83-13-6Relevant articles and documents
α-Arylation of diethyl malonate via enolate with bases in a heterogeneous phase
Aramendía, María A.,Borau, Victoriano,Jiménez, César,Marinas, José M.,Ruiz, José R.,Urbano, Francisco J.
, p. 2847 - 2849 (2002)
The influence of various heterogeneous bases on yield and selectivity in the α-arylation of diethyl malonate was studied. Barium hydroxide was found to provide excellent results in this context. The bases used can be easily removed from the reaction medium by filtration.
Evaluation of the Structure-Activity Relationship of Microtubule-Targeting 1,2,4-Triazolo[1,5- a]pyrimidines Identifies New Candidates for Neurodegenerative Tauopathies
Oukoloff, Killian,Nzou, Goodwell,Varricchio, Carmine,Lucero, Bobby,Alle, Thibault,Kovalevich, Jane,Monti, Ludovica,Cornec, Anne-Sophie,Yao, Yuemang,James, Michael J.,Trojanowski, John Q.,Lee, Virginia M.-Y.,Smith, Amos B.,Brancale, Andrea,Brunden, Kurt R.,Ballatore, Carlo
, p. 1073 - 1102 (2021/02/03)
Studies in tau and Aβ plaque transgenic mouse models demonstrated that brain-penetrant microtubule (MT)-stabilizing compounds, including the 1,2,4-triazolo[1,5-a]pyrimidines, hold promise as candidate treatments for Alzheimer's disease and related neurodegenerative tauopathies. Triazolopyrimidines have already been investigated as anticancer agents; however, the antimitotic activity of these compounds does not always correlate with stabilization of MTs in cells. Indeed, previous studies from our laboratories identified a critical role for the fragment linked at C6 in determining whether triazolopyrimidines promote MT stabilization or, conversely, disrupt MT integrity in cells. To further elucidate the structure-activity relationship (SAR) and to identify potentially improved MT-stabilizing candidates for neurodegenerative disease, a comprehensive set of 68 triazolopyrimidine congeners bearing structural modifications at C6 and/or C7 was designed, synthesized, and evaluated. These studies expand upon prior understanding of triazolopyrimidine SAR and enabled the identification of novel analogues that, relative to the existing lead, exhibit improved physicochemical properties, MT-stabilizing activity, and pharmacokinetics.
Ketone Synthesis from Benzyldiboronates and Esters: Leveraging α-Boryl Carbanions for Carbon-Carbon Bond Formation
Lee, Boran,Chirik, Paul J.
supporting information, p. 2429 - 2437 (2020/03/03)
An alkoxide-promoted method for the synthesis of ketones from readily available esters and benzyldiboronates is described. The synthetic method is compatible with a host of sterically differentiated alkyl groups, alkenes, acidic protons α to carbonyl groups, tertiary amides, and aryl rings having common organic functional groups. With esters bearing α-stereocenters, high enantiomeric excess was maintained during ketone formation, establishing minimal competing racemization by deprotonation. Monitoring the reaction between benzyldiboronate and LiOtBu in THF at 23 °C allowed for the identification of products arising from deborylation to form an α-boryl carbanion, deprotonation, and alkoxide addition to form an "-ate" complex. Addition of 4-trifluoromethylbenzoate to this mixture established the α-boryl carbanion as the intermediate responsible for C-C bond formation and ultimately ketone synthesis. Elucidation of the role of this intermediate leveraged additional bond-forming chemistry and enabled the one-pot synthesis of ketones with α-halogen atoms and quaternary centers with four-different carbon substituents.
Aryltrifluoromethylative cyclization of unactivated alkenes by the use of PhICF3Cl under catalyst-free conditions
Guo, Jia,Xu, Cong,Liu, Xiaowei,Wang, Mang
supporting information, p. 2162 - 2168 (2019/02/27)
A concise and catalyst-free aryltrifluoromethylative cyclization of unactivated alkenes has been developed herein. The use of PhICF3Cl as a powerful trifluoromethylating agent allows easy transformations. A set of trifluoroethylated carbocycles and aza-hereocycles were efficiently synthesized in good yield and selectivity. A broad substrate scope, mild reaction conditions, and easy operation would make this method well-suited for applications.
Copper(I)-USY as a Ligand-Free and Recyclable Catalyst for Ullmann-Type O-, N-, S-, and C-Arylation Reactions: Scope and Application to Total Synthesis
Garnier, Tony,Danel, Mathieu,Magné, Valentin,Pujol, Anthony,Bénéteau, Valérie,Pale, Patrick,Chassaing, Stefan
, p. 6408 - 6422 (2018/05/31)
The copper(I)-doped zeolite CuI-USY proved to be a versatile, efficient, and recyclable catalyst for various Ullmann-type coupling reactions. Easy to prepare and cheap, this catalytic material enables the arylation and heteroarylation of diverse O-, N-, S-, and C-nucleophiles under ligand-free conditions while exhibiting large functional group compatibility. The facility of this catalyst to promote C-O bond formation was further demonstrated with the total synthesis of 3-methylobovatol, a naturally occurring diaryl ether of biological relevance. From a mechanistic viewpoint, two competitive pathways depending on the nature of the nucleophile and consistent with the obtained results have been proposed.
