- Catalyst-Free Decarbonylative Trifluoromethylthiolation Enabled by Electron Donor-Acceptor Complex Photoactivation
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A catalyst- and additive-free decarbonylative trifluoromethylthiolation of aldehyde feedstocks has been developed. This operationally simple, scalable, and open-to-air transformation is driven by the selective photoexcitation of electron donor-acceptor (EDA) complexes, stemming from the association of 1,4-dihydropyridines (donor) with N-(trifluoromethylthio)phthalimide (acceptor), to trigger intermolecular single-electron transfer events under ambient- and visible light-promoted conditions. Extension to other electron acceptors enables the synthesis of thiocyanates and thioesters, as well as the difunctionalization of [1.1.1]propellane. The mechanistic intricacies of this photochemical paradigm are elucidated through a combination of experimental efforts and high-level quantum mechanical calculations [dispersion-corrected (U)DFT, DLPNO-CCSD(T), and TD-DFT]. This comprehensive study highlights the necessity for EDA complexation for efficient alkyl radical generation. Computation of subsequent ground state pathways reveals that SH2 addition of the alkyl radical to the intermediate radical EDA complex is extremely exergonic and results in a charge transfer event from the dihydropyridine donor to the N-(trifluoromethylthio)phthalimide acceptor of the EDA complex. Experimental and computational results further suggest that product formation also occurs via SH2 reaction of alkyl radicals with 1,2-bis(trifluoromethyl)disulfane, generated in-situ through combination of thiyl radicals. (Figure presented.).
- Lipp, Alexander,Badir, Shorouk O.,Dykstra, Ryan,Gutierrez, Osvaldo,Molander, Gary A.
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supporting information
p. 3507 - 3520
(2021/06/11)
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- Visible-Light-Induced Regioselective Dicarbonylation of Indolizines with Oxoaldehydes via Direct C-H Functionalization
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A metal-free system for regioselective dehydrogenative cross-couplings between indolizines and oxoaldehydes catalyzed by visible light under mild conditions has been described. As an atom economical and eco-friendly protocol, the reaction proceeds in good yields using inexpensive, readily available visible-light sources and the environmentally friendly oxidant oxygen. Various valuable 1,2-dicarbonyl derivatives attached to an indolizine core were easily accessed by the direct dicarbonylation of the sp2 C-H bond.
- Teng, Lili,Liu, Xiang,Guo, Pengfeng,Yu, Yue,Cao, Hua
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supporting information
p. 3841 - 3845
(2020/05/08)
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- Asymmetric Conjugate Addition of α-Cyanoketones to Benzoyl Acrylonitrile Derivatives Using a Diaminomethylenemalononitrile Organocatalyst
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A diaminomethylenemalononitrile (DMM) organocatalyst was used to efficiently promote asymmetric conjugate addition of various α-cyanoketones to benzoyl acrylonitrile derivatives. The corresponding 1,5-dicarbonyl compounds containing vicinal tertiary and quaternary stereogenic centers are versatile synthetic intermediates and were obtained in good yields and with excellent enantioselectivities (up to 96% ee). The present study describes the first successful examples of asymmetric conjugate addition reactions of α-cyanoketones with benzoyl acrylonitriles. In addition, the DMM organocatalyst can be recovered and reused up to five times without significant loss of either catalytic activity or enantioselectivity.
- Akutsu, Hiroshi,Nakashima, Kosuke,Kanetsuna, Yuta,Kawada, Masahiro,Hirashima, Shin-Ichi,Miura, Tsuyoshi
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p. 3874 - 3880
(2020/10/06)
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- Stereocontrolled Synthesis of 1,4-Dicarbonyl Compounds by Photochemical Organocatalytic Acyl Radical Addition to Enals
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We report a visible-light-mediated organocatalytic strategy for the enantioselective acyl radical conjugate addition to enals, leading to valuable 1,4-dicarbonyl compounds. The process capitalizes upon the excited-state reactivity of 4-acyl-1,4-dihydropyridines that, upon visible-light absorption, can trigger the generation of acyl radicals. By means of a chiral amine catalyst, iminium ion activation of enals ensures a stereoselective radical trap. We also demonstrate how the combination of this acylation process with a second catalyst-controlled bond-forming event allows to selectively access the full matrix of all possible stereoisomers of the resulting 2,3-substituted 1,4-dicarbonyl products.
