2294-71-5Relevant academic research and scientific papers
Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters
Wang, Peng-Fei,Yu, Jiao,Guo, Kai-Xin,Jiang, Sheng-Peng,Chen, Ji-Jun,Gu, Qiang-Shuai,Liu, Ji-Ren,Hong, Xin,Li, Zhong-Liang,Liu, Xin-Yuan
, p. 6442 - 6452 (2022/04/19)
The enantioconvergent radical C(sp3)-C(sp2) cross-coupling of alkyl halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good functional group tolerance. The key to the success is the rational design of hemilabile N,N,N-ligands by mounting steric hindrance at the ortho position of one coordinating quinoline ring. Thus, the newly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliver enantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utility in the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.
Asymmetric Aminations and Kinetic Resolution of Acyclic α-Branched Ynones
He, Faqian,Shen, Guosong,Yang, Xiaoyu
supporting information, p. 15 - 20 (2021/11/20)
An efficient method for asymmetric synthesis of acyclic α-tertiary amine derivatives has been achieved through enantioselective aminations of α-branched ynones with azodicarboxylates enabled by chiral phosphoric acid catalysis. Moreover, kinetic resolution of racemic starting material was realized under these conditions, which gave access to valuable enantioenriched α-substituted ketones. A wide array of α-aryl and alkyl-substitutions, and the substituted alkynyl groups were well compatible with this method, producing both the amination products and the recovered ketones with good to high enantioselectivities.
Iodoarene-Catalyzed Oxyamination of Unactivated Alkenes to Synthesize 5-Imino-2-Tetrahydrofuranyl Methanamine Derivatives
Deng, Xiao-Jun,Liu, Hui-Xia,Zhang, Lu-Wen,Zhang, Guan-Yu,Yu, Zhi-Xiang,He, Wei
, p. 235 - 253 (2021/01/09)
Reported here is the room-temperature metal-free iodoarene-catalyzed oxyamination of unactivated alkenes. In this process, the alkenes are difunctionalized by the oxygen atom of the amide group and the nitrogen in an exogenous HNTs2 molecule. This mild and open-air reaction provided an efficient synthesis to N-bistosyl-substituted 5-imino-2-tetrahydrofuranyl methanamine derivatives, which are important motifs in drug development and biological studies. Mechanistic study based on experiments and density functional theory calculations showed that this transformation proceeds via activation of the substrate alkene by an in situ generated cationic iodonium(III) intermediate, which is subsequently attacked by an oxygen atom (instead of nitrogen) of amides to form a five-membered ring intermediate. Finally, this intermediate undergoes an SN2 reaction by NTs2 as the nucleophile to give the oxygen and nitrogen difunctionalized 5-imino-2-tetrahydrofuranyl methanamine product. An asymmetric variant of the present alkene oxyamination using chiral iodoarenes as catalysts also gave promising results for some of the substrates.
Photocatalytic Giese-Type Reaction with Alkylsilicates Bearing C,O-Bidentate Ligands
Morofuji, Tatsuya,Matsui, Yu,Ohno, Misa,Ikarashi, Gun,Kano, Naokazu
supporting information, p. 6713 - 6718 (2021/02/26)
Herein, a photocatalytic Giese-type reaction with alkylsilicates bearing C,O-bidentate ligands as stable alkyl radical precursors has been reported. The alkylsilicates were prepared in one step from organometallic reagents. Not only primary, secondary, and tertiary alkyl radicals, but also elusive methyl radicals, could be generated by using the present reaction system. The generated radicals were trapped by electron-deficient olefins bearing various functional groups to give the desired alkyl adducts. The silicon byproduct can be recovered after the photoreaction. The radical generation process was investigated by theoretical calculations, which provided an insight into the facile generation of methyl radicals from methylsilicate bearing C,O-bidentate ligands.
Photocatalytic Hydromethylation and Hydroalkylation of Olefins Enabled by Titanium Dioxide Mediated Decarboxylation
Zhu, Qilei,Nocera, Daniel G.
, p. 17913 - 17918 (2020/12/04)
A versatile method for the hydromethylation and hydroalkylation of alkenes at room temperature is achieved by using the photooxidative redox capacity of the valence band of anatase titanium dioxide (TiO2). Mechanistic studies support a radical-based mechanism involving the photoexcitation of TiO2 with 390 nm light in the presence of acetic acid and other carboxylic acids to generate methyl and alkyl radicals, respectively, without the need for stoichiometric base. This protocol is accepting of a broad scope of alkene and carboxylic acids, including challenging ones that produce highly reactive primary alkyl radicals and those containing functional groups that are susceptible to nucleophilic substitution such as alkyl halides. This methodology highlights the utility of using heterogeneous semiconductor photocatalysts such as TiO2 for promoting challenging organic syntheses that rely on highly reactive intermediates.