Method for greenly synthesizing 5-hydroxy-5-alkyl disubstituted barbituric acid derivative by amine catalysis of air oxidation
-
Paragraph 0025; 0027; 0029, (2019/01/07)
The invention relates to the field of oxidative synthesis, and in particular, relates to a 5-hydroxy-5-alkyl disubstituted barbituric acid derivative greenly synthesized by amine catalysis of air oxidation and a method thereof. The amine-catalyzed oxidation reaction of a 5-substituted 1,3-dimethylbarbituric acid derivative is studied; reaction catalysts and solvents are screened, hydroxylation ofalpha-C-H of 5-aryl or benzyl substituted barbituric acid compounds is found out to be realized through catalytic reaction under different conditions. The method has the following characteristics: (1)air is used as the source of hydroxyl functional groups, so the requirements of green development are met; (2) easily available and cheap alkali R3N rather than expensive metal catalysts is used; and(3) stoichiometric harmful phosphine compounds are prevented from being used as additives and reductants.
AlCl3 catalyzed coupling of: N-benzylic sulfonamides with 2-substituted cyanoacetates through carbon-nitrogen bond cleavage
Hu, Chen,Hong, Gang,Qian, Xiaofei,Kim, Kwang Rim,Zhu, Xiaoyan,Wang, Limin
supporting information, p. 4984 - 4991 (2017/07/10)
A new cross-coupling reaction of N-benzylic sulfonamides with 2-substituted cyanoacetates for the synthesis of 2-substituted benzylbenzene was reported. In the presence of AlCl3, a broad range of N-benzylic sulfonamides reacted smoothly with 2-substituted cyanoacetates to afford structurally diverse benzylbenzenes in moderate to excellent yields. The conversion could be enlarged to gram-scale efficiently. The practicability of this approach was further manifested in the synthesis of a related bioactive agent with high anti-inflammatory activity.
O2 activation at a trispyrazolylborato nickel(II) malonato complex
Hoof,Sallmann,Herwig,Braun-Cula,Limberg
supporting information, p. 16792 - 16795 (2017/12/26)
To support mechanistic inferences made for an iron-based dioxygenase model, a nickel analogue, i.e. a TpNi-malonate (1) was prepared. 1 proved to represent a rare case of a nickel complex reacting with O2 in a controlled manner-mechanistically different from the iron case-and leads to hydroxylation of the malonate.
UV-mediated decomposition of diazomalonates in benzene: Unexpected access to functionalized bicyclo[3.2.0]heptane skeleton
Chiang, Yi-Jung,Zhu, Jia-Liang
supporting information, p. 3081 - 3084 (2017/07/17)
Upon irradiation with 300-nm UV light, the photolysis of diazomalonates in benzene unexpectedly affords 2,6-dicarboxylate bicyclo[3.2.0]hepta-2,6-dienes in low yields. These products are proven to be derived from cyclohepta-1,3,5-triene intermediates presumably via a tandem 1,5-carboxylate migration/[2+2] cycloaddition sequence.
Protonation and transformations of α-diazo-β-dicarbonyl compounds in superacids: generation of the strongest carbon-centered cationic electrophiles at the protonation of diazomalonates in Friedel–Crafts reactions
Satumov, Eugeniy T.,Medvedev, Jury J.,Nilov, Denis I.,Sandzhieva, Maria A.,Boyarskaya, Irina A.,Nikolaev, Valerij A.,Vasilyev, Aleksander V.
, p. 4835 - 4844 (2016/07/18)
Protonation of diazodiketones N2C(COR)2in Br?nsted superacids (TfOH, FSO3H, TfOH–SbF5) gives rise to stable and non-reactive O,O-diprotonated at carbonyl oxygens species N2C(C(=OH+)R)2, which were studied by means of1H and13C NMR. Diazomalonates N2C(CO2Alk)2, contrary to diazodiketones, react with TfOH or HF, releasing nitrogen and producing triflates of oxymalonates TfOCH(CO2Alk)2or fluoromalonates FCH(CO2Alk)2, respectively. Diazoketoesters N2C(COR)(CO2Alk) react in the same way only with TfOH, but not with HF. The reactions of diazomalonates with arenes ArH (benzene, toluene, xylenes) in TfOH solution yield corresponding Friedel–Crafts reaction products ArCH(CO2Alk)2. According to performed DFT calculations, trication+CH(C(=OH+)OMe)2, a possible intermediate, which is derived from protonation of dimethyl diazomalonate, should be the strongest cationic carbon-centered electrophile known up to date.
