- Chemo- and Regioselective Anionic Fries Rearrangement Promoted by Lithium Amides under Aerobic Conditions in Sustainable Reaction Media
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A straightforward and efficient protocol to promote the metalation/anionic Fries rearrangements of O-aryl carbamates, using for the first time a lithium amide as metalating agent under aerobic/ambient-friendly reaction conditions, is reported. This approach enables the sustainable preparation of salicylamide derivatives with high levels of chemoselectivity within ultrafast reaction times, working at room temperature in the presence of air/moisture, and using environmentally responsible cyclopentyl methyl ether as a solvent. Furthermore, the regioselective manipulation of O-2-tolyl carbamates has been accomplished using interchangeably alkyllithiums or lithium amides, with an unexpected beneficial contribution from the employment of biorenewable protic eutectic mixtures as non-innocent reaction media.
- Antenucci, Achille,Blangetti, Marco,Bolzoni, Paola,De Nardi, Federica,Ghinato, Simone,Prandi, Cristina
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- Rhoda-Electrocatalyzed Bimetallic C?H Oxygenation by Weak O-Coordination
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Rhodium-electrocatalyzed arene C?H oxygenation by weakly O-coordinating amides and ketones have been established by bimetallic electrocatalysis. Likewise, diverse dihydrooxazinones were selectively accessed by the judicious choice of current, enabling twofold C?H functionalization. Detailed mechanistic studies by experiment, mass spectroscopy and cyclovoltammetric analysis provided support for an unprecedented electrooxidation-induced C?H activation by a bimetallic rhodium catalysis manifold.
- Tan, Xuefeng,Massignan, Leonardo,Hou, Xiaoyan,Frey, Johanna,Oliveira, Jo?o C. A.,Hussain, Masoom Nasiha,Ackermann, Lutz
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supporting information
p. 13264 - 13270
(2021/05/06)
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- Aryl Carbamates: Mechanisms of Orthosodiations and Snieckus-Fries Rearrangements
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Aryl carbamates are orthometalated by sodium diisopropylamide (NaDA) in tetrahydrofuran. The resulting arylsodiums undergo Snieckus-Fries rearrangement to give orthoacylated phenols in good yield. The intermediate arylsodiums and resulting orthoacylated phenolates are suggested to be monomeric. The rate-limiting step in the two-step sequence depends on the steric demands of the carbamoyl moiety and the substituents in the meta position of the arene. Rate studies reveal a dominant disolvated-monomer-based orthometalation followed by a di- or trisolvated arylsodium monomer-based rearrangement. Kinetic evidence of a NaDA-catalyzed Snieckus-Fries rearrangement suggests the intermediacy of mixed trimers. Competitive halide eliminations to form benzyne are also discussed.
- Ma, Yun,Woltornist, Ryan A.,Algera, Russell F.,Collum, David B.
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p. 9051 - 9057
(2019/08/15)
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- Directed ortho-Metalation of O-Aryl N,N-Dialkylcarbamates: Methodology, Anionic ortho-Fries Rearrangement, and Lateral Metalation
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The directed ortho-lithiation reactions of O-aryl N,N-dialkylcarbamates as well as O-1-naphthyl and O-2-naphthyl N,N-dialkylcarbamates with sec-butyllithium/tetramethylethylenediamine (sBuLi/TMEDA) followed by quenching with various electrophiles afford a range of polysubstituted aromatic compounds. If the solutions of the ortho-lithiated carbamates are warmed to room temperature without the addition of external electrophiles, salicylamide and 1- and 2-hydroxynaphthamide derivatives are formed through anionic ortho-Fries rearrangements. The relative stabilities and reactivities of different O-aryl N,N-dialkylcarbamates were investigated. The lateral metalation of 2-tolyl carbamates with lithium diisopropylamide (LDA) provides a route to benzo[b]furan-2(3H)-ones. Previously reported results are used in a comparison of seven O-based directed metalation groups in reactions with several electrophiles. The described methodology is useful for the preparation of 1,2,3-substituted aromatic compounds.
