- Electrochemical oxidative cyclization of: N -allylcarboxamides: Efficient synthesis of halogenated oxazolines
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Herein, we reported an efficient and sustainable intramolecular electrochemical cyclization of N-allylcarboxamides for the synthesis of various halogenated oxazolines. This method was conducted in a simple undivided cell by employing lithium halogen salts
- He, Yanyang,Liu, Chenwei,Wu, Xiao-Feng,Yin, Yanzhao,Yin, Zhiping
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supporting information
p. 663 - 667
(2022/01/22)
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- Stereoselective Oxidative Cyclization ofN-Allyl Benzamides to Oxaz(ol)ines
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This study presents an enantioselective oxidative cyclization ofN-allyl carboxamides via a chiral triazole-substituted iodoarene catalyst. The method allows the synthesis of highly enantioenriched oxazolines and oxazines, with yields of up to 94% and enantioselectivities of up to 98% ee. Quaternary stereocenters can be constructed and, besidesN-allyl amides, the corresponding thioamides and imideamides are well tolerated as substrates, giving rise to a plethora of chiral 5-memberedN-heterocycles. By applying a multitude of further functionalizations, we finally demonstrate the high value of the observed chiral heterocycles as strategic intermediates for the synthesis of other enantioenriched target structures.
- Abazid, Ayham H.,Hollwedel, Tom-Niklas,Nachtsheim, Boris J.
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supporting information
p. 5076 - 5080
(2021/07/19)
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- Sequential catalytic carbonylation reactions for sustainable synthesis of biologically relevant entities
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The sustainable synthesis of highly functionalised formylcarboxamide compounds with biological relevance is reported through a sequential aminocarbonylation/hydroformylation approach. The optimisation of palladium-catalysed aminocarbonylation of iodoaromatic substrates, using allylamine as nucleophile was first performed, with molybdenum hexacarbonyl as alternative CO source versus gaseous carbon monoxide. The combination of microwave irradiation with molybdenum hexacarbonyl allowed to selectively prepare a set of N-heterocyclic-based allylcarboxamides. Subsequent rhodium-catalysed hydroformylation of the allylcarboxamide intermediates led to the preparation of new pyridine, pyrazoline and chalcone derivatives containing both carboxamide and formyl moieties.
- Carrilho, Rui M. B.,Damas, Liliana,Gonzalez, Andreia C. S.,Pereira, Mariette M.,Pineiro, Marta,Rodrigues, Fábio M. S.
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- A Next-Generation Air-Stable Palladium(I) Dimer Enables Olefin Migration and Selective C?C Coupling in Air
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We report a new air-stable PdI dimer, [Pd(μ-I)(PCy2tBu)]2, which triggers E-selective olefin migration to enamides and styrene derivatives in the presence of multiple functional groups and with complete tolerance of air. The same dimer also triggers extremely rapid C?C coupling (alkylation and arylation) at room temperature in a modular and triply selective fashion of aromatic C?Br, C?OTf/OFs, and C?Cl bonds in poly(pseudo)halogenated arenes, displaying superior activity over previous PdI dimer generations for substrates that bear substituents ortho to C?OTf.
- Kundu, Gourab,Rissanen, Kari,Schoenebeck, Franziska,Sperger, Theresa
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supporting information
p. 21930 - 21934
(2020/10/02)
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- Electrochemical Chalcogenation of β,γ-Unsaturated Amides and Oximes to Corresponding Oxazolines and Isoxazolines
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The current report represents a transition-metal-free synthesis of oxazoline and isoxazoline derivatives by a tandem electro-oxidative chalcogenation-cyclization process. Both C?Se and C?S bond-forming protocols were developed without using any external oxidant and the reaction was performed at room temperature, open to the air. Using this methodology, 29 substituted oxazoline and 16 substituted isoxazoline derivatives were synthesized with up to 91% isolated yield. (Figure presented.).