- Goti, Giulio,Bieszczad, Bartosz,Vega-Pe?aloza, Alberto,Melchiorre, Paolo
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supporting information
p. 1213 - 1217
(2019/01/04)
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- Oxidative C-C Bond Cleavage for the Synthesis of Aryl Carboxylic Acids from Aryl Alkyl Ketones
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A metal-free and one-pot two-step synthesis of aryl carboxylic acids from aryl alkyl ketones has been achieved. The reactions were performed with iodine as the catalyst, DMSO and TBHP as the oxidants. Under the optimal reaction conditions, a number of aryl alkyl ketones could be converted into their corresponding aryl carboxylic acids in good to excellent yields (up to 94%).
- Xu, Liang,Wang, Shengpeng,Chen, Bajin,Li, Meichao,Hu, Xinquan,Hu, Baoxiang,Jin, Liqun,Sun, Nan,Shen, Zhenlu
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supporting information
p. 1505 - 1509
(2018/05/25)
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- Enantioselective Cyanosilylation of α,α-Dialkoxy Ketones by Using Phosphine-Thiourea Dual-Reagent Catalysis
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The first highly enantioselective cyanosilylation of α,α-dialkoxy ketones enabled by a dual-reagent catalysis has been developed. With the combination of a chiral bifunctional phosphine-thiourea and methyl acrylate, the key organophosphorus zwitterion intermediate was generated in situ as a novel Lewis base, which catalyzed the enantioselective cyanosilylation reaction in excellent yields (up to 99 %) with good-to-excellent enantioselectivities (up to 94 % ee).
- Yu, Qi-Wen,Wu, Lu-Ping,Kang, Tian-Chen,Xie, Jin,Sha, Feng,Wu, Xin-Yan
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supporting information
p. 3992 - 3996
(2018/07/31)
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- Visible-light assisted one-pot preparation of aryl glyoxals from acetoarylones via in-situ arylacyl bromides formation: Selenium-free approach to acetoarylones oxidation
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A novel visible-light (blue LEDs: hν?=?425?±?15?nm) photocatalyzed one-pot method for the synthesis of electronically diverse aryl glyoxals in good to excellent yields from acetoarylones and green regents such as air, vitamin C and dioxane dibromide has been described. In addition, an application of the current methodology has been demonstrated for the oxidation of monoamine oxidase-B inhibitors, i.e., 1-(4-((4-fluorobenzyl)oxy)phenyl)ethanone and 1-(3-((4-chlorobenzyl)oxy)phenyl)ethanone. This finding may serves as a valuable alternative to the traditional acetoarylones oxidation reactions conducted using selenium dioxide a harmful and unselective reagent known to simultaneously oxidize allylic, benzylic, [sbnd]CH3and so on.
- Natarajan, Palani,Manjeet,Kumar, Naveen,Devi, Sapna,Mer, Kalyani
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supporting information
p. 658 - 662
(2017/01/25)
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- Organocatalytic Enantioselective Acyloin Rearrangement of α-Hydroxy Acetals to α-Alkoxy Ketones
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We report an unprecedented organocatalytic enantioselective acyloin rearrangement of α,α-disubstituted α-hydroxy acetals. In the presence of a catalytic amount of chiral binol-derived N-triflyl phosphoramide, α-hydroxy acetals rearranged to α-alkoxy ketones in good to high yields with high enantioselectivities. Formation of an ion pair between the in situ generated oxocarbenium ion and the chiral phosphoramide anion was proposed to be responsible for the highly efficient transfer of chirality. Conditions for removal of cyclohexyl and cyclopentyl groups from the corresponding α-alkoxy ketones were uncovered underpinning their potential general utility as hydroxy protecting groups. Conversion of the rearranged products to the enantioenriched α-hydroxy ketone, 1,2-diol, β-amino alcohol and 1,4-dioxane was also documented.