- Miah, M. A. Jalil,Sibi, Mukund P.,Chattopadhyay,Familoni, Oluwole B.,Snieckus, Victor
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p. 440 - 446
(2017/12/15)
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- Direct Hydroxylation and Amination of Arenes via Deprotonative Cupration
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Deprotonative directed ortho cupration of aromatic/heteroaromatic C-H bond and subsequent oxidation with t-BuOOH furnished functionalized phenols in high yields with high regio- and chemoselectivity. DFT calculations revealed that this hydroxylation reaction proceeds via a copper (I → III → I) redox mechanism. Application of this reaction to aromatic C-H amination using BnONH2 efficiently afforded the corresponding primary anilines. These reactions show broad scope and good functional group compatibility. Catalytic versions of these transformations are also demonstrated.
- Tezuka, Noriyuki,Shimojo, Kohei,Hirano, Keiichi,Komagawa, Shinsuke,Yoshida, Kengo,Wang, Chao,Miyamoto, Kazunori,Saito, Tatsuo,Takita, Ryo,Uchiyama, Masanobu
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supporting information
p. 9166 - 9171
(2016/08/05)
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- Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing
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In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization.We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures.The microreactorwas applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production.
- Kim, Heejin,Min, Kyoung-Ik,Inoue, Keita,Im, Do Jin,Kim, Dong-Pyo,Yoshida, Jun-Ichi
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p. 691 - 694
(2016/05/19)
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- Copper-catalyzed cross dehydrogenative coupling of N,N-disubstituted formamides and phenols: A direct access to carbamates
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An efficient copper-catalyzed protocol has been developed for the synthesis of carbamates from dialkylformamides and phenols possessing directing groups such as benzothiazole, quinoline and formyl at the ortho-position. In this chelation assisted approach, C-O bond formation takes place via a cross dehydrogenative coupling (CDC) between the formyl C-H of dialkylformamide and phenolic O-H in the presence of copper(II)acetate/aqueous tertbutyl hydroperoxide. Under identical reaction conditions, salicylic acid derivatives underwent amidation with the carboxylic group rather than formamidation of the phenolic OH. The use of a cheap and environmentally benign catalyst along with the tolerance of a wide range of functional groups makes this an easy, phosgene-free route to carbamates. carbamates; C-H activation; copper catalysis; cross dehyrogenative coupling
- Ali, Wajid,Rout, Saroj K.,Guin, Srimanta,Modi, Anju,Banerjee, Arghya,Patel, Bhisma K.
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p. 515 - 522
(2015/03/05)
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- Lithiation of a silyl ether: Formation of an ortho-fries hydroxyketone
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A hydroxy-directed alkylation of an N,N-diethylarylamide using CIPE-assisted α-silyl carbanions (CIPE=complex-induced proximity effect) has been developed using a simple reagent combination of LDA (lithium diisopropylamide) and chlorosilane. A study of the mechanism, and the application of the procedure to an anionic Snieckus-Fries rearrangement for a highly efficient synthesis of the potent phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, are reported.
- Lo, Hong-Jay,Lin, Chin-Yin,Tseng, Mei-Chun,Chein, Rong-Jie
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p. 9026 - 9029
(2014/09/17)
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- Novel synthesis of a new surfactant 4-((4-bromophenyl)(dodecyl)amino)-4- oxobutanoic acid containing a benzene ring using a copper catalyst cross-coupling reaction and its properties
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A new surfactant 4-((4-bromophenyl)(dodecyl)amino)-4-oxobutanoic acid with a benzene spacer was synthesized via a novel copper catalyzed cross-coupling reaction. Its structure was confirmed by FTIR, 1H-NMR, 13C-NMR and HRMS; its purity was checked by HPLC. Dynamic light scattering and an atomic force microscope showed that it forms an unusual large-diameter premicellar aggregation below the CMC.
- Chen, Minggui,Hu, Xinqi,Fu, Meilong
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p. 581 - 585
(2013/07/26)
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- Ortho-and para-selective ruthenium-catalyzed C(sp2)-H oxygenations of phenol derivatives
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Versatile ruthenium catalysts allowed for efficient direct oxygenations of aryl carbamates under remarkably mild reaction conditions. In addition to chelation-assisted C-H activation, the optimized ruthenium catalyst proved amenable to para-selective hydroxylations of anisoles without Lewis basic directing groups.