- Baidya, Mrinmay,De Sarkar, Suman,Mahanty, Kingshuk,Maiti, Debabrata,Mallick, Samrat
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supporting information
(2020/02/04)
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- Preparation of Heterocycles via Visible-Light-Driven Aerobic Selenation of Olefins with Diselenides
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The aerobic dehydrogenative cyclization of alkenes with easily accessible diselenides facilitated by visible light is reported. Notably, the features of this transition-metal-free protocol are pronounced efficiency and practicality, good functional group
- Zhang, Qing-Bao,Yuan, Pan-Feng,Kai, Liang-Lin,Liu, Kai,Ban, Yong-Liang,Wang, Xue-Yang,Wu, Li-Zhu,Liu, Qiang
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supporting information
p. 885 - 889
(2019/02/14)
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- Electrochemical oxidative cyclization of olefinic carbonyls with diselenides
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The tandem cyclization of olefinic carbonyls with easily accessible diselenides facilitated by electrochemical oxidation has been successfully developed, which provides an environmentally friendly method for the construction of C-Se and C-O bonds simultaneously. A series of seleno dihydrofurans and seleno oxazolines, bearing fragile heterocycles, subtle C-I bonds and supernumerary vinyl groups, were forged using this elegant chelation strategy. Neither metal catalysts nor external chemical oxidants are required to promote this transformation.
- Guan, Zhipeng,Wang, Yunkun,Wang, Huamin,Huang, Yange,Wang, Siyuan,Tang, Hongding,Zhang, Heng,Lei, Aiwen
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supporting information
p. 4976 - 4980
(2019/09/30)
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- Electrochemical Fluorocyclization of N-Allylcarboxamides to 2-Oxazolines by Hypervalent Iodine Mediator
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A resource saving protocol for the synthesis of 5-fluoromethyl-2-oxazolines by using electrochemistry has been realized. Thereby, a hypervalent iodine species I(III) is generated by anodic oxidation in the presence of Et3N·5HF and mediates the
- Haupt, John D.,Berger, Michael,Waldvogel, Siegfried R.
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supporting information
p. 242 - 245
(2019/01/04)
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- Silver-Promoted Synthesis of 5-[(Pentafluorosulfanyl)methyl]-2-oxazolines
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The synthesis of 5-[(pentafluorosulfanyl)methyl]-2-oxazolines is reported. The use of a silver promoter allows the intramolecular cyclization of N-[2-chloro-3-(pentafluorosulfanyl)propyl]amide to occur without elimination of the chlorine atom, a reaction
- Gilbert, Audrey,Bertrand, Xavier,Paquin, Jean-Fran?ois
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supporting information
p. 7257 - 7260
(2018/11/23)
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- Fluorocyclisation via I(I)/I(III) catalysis: A concise route to fluorinated oxazolines
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Herein, we describe a catalytic fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor, whilst HF serves as both a fluoride source and Br?nsted acid activator. The C(sp3)–F bond of the mono-fluoromethyl unit and the C(sp3)–O bond of the ring are aligned in a synclinal relationship thereby engaging in stabilising hyperconjugative interactions with vicinal, electron-rich σ-bonds (σC–C→σ*C–F and σC–H→σ*C–O). This manifestation of the stereoelectronic gauche effect was established by X-ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class.
- Daniliuc, Constantin G.,Gilmour, Ryan,Kehr, Gerald,Meyer, Stephanie,Scheidt, Felix,Thiehoff, Christian,Yilmaz, Gülay
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supporting information
p. 1021 - 1027
(2020/05/06)
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- XtalFluor-E mediated proto-functionalization of: N -vinyl amides: Access to N -acetyl N, O -acetals
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XtalFluor-E has been extensively used in a broad range of reactions in the past few years. Here we report its use with protic nucleophiles in a catalytic manner for the in situ generation of protons that lead to the proto-functionalization of activated ol
- Yi,Gholami,Morrow,Borhan
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supporting information
p. 9570 - 9574
(2017/11/30)
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- Copper-Catalyzed Divergent Trifluoromethylation/Cyclization of Unactivated Alkenes
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Most of the precedent copper-catalyzed trifluoromethylation reactions of unactivated alkenes concern terminal alkenes, and these processes are terminated in elimination, or nucleophilic addition, or semipinacol rearrangement, or C-H bond functionalization steps. In this study, we develop a trifluoromethylation method for both unactivated terminal and internal alkenes to enable divergent late-stage radical cyclization and achieve high molecular complexity. These cyclizations are well consistent with Baldwin's rule. Furthermore, a kinetic isotope effect (KIE) study and control reactions were conducted, and a plausible mechanism is proposed.