- Wu, Hua,Wang, Qian,Zhu, Jieping
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supporting information
p. 5858 - 5861
(2017/05/12)
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- Palladium-catalyzed decarboxylative, decarbonylative and dehydrogenative C(sp2)-H acylation at room temperature
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Over the past few decades, an impressive array of C-H activation methodology has been developed for organic synthesis. However, due to the inherent inertness of the C-H bonds (e.g. ~110 kcal mol-1 for the cleavage of C(aryl)-H bonds) harsh reaction conditions have been realized to overcome high energetic transition states resulting in a limited substrate scope and functional group tolerance. Therefore, the development of mild C-H functionalization protocols is in high demand to exploit the full potential of the C-H activation strategy in the synthesis of a complex molecular framework. Although, electron-rich substrates undergo electrophilic metalation under relatively mild conditions, electron-deficient substrates proceed through a rate-limiting C-H insertion under forcing conditions at high temperature. In addition, a stoichiometric amount of toxic silver salt is frequently used in palladium catalysis to facilitate the C-H activation process which is not acceptable from the environmental and industrial standpoint. We report herein, a Pd(ii)-catalyzed decarboxylative C-H acylation of 2-arylpyridines with α-ketocarboxylic acids under mild conditions. The present protocol does not require stoichiometric silver(i) salts as additives and proceeds smoothly at ambient temperature. A novel decarbonylative C-H acylation reaction has also been accomplished using aryl glyoxals as acyl surrogates. Finally, a practical C-H acylation via a dehydrogenative pathway has been demonstrated using commercially available benzaldehydes and aqueous hydroperoxides. We also disclose that acetonitrile solvent is optimal for the acylation reaction at room temperature and has a prominent role in the reaction outcome. Control experiments suggest that the acylation reaction via decarboxylative, decarbonylative and dehydrogenative proceeds through a radical pathway. Thus we disclose a practical protocol for the sp2 C-H acylation reaction.
- Hossian, Asik,Manna, Manash Kumar,Manna, Kartic,Jana, Ranjan
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supporting information
p. 6592 - 6603
(2017/08/16)
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- Experimental and Theoretical Studies on Iron-Promoted Oxidative Annulation of Arylglyoxal with Alkyne: Unusual Addition and Migration on the Aryl Ring
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An Fe(III)-promoted oxidative annulation reaction was developed for the synthesis of 1,2-naphthoquinones. A variety of substituted arylglyoxals and internal alkynes undergo the transformation in the presence of FeCl3 at room temperature to afford the 1,2-naphthoquinone products in good yields in a short reaction time. Interestingly, the products show unusual pseudomigration of the substituent on the arene ring of arylglyoxals. A possible mechanism involving Fe(III)-promoted formation of a vinyl cation from arylglyoxal and alkyne, electrophilic addition of the vinyl cation to the ipso carbon of the aryl group to give a spiral intermediate, and then migration of the keto carbon to the ortho carbon was proposed as key steps and verified using quantum mechanics.
- Hung, Chen-Hsun,Gandeepan, Parthasarathy,Cheng, Lin-Chieh,Chen, Liang-Yu,Cheng, Mu-Jeng,Cheng, Chien-Hong
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supporting information
p. 17015 - 17021
(2017/12/06)
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- Rh-catalyzed asymmetric hydrogenation of racemic aldimines via dynamic kinetic resolution
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Catalyzed by a rhodium complex of P-stereogenic diphosphine ligand trichickenfootphos (TCFP), asymmetric hydrogenation of racemic aldimines via dynamic kinetic resolution has been realized for the preparation of chiral arylglycines with good yields and enantioselectivities.
- Fan, Dongyang,Lu, Jian,Liu, Yang,Zhang, Zhenfeng,Liu, Yangang,Zhang, Wanbin
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p. 5541 - 5547
(2016/08/05)
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- Design and synthesis of coumarin-glyoxal hybrids for spermicidal and antimicrobial actions: A dual approach to contraception
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Today there is an urgent need for safe and effective dual-purpose contraceptive agents, which can simultaneously prevent unintended pregnancies and sexually transmitted infections (STI). There are several naturally occurring antimicrobial and antibiotic drugs (novobiocin, coumermycin and chlorobiocin) reported in the literature, which are based on 4-hydroxy coumarins as the active pharmacophore. Based on these interesting reports, we designed and synthesized a library of new 4-hydroxy coumarin derivatives and evaluated them for spermicidal activity. Among the tested compounds, two compounds (2a and 2d) displayed better activity (greater than 95% sperm immobilization at 0.5 mM concentration) than the positive control nonoxynol-9 (N-9). Furthermore, all the compounds were screened for antimicrobial activity against different strains of Trichomonas vaginalis and two compounds (2c and 2h) exhibited potent activity as compared to the reference drug metronidazole. The cytotoxicity assay showed that most of these compounds were safer than the N-9 against the human cervical HeLa cell line and normal vaginal flora Lactobacillus jensenii strains. The studies have demonstrated that compound (2a) is a potential lead to develop a dually active vaginal contraceptive.