- Liu, Weiping,Ackermann, Lutz
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supporting information
p. 3484 - 3486
(2013/07/26)
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- Ruthenium-catalyzed oxidative C(sp2)-H bond hydroxylation: Site-selective C-O bond formation on benzamides
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Well-defined ruthenium carboxylate complexes enabled unprecedented ruthenium-catalyzed C(sp2)-H hydroxylations on benzamides with PhI(OAc)2 as the oxidant at a remarkably low catalyst loading of 1.0 mol %.
- Thirunavukkarasu, Vedhagiri S.,Hubrich, Jonathan,Ackermann, Lutz
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supporting information; experimental part
p. 4210 - 4213
(2012/10/08)
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- Synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups
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Figure presented In this paper, a novel synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups is presented. Anionically activated trifluoromethyl groups react with secondary amines under aqueous conditions to afford tertiary amides. The mechanism involves initial elimination of hydrogen fluoride by an E1cB mechanism to afford an electrophilic quinone methide- or azafulvene-type intermediate that reacts with secondary amines under aqueous conditions to afford the tertiary amide in good yield (up to 99%).
- OMahony, Gavin,Pitts, Andrew K.
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supporting information; experimental part
p. 2024 - 2027
(2010/06/21)
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- Anionic ortho-fries rearrangement, a facile route to arenol-based mannich bases
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Phenol and 1-naphthol-based carbamates undergo the anionic ortho-Fries rearrangement to their corresponding amides. Bulky substitution at position 8 of 1-naphthol-based carbamates makes the rearrangement an exclusive reaction, even at -90 C, under a variety of conditions. The amides can be efficiently reduced to the corresponding Mannich bases. A novel route to 7-[(dialkylamino)methyl]-8- hydroxy-1-naphthaldehydes is presented.
- Assimomytis, Nikos,Sariyannis, Yiannis,Stavropoulos, Georgios,Tsoungas, Petros G.,Varvounis, George,Cordopatis, Paul
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experimental part
p. 2777 - 2782
(2010/03/03)
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- 1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES, PREPARATIONS THEREOF AND USES THEREOF
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Compounds of general formula (I) wherein D, E, R1, R2, R3, R4, R5, R6 and R7 are as defined in the specification, as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
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Page/Page column 45-46
(2008/06/13)
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- Hydroxylation of carbanions with lithium teri-butyl peroxide acting as an oxenoid
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The lithium salt of terf-butyl hydroperoxide can convert alkyl, vinyl, aryl carbanions, acetylides and various enolates into the corresponding hydroxylated derivatives in good yields and under mild conditions. Eisevier.
- Julia, Marc
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- BeCl2 as a new highly selective reagent for dealkylation of aryl-methyl ethers
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An efficient and simple method is introduced for the selective removal of methyl group from poly aryl-methyl ethers, in some important derivatives of benzophenones, xanthones, anthraquinones, aryl esters, benzamides and nitroanisoles with BeCl2.
- Sharghi, Hashem,Tamaddon, Fatemeh
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p. 13623 - 13640
(2007/10/03)
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- Directed ortho metalation of n,n-diethyl benzamides. Methodology and regiospecific synthesis of useful contiguously tri- and tetra-substituted oxygenated aromatics, phthalides and phthalic anhydrides
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Full experimental details for the directed ortho metalation approch to a variety of simple ortho-substituted N,N-diethyl benzamides (Table 1) and contiguously 1,2,3- and 1,2,3,4-substituted benzamides (Tables 2) are given. The efficient conversion of these benzamides (6, 10, 12, 13, 18, 19) into phthalides (9a-b, 16b-c, 17) and phthalic anhydrides (8,16a), compounds previously available by demanding, classical methods, is detailed. A short synthesis of iso-ochracinic acid (27) is described.