- Zheng, Jing,Deng, Ziyang,Zhang, Yan,Cui, Sunliang
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supporting information
p. 746 - 751
(2016/03/09)
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- Divergent Synthesis of Imidazoles and Quinazolines via Pd(OAc)2-Catalyzed Annulation of N-Allylamidines
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A Pd(OAc)2-catalyzed divergent synthesis of multisubstituted imidazoles and quinazolines from N-allylamidines has been developed. In the presence of oxidant O2 from air and/or a ligand and Pd(OAc)2, imidazoles were obtaine
- Xu, Li,Li, Hongxian,Liao, Ziyang,Lou, Kaiyan,Xie, Hexin,Li, Hao,Wang, Wei
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supporting information
p. 3434 - 3437
(2015/07/28)
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- Aryl amide small-molecule inhibitors of microRNA miR-21 function
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MicroRNAs (miRNAs) are single stranded RNA molecules of ~22 nucleotides that negatively regulate gene expression. MiRNAs are involved in fundamental cellular processes, such as development, differentiation, proliferation, and survival. MiRNA misregulation has been linked to various human diseases, most notably cancer. MicroRNA-21 (miR-21), a well-established oncomiR, is significantly overexpressed in many types of human cancers, thus rendering miR-21 a potential therapeutic target. Using a luciferase-based reporter assay under the control of miR-21 expression, a high-throughput screen of >300,000 compounds led to the discovery of a new aryl amide class of small-molecule miR-21 inhibitors. Structure-activity relationship (SAR) studies resulted in the development of four aryl amide derivatives as potent and selective miR-21 inhibitors. The intracellular levels of various miRNAs in HeLa cells were analyzed by qRT-PCR revealing specificity for miR-21 inhibition over other miRNAs. Additionally, preliminary mechanism of action studies propose a different mode of action compared to previously reported miR-21 inhibitors, thus affording a new chemical probe for future studies.
- Naro, Yuta,Thomas, Meryl,Stephens, Matthew D.,Connelly, Colleen M.,Deiters, Alexander
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supporting information
p. 4793 - 4796
(2015/10/28)
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- Iron-catalyzed direct synthesis of amides from methylarenes
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An efficient, green and first catalytic process has been developed for the direct synthesis of amides from readily available petroleum by-products (methylarenes) and amines using an iron catalyst. In this new catalytic reaction, the methyl group of the me
- Srinivas Kotha, Surya,Badigenchala, Sindhura,Sekar, Govindasamy
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p. 1437 - 1445
(2015/05/19)
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- Co2(CO)8 as a convenient in situ CO source for the direct synthesis of benzamides from aryl halides (Br/I) via aminocarbonylation
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A fast, mild, and functional group tolerant method for the direct synthesis of benzamides from aryl halides (Br, I) via aminocarbonylation, using solid Co2(CO)8 as a convenient CO source, has been demonstrated. The developed method is applicable to a wide variety of 1° and cyclic and acyclic 2°amines. Nitro substituted (o, m and p) aryl halides have easily been converted to the corresponding benzamides, without the reduction of the nitro group, in high yields using this in situ carbonylation methodology under microwave irradiation.
- Baburajan, Poongavanam,Elango, Kuppanagounder P.
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supporting information
p. 1006 - 1010
(2015/02/19)
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- Co2(CO)8 as a convenient in situ CO source for the direct synthesis of benzamides from aryl halides (Br/I) via aminocarbonylation
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A fast, mild, and functional group tolerant method for the direct synthesis of benzamides from aryl halides (Br, I) via aminocarbonylation, using solid Co2(CO)8 as a convenient CO source, has been demonstrated. The developed method is applicable to a wide variety of 1 and cyclic and acyclic 2 amines. Nitro substituted (o, m and p) aryl halides have easily been converted to the corresponding benzamides, without the reduction of the nitro group, in high yields using this in situ carbonylation methodology under microwave irradiation.
- Baburajan, Poongavanam,Elango, Kuppanagounder P.
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supporting information
p. 1006 - 1010
(2014/02/14)
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- Iodine(III)-promoted synthesis of oxazolines from N-allylamides
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PhI(OAc)2 (activated by BF3·OEt2) has been used to promote the oxidative cyclization of N-allylamides to give oxazolines. The reaction products are formed in high yield and, when a branched allylic amine is used, high diastereoselectivity. Initial mechanistic experiments suggest that the final C-O bond is formed from a reactive tight ion pair, rather than a neutral external nucleophile.