Harnessing Applied Potential: Selective β-Hydrocarboxylation of Substituted Olefins
Alkayal, Anas,Buckley, Benjamin R.,Malkov, Andrei V.,Montanaro, Stephanie,Tabas, Volodymyr,Wright, Iain A.
supporting information, (2020/02/13)
The construction of carboxylic acid compounds in a selective fashion from low value materials such as alkenes remains a long-standing challenge to synthetic chemists. In particular, β-addition to styrenes is underdeveloped. Herein we report a new electrosynthetic approach to the selective hydrocarboxylation of alkenes that overcomes the limitations of current transition metal and photochemical approaches. The reported method allows unprecedented direct access to carboxylic acids derived from β,β-trisubstituted alkenes, in a highly regioselective manner.
Palladium-Catalyzed Alkoxycarbonylation of sec-Benzylic Ethers
Beller, Matthias,Jackstell, Ralf,Maes, Bert U. W.,Schneider, Carolin
supporting information, (2020/02/25)
Herein, we report the palladium-catalyzed synthesis of 3-arylpropionate esters starting from secondary benzylic ethers. With this investigation it could be shown that ethers are suitable starting materials in addition to the established carbonylation reactions of olefins, alcohols, or aryl halides.
Palladium catalyzed hydroesterification of substituted alkenes under microwave conditions
Du Plessis, Maretha,Marais, Charlene,Bezuidenhoudt, Barend C. B.
supporting information, p. 40 - 48 (2020/09/16)
While several catalyst systems have been utilized in the hydroesterification or methoxycarbonylation of alkenes or equivalent substrates, these reactions are conventionally performed in autoclave reactor systems under high CO pressure (20-70 bar) and thermal heating (70 - 110 oC). In this paper, the first methoxycarbonylation reactions performed in a microwave reactor fitted with a gas-Addition accessory system are reported on and compared to the same reactions performed under conventional heating in an autoclave reactor. Thus 1-octene, styrene, allylbenzene, o-and p-methoxyallylbenzene and β-methylstyrene were subjected to methoxycarbonylation over a palladium acetate-aluminum triflate catalyst system at 12 bar and 95 oC. Results obtained indicated the methoxycarbonylation of these alkenes to be much faster under microwave conditions when compared to conventional heating and improvements in conversion ranged between 3 and 5% for the more reactive substrates (1-octene and styrene) and 6 - 20% for the allylbenzenes and β-methylstyrene.
PYRAZOLOTRIAZOLOPYRIMIDINE DERIVATIVES AS A2A RECEPTOR ANTAGONIST
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Paragraph 0516; 0518, (2019/11/04)
Disclosed herein is a pyrazolotriazolopyrimidine derivative or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof useful as an A2A receptor antagonist, and a pharmaceutical composition comprising the same. Also disclosed herein is a method of treating cancer using the pyrazolotriazolopyrimidine derivative or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as an A2A receptor antagonist.
Modeling and optimization of lipase-catalyzed hydrolysis for production of (S)-2-phenylbutyric acid enhanced by hydroxyethyl-β-cyclodextrin
Zhang, Panliang,Cheng, Qing,Xu, Weifeng,Tang, Kewen
, p. 96 - 103 (2019/05/27)
An efficient reactive system was established to produce (S)-2-phenylbutyric acid (2-PBA) through the enzymatic enantioselective hydrolysis of 2-phenylbutyrate ester (2-PBAE) in aqueous medium. Lipase CALA from Canadian antarctica and hexyl 2-phenylbutyrate (2-PBAHE) were identified upon screening as the best enzyme and substrate, respectively. Adding hydroxyethyl-β-cyclodextrin (HE-β-CD) to improve the solubility of the substrate resulted in a 1.5 times increase in substrate conversion while retaining a high enantioselectivity compared with that when HE-β-CD was not added. The effects of lipase concentration, substrate concentration and HE-β-CD concentration, temperature, pH, and reaction time on enantiomeric excess and conversion rate were investigated, and the optimal conditions were identified using response surface methodology (RSM). Under the optimal conditions, namely 50 mg/mL lipase CALA, 30 mmol/L substrate, 60 mmol/L HE-β-CD, pH of 6.5, temperature of 83 °C and reaction time of 18 h, the enantiomeric excess and overall conversion rate were 96.05% and 27.28%, respectively. This work provides an efficient alternative method for improving the conversion of aromatic ester substrates by including β-cyclodextrin in an aqueous hydrolysis reaction system.