- De Silva,Reed,Billedeau,Wang,Norris,Snieckus
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p. 4863 - 4878
(2007/10/02)
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- Intramolecular General Base Catalysis and the Rate-determining Step in the Nucleophilic Cleavage of Ionized Phenyl Salicylate with Primary and Secondary Amines
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The nucleophilic second-order rate constants for the reactions of ionized phenyl salicylate (PS-) with primary and secondary amines have revealed Broensted plots of slopes βnuc1 = 0.52+/-0.06 and βnuc2 = 0.27+/-0.05, respectively.The suggested stepwise reaction mechanism involves the intramolecular proton transfer from cationic nitrogen to the anionic phenolic oxygen to form the monoanionic tetrahedral addition intermediate as the rate-determining step.The low value of βnuc2 is attributed to the extensive of proton transfer in the late transition state while the large value of βnuc1 is ascribed to the proton transfer in the early transition state of the rate-determining step.However, these low and high values of βnuc2 and βnuc1, respectively, are also compatible with the occurence of respective early and late transition states in the rate-determining step involving concerted intramolecular general base-catalysed nucleophilic attack at the carbonyl carbon of PS-.Significantly large positive deviations from Broensted plots have been observed for the reactivities of α-nucleophiles toward PS-.Monoprotonated ethane-1,2-diamine is ca. 20-fold more reactive than would be expected from its basicity, and this is attributed to the occurence of the intramolecular general acid catalysis.The reactions of PS- with hydroxylamine and N-methylhydroxylamine involve ca. >/=70 percent aminolysis and -.
- Khan, Mohammad Niyaz
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p. 199 - 208
(2007/10/02)
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- DIRECTED ORTHO METALATION OF SILYLOXYBENZAMIDES. ANION INDUCED O C SILICON REARRANGEMENT
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Trialkylsilyloxybenzamides 4, o- and m-OSiR3 undergo directed ortho metalation-mediated silicon rearrangement to salicylamides 6, 6- and 3-OH by intra- and inter-molecular mechanisms respectively.
- Billedeau, R.J.,Sibi, M.P.,Snieckus, V.
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p. 4515 - 4518
(2007/10/02)
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- The Directed Ortho Lithiation of O-Aryl Carbamates. An Anionic Equivalent of the Fries Rearrangement
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Ortho-Lithiated O-aryl carbamates 3 constitute new synthetic intermediates which by treatment with a variety of electrophiles lead to ortho-substituted carbamates 4 and by rearrangement provide salicylamides 6.
- Sibi, Mukund P.,Snieckus, Victor
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p. 1935 - 1937
(2007/10/02)
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- REACTION OF PHENOL WITH DIETHYLCARBAMOYL CHLORIDE IN THE PRESENCE OF LEWIS ACID
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In the presence of either SnCl4 or AlCl3, phenol reacts with diethylcarbamoyl chloride to give phenyl N,N-diethylcarbamate, which undergoes the Fries rearrangement at 170-180 deg C and is capable of being acylated by diethylcarbamoyl chloride in the para position.
- Isakova, A. P.,Naumov, Yu. A.,Nikeryasova, S. V.,Stepanova, A. A.
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p. 1115 - 1119
(2007/10/02)
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- The Tertiary Amide as an Effective Director of Ortho Lithiation
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The tertiary amides N,N-diethylbenzamide (1) and N,N-diisopropylbenzamide (3) give the ortho-lithiated species 2 on treatment with sec-BuLi/TMEDA or n-BuLi/TMEDA, respectively, at -78 deg.Lithiation of 1 followed by rection with either methyl iodide, ethyl iodide, benzophenone, acetone, benzaldehyde, or trimethoxyborane-hydrogen peroxide gives the expected ortho substituted product.Intramolecular competition between the diethyloamido and chloro, methoxyl, sulfonamido, (dimethylamino)methyl, or oxazolino functions in ortho- and para-substituted benzamides establishes the tertiary amido group to be more effective in directing metalation than any noncarboxamide functional group under the prescribed conditions.Complimentarity of directing effects is observed with the chloro and methoxyl groups in the meta-substituted diethylbenzamides but not with the methyl group.The secondary amide is found to have a directing ability comparable to the tertiary amide with sec-BuLi/TMEDA at -78 deg in THF although the yields are low. 13C NMR chemical shifts are particularly useful for the structural assignments which are confirmed chemically by lactonization of some products.A labeling study with N,N-diisopropyl-2,6-dideuteriobenzamide suggests that lithiation of the ortho position of 3 is direct and not the result of rearrangement of an initially formed α-aza anion.Control of metalation at the ortho or benzylic position by proper selection of the organolithium base is illustrated for N,N-diisopropyl-p-toluamide.The value of the tertiary amide for control of ortho lithiations and regiospecific aromatic substitutions is noted.
- Beak, Peter,Brown, Roger A.
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