- Moon, Nicholas G.,Harned, Andrew M.
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supporting information
p. 2960 - 2963
(2013/06/27)
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- Microwave-assisted, Mo(CO)6-mediated, palladium-catalyzed amino-carbonylation of aryl halides using allylamine: from exploration to scale-up
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Palladium-catalyzed aminocarbonylations of various (hetero)aryl halides with allylamine using Mo(CO)6 as a solid, in situ CO source, were explored. Microwave-enhanced conditions proved to be highly useful in promoting the conversions in a mere 10-20 min with various (hetero)aryl iodides, bromides and chlorides. The scale-up of a microwave-enhanced aminocarbonylation to 25 mmol scale was performed successfully.
- Appukkuttan, Prasad,Axelsson, Linda,der Eycken, Erik Van,Larhed, Mats
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p. 5625 - 5628
(2008/12/22)
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- The triphenyl phosphite-chlorine reagent in the synthesis of pyrroles from N-allylamides
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A novel application of (PhO)3P-Cl2 chemistry to the synthesis of 2-substituted and 2,3-disubstituted pyrroles from N-allyl-amides is illustrated. A mild procedure is used to generate the imino chloride intermediates, which are subseq
- Spaggiari, Alberto,Vaccari, Daniele,Davoli, Paolo,Prati, Fabio
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p. 995 - 998
(2007/10/03)
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- Synthesis of cyclopropylpyrrolidines via reaction of N-allyl-N-propargylamides with a molybdenum carbene complex. Effect of substituents and reaction conditions
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Previous studies have demonstrated that group 6 carbene complexes react with α,ω-enynes to form vinylcyclopropane derivatives in good to excellent yield, and that the length and composition of the tether between the alkyne and the alkene often has a dramatic impact on the viability of this reaction pathway. The reactivity of allylpropargyl amine derivatives with pentacarbonyl(1-methoxypentylidene)molybdenum(0) (14a) was investigated in order to provide further insight into the steric and electronic factors controlling this reaction. Treatment of allylpropargyl amines with 14a failed to produce the desired cyclization products while treatment of allylpropargyl amides with 14a led to the expected cyclopropylpyrrolidine systems in good to excellent yields. Higher yields are obtained when the reaction is conducted in a sealed vial in the presence of atmospheric oxygen.
- Harvey, Daniel F.,Sigano, Dina M.
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p. 2268 - 2272
(2007/10/03)
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- Kinetics and Mechanisms of the Aminolysis of N-Hydroxysuccinimide Esters in Aqueous Buffers
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Rate constants for the aminolysis of the N-hydroxysuccinimide (NHS) ester of p-methoxybenzoic acid, in aqueous buffer systems (20percent dioxane), have been determined under pseudo-first-order conditions.For the amines studied (pKa = 7.60-11.1), the data fit the rate expression kobsd - kOH--> = k1free.This rate equation is in contrast to the two-term rate equation (kobsd = k1 + k22) obtained for this reaction in anhydrous dioxane (Cline, G.W.; Hanna, S.B.J.Am.Chem.Soc 1987, 109, 3087) and is suggestive of a disproportionate decrease in the catalyzed vs the uncatalyzed reaction path upon changing from a nonaqueous to an aqueous solvent system.The correlation of amine basicity with the nucleophilic rate constant, k1, yields a slope βnuc = 1.0.The magnitude of βnuc, in terms of a reaction mechanism where a tetrahedral intermediate is formed in a fast preequilibrium followed by rate-determining breakdown to products, reflects the sensitivity to changes in charge accumulation in the formation of the tetrahedral intermediate.The resultant increased rate constants, with increased basicity, are due to the effect of an increased concentration of the tetrahedral intermediate.A qualitative evaluation of the literature and current data concerning the leaving ability of N-hydroxy esters, in comparison to phenyl esters (equivalent acyl groups and nucleophiles), reveals that, with leaving groups of comparable basicity, the nucleophilic rate constants for N-hydroxy esters are about 2 orders of magnitude greater than that for phenyl esters.
- Cline, Gary W.,Hanna, Samir B.
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p. 3583 - 3586
(2007/10/02)
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