synthetic potential of the obtained β-hydrazonoalkylmalonates was demonstrated by their smooth conversion into five- and six-membered N-heterocycles, functionalized hydrazides, 2-(2-oxo-2-arylethyl)malonates and 2-arylethylmalonates.
Development of Br?nsted Base-Photocatalyst Hybrid Systems for Highly Efficient C-C Bond Formation Reactions of Malonates with Styrenes
Ba?, Sebastian,Kobayashi, Shū,Yamashita, Yasuhiro
, p. 10546 - 10550 (2020/11/09)
Br?nsted base-photocatalyst hybrid systems have been developed for reactions of malonates with styrene derivatives. The concept of this process lies in the photo-oxidation of catalytic amounts of the enolate to form reactive radicals that react with alken
Radical-Mediated Strategies for the Functionalization of Alkenes with Diazo Compounds
Su, Yong-Liang,Liu, Geng-Xin,Liu, Jun-Wen,Tram, Linh,Qiu, Huang,Doyle, Michael P.
supporting information, p. 13846 - 13855 (2020/09/21)
One of the most common reactions of diazo compounds with alkenes is cyclopropanation, which occurs through metal carbene or free carbene intermediates. Alternative functionalization of alkenes with diazo compounds is limited, and a methodology for the addition of the elements of Z-CHR2 (with Z = H or heteroatom, and CHR2 originates from N2 CR2) across a carbon-carbon double bond has not been reported. Here we report a novel reaction of diazo compounds utilizing a radical-mediated addition strategy to achieve difunctionalization of diverse alkenes. Diazo compounds are transformed to carbon radicals with a photocatalyst or an iron catalyst through PCET processes. The carbon radical selectively adds to diverse alkenes, delivering new carbon radical species, and then forms products through hydroalkylation by thiol-assisted hydrogen atom transfer (HAT), or forms azidoalkylation products through an iron catalytic cycle. These two processes are highly complementary, proceed under mild reaction conditions, and show high functional group tolerance. Furthermore, both transformations are successfully performed on a gram-scale, and diverse γ-amino esters, γ-amino alcohols, and complex spirolactams are easily prepared with commercially available reagents. Mechanistic studies reveal the plausible pathways that link the two processes and explain the unique advantages of each.
Catalytic Hydrogenolysis of Enantioenriched Donor–Acceptor Cyclopropanes Using H2 and Palladium on Charcoal
Sone, Yoshitomo,Kimura, Yumi,Ota, Ryotaro,Mochizuki, Takehito,Ito, Junki,Nishii, Yoshinori
, p. 2842 - 2847 (2017/05/29)
The hydrogenolysis of enantioenriched donor–acceptor (D–A) cyclopropanes using H2 (1 atm) and a catalytic amount of palladium on charcoal gave trans-α-alkoxycarbonyl-β-benzyl-γ-lactones or β-substituted γ-aryl-α,α-diesters with high enantiomeric excess. The reaction was also used as a key step in the asymmetric total synthesis of yatein with high ee and excellent dr. This demonstrates the utility of this new protocol for the asymmetric synthesis of trans-α,β-disubstituted γ-butyrolactones. D–A cyclopropanes containing electron-withdrawing groups at the β-position were not susceptible to hydrogenolysis under these conditions. The reductive ring-opening of a D–A cyclopropane using D2 instead of H2 generated the corresponding monodeuterated product.
Regioselective Hydrogenolysis of Donor-Acceptor Cyclopropanes with Zn-AcOH Reductive System
Ivanov, Konstantin L.,Villemson, Elena V.,Latyshev, Gennadij V.,Bezzubov, Stanislav I.,Majouga, Alexander G.,Melnikov, Mikhail Ya.,Budynina, Ekaterina M.
, p. 9537 - 9549 (2017/09/23)
A convenient low-cost method for regioselective ring-opening of donor-acceptor cyclopropanes with the Zn-AcOH reductive system was developed. The general character of the method was displayed via efficient reduction of a representative series of 2-(het)arylcyclopropane-1,1-diesters as well as donor-acceptor cyclopropanes with other types of electron-withdrawing activating groups. This method opens a rapid access to γ-substituted propyl-1,1-diesters, ketoesters, cyanoesters, cyanoamides, dinitriles, etc., many of which are not readily accessible with alternative methods. The utility of the synthesized compounds was demonstrated by transforming them into valuable acyclic and cyclic compounds (including pharmacologically relevant carbazoles, δ-lactams, and oxindole derivatives).
Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
supporting information, p. 9067 - 9089 (2017/11/14)
Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
BACTERIAL EFFLUX PUMP INHIBITORS
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Paragraph 0262-0263, (2016/10/11)
Disclosed herein are compounds of formula I: and salts thereof. Also disclosed are compositions comprising of compounds of formula I and methods using compounds of formula I.
The prins cascade cyclization reaction for the synthesis of angularly-fused tetrahydropyran and piperidine derivatives
Subba Reddy,Kumar, Harish,Borkar, Prashant,Yadav,Sridhar
, p. 1993 - 1999 (2013/05/22)
2-Arylethylbut-3-en-1-ol is found to undergo smooth Prins cascade reactions with various aldehydes in the presence of Sc(OTf)3 (10 mol-%) and a stoichiometric amount of TsOH to afford the corresponding trans-fused hexahydro-1H-benzo[f]isochrome
Selective photochemical monoalkylation of active methylene compounds by alkenes. A green pathway for carbon-carbon bond formation
Ohashi, Maki,Nakatani, Keisuke,Maeda, Hajime,Mizuno, Kazuhiko
experimental part, p. 161 - 170 (2010/12/18)
A novel photochemical method for selective α-monoalkylation of active methylene compounds has been developed. Aryl substituted alkenes and an aliphatic diene can be used as alkyl sources for these reactions, which proceed via polycyanoarene sensitized, photoinduced electron transfer pathways that are promoted using very mild conditions (ambient temperature, without noble metals and halogens, and with weak bases such as alkali metal carbonate). The reactions that comprise the new synthetic methods developed in this effort are both safe and environmentally friendly. Especially noteworthy is the fact that photochemical alkylation reactions of β-ketoesters (e.g., acetoacetic and malonic esters) can be used in the place of conventional strong base promoted processes.
Enzymatic Synthesis of Chiral Monosubstituted Malonates in Organic Solvents
Shapira, Michal,Gutman, Arie L.
, p. 1689 - 1700 (2007/10/02)
Prochiral stereospecificity of enzymes in organic solvents was used to develop a strategy for the formation of heretofore unknown chiral monosubstituted malonate diesters with high enantiomeric excess.The enzymatic reaction involved transesterification of symmetrical monosubstituted dimethyl malonates with benzyl alcohol, exploiting the ability of lipases to discriminate between the enantiotopic ester groups of the symmetrical malonate molecule.This enzymatic approach is not feasible in aqueous solutions because the activated malonic hydrogen invariably undergoes fast exchange accompanied by racemisation.The synthetic utility of this method was further demonstrated by converting the configurationally unstable mixed methyl benzyl diesters into the corresponding half esters, which were in turn selectively reduced into configurationally stable and synthetically useful hydroxyesters.