- Gupta, Swati,Kushwaha, Bhavana,Srivastava, Akansha,Maikhuri, Jagdamba Prasad,Sankhwar, Satya N.,Gupta, Gopal,Dwivedi, Anil Kumar
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p. 76288 - 76297
(2016/08/30)
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- Syntheses, Cholinesterases Inhibition, and Molecular Docking Studies of Pyrido[2,3-b]pyrazine Derivatives
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Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3-b]pyrazines (6a-6q) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3-b]pyrazines showed 3-(3′-nitrophenyl)pyrido[2,3-b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC50 values of 0.466 ± 0.121 and 1.89 ± 0.05 μm, respectively. The analogues 3-(3′-methylphenyl)pyrido[2,3-b]pyrazine 6c and 3-(3′-fluorophenyl)pyrido[2,3-b]pyrazine 6f were found to be selective inhibition for BChE with IC50 values of 0.583 ± 0.052 μm and AChE with IC50 value of 0.899 ± 0.10 μm, respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors. A series of pyrido[2,3-b]pyrazine (6a-6q) derivatives has been synthesized and evaluated for inhibitory activities against cholinesterases; acetylcholinesterase, and butyrylcholinesterase. Molecular docking of active compounds was also performed to suggest the putative binding modes with cholinesterases.
- Hameed, Abdul,Zehra, Syeda T.,Shah, Syed J. A.,Khan, Khalid M.,Alharthy, Rima D.,Furtmann, Norbert,Bajorath, Jürgen,Tahir, Muhammad N.,Iqbal, Jamshed
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p. 1115 - 1120
(2015/10/28)
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- Iodine-mediated oxidative annulation for one-pot synthesis of pyrazines and quinoxalines using a multipathway coupled domino strategy
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An efficient iodine-mediated oxidative annulation of aryl acetylenes-arylethenes-aromatic ketones with 1,2-diamines for the synthesis of pyrazines and regioselective synthesis of quinoxalines is presented. A multipathway coupled domino approach has been developed for the one-pot synthesis of 1,4-diazines with high functional group compatibility.
- Viswanadham, K. K. Durga Rao,Prathap Reddy, Muktapuram,Sathyanarayana, Pochampalli,Ravi, Owk,Kant, Ruchir,Bathula, Surendar Reddy
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supporting information
p. 13517 - 13520
(2015/01/09)
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- Metal-free oxidative amidation of 2-oxoaldehydes: A facile access to α-ketoamides
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A novel and efficient method for the synthesis of α-ketoamides, employing a dimethyl sulfoxide (DMSO)-promoted oxidative amidation reaction between 2-oxoaldehydes and amines under metal-free conditions is presented. Furthermore, mechanistic studies supported an iminium ion-based intermediate as a central feature of reaction wherein C1-oxygen atom of α-ketoamides is finally derived from DMSO.
- Mupparapu, Nagaraju,Khan, Shahnawaz,Battula, Satyanarayana,Kushwaha, Manoj,Gupta, Ajai Prakash,Ahmed, Qazi Naveed,Vishwakarma, Ram A.
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supporting information
p. 1152 - 1155
(2014/03/21)
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- Synthesis of 6-Substituted 3,5-diaryl-1,2,4-triazines as Potential Herbicidal Agents
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A variety of 6-substituted 3,5-diaryl-1,2,4-triazines were synthesized.These diaryltriazines, which incorporate a triazine nucleus substituted by two aryl moietes, comprise a new class of bleaching herbicides.The structure-activity relationships were prov
- Konno, Shoetsu,Osawa, Noriko,Yamanaka, Hiroshi,Sanemitsu, Yuzuru,Kawamura, Shinichi,Sakaki, Masaharu
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p. 838 - 842
(2007/10/02)
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- Structure-activity Relationship of Herbicidal 2,3-Dicyano-5-Substituted Pyrazines
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Sixty six 2,3-dicyano-5-substituted pyrazines were synthesized and their herbicidal activities against barnyard grass were measured in pot tests to clarify the relationship between chemical structure and activity.The activity of 59 derivatives was related parabolically to the hydrophobic substituent parameter at the 5-position of the pyrazine ring.
- Nakamura, Akira,Ataka, Toshiei,Segawa, Hirozo,Takeuchi, Yasutomo,Takematsu, Tetsuo
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p. 1555 - 1560
(2007/10/02)
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