- Barbier-type reactions of aryl halides with ketones mediated by Samarium diiodide
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Barbier-type reaction of aryl halides with ketones took place on treatment with samarium diiodide in benzene containing 10% hexamethylphosphoric triamide (HMPA). The reaction involves an aryl samarium as an intermediate.
- Kunishima,Hioki,Kono,Sakuma,Tani
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- A Fast and General Route to Ketones from Amides and Organolithium Compounds under Aerobic Conditions: Synthetic and Mechanistic Aspects
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We report that the nucleophilic acyl substitution reaction of aliphatic and (hetero)aromatic amides by organolithium reagents proceeds quickly (20 s reaction time), efficiently, and chemoselectively with a broad substrate scope in the environmentally responsible cyclopentyl methyl ether, at ambient temperature and under air, to provide ketones in up to 93 % yield with an effective suppression of the notorious over-addition reaction. Detailed DFT calculations and NMR investigations support the experimental results. The described methodology was proven to be amenable to scale-up and recyclability protocols. Contrasting classical procedures carried out under inert atmospheres, this work lays the foundation for a profound paradigm shift of the reactivity of carboxylic acid amides with organolithiums, with ketones being straightforwardly obtained by simply combining the reagents under aerobic conditions and with no need of using previously modified or pre-activated amides, as recommended.
- Ghinato, Simone,Territo, Davide,Maranzana, Andrea,Capriati, Vito,Blangetti, Marco,Prandi, Cristina
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supporting information
p. 2868 - 2874
(2021/01/21)
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- Expeditious and practical synthesis of tertiary alcohols from esters enabled by highly polarized organometallic compounds under aerobic conditions in Deep Eutectic Solvents or bulk water
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An efficient protocol was developed for the synthesis of tertiary alcohols via nucleophilic addition of organometallic compounds of s-block elements (Grignard and organolithium reagents) to esters performed in the biodegradable choline chloride/urea eutectic mixture or in water. This approach displays a broad substrate scope, with the addition reaction proceeding quickly (20 s reaction time) and cleanly, at ambient temperature and under air, straightforwardly furnishing the expected tertiary alcohols in yields of up to 98%. The practicability of the method is exemplified by the sustainable synthesis of some representative S-trityl-L-cysteine derivatives, which are a potent class of Eg5 inhibitors, also via telescoped one-pot processes.
- Quivelli, Andrea F.,D'Addato, Giovanna,Vitale, Paola,García-álvarez, Joaquín,Perna, Filippo M.,Capriati, Vito
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- Ultrafast amidation of esters using lithium amides under aerobic ambient temperature conditions in sustainable solvents
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Lithium amides constitute one of the most commonly used classes of reagents in synthetic chemistry. However, despite having many applications, their use is handicapped by the requirement of low temperatures, in order to control their reactivity, as well as the need for dry organic solvents and protective inert atmosphere protocols to prevent their fast decomposition. Advancing the development of air- and moisture-compatible polar organometallic chemistry, the chemoselective and ultrafast amidation of esters mediated by lithium amides is reported. Establishing a novel sustainable access to carboxamides, this has been accomplished via direct C-O bond cleavage of a range of esters using glycerol or 2-MeTHF as a solvent, in air. High yields and good selectivity are observed while operating at ambient temperature, without the need for transition-metal mediation, and the protocol extends to transamidation processes. Pre-coordination of the organic substrate to the reactive lithium amide as a key step in the amidation processes has been assessed, enabling the structural elucidation of the coordination adduct [{Li(NPh2)(OCPh(NMe2))}2] (8) when toluene is employed as a solvent. No evidence for formation of a complex of this type has been found when using donor THF as a solvent. Structural and spectroscopic insights into the constitution of selected lithium amides in 2-MeTHF are provided that support the involvement of small kinetically activated aggregates that can react rapidly with the organic substrates, favouring the C-O bond cleavage/C-N bond formation processes over competing hydrolysis/degradation of the lithium amides by moisture or air.
- Bole, Leonie J.,Fairley, Michael,García-Alvarez, Joaquín,Hevia, Eva,Kennedy, Alan R.,Main, Laura,Mulks, Florian F.,O'Hara, Charles T.
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p. 6500 - 6509
(2020/07/15)
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- Directed: Ortho-metalation-nucleophilic acyl substitution strategies in deep eutectic solvents: The organolithium base dictates the chemoselectivity
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Directed ortho metalation (DoM) or nucleophilic acyl substitution (SNAc) can be efficiently programmed on the same aromatic carboxylic acid amide, in a choline chloride-based eutectic mixture, by simply switching the nature of the organolithium reagent. Telescoped, one-pot ortho-lithiation/Suzuki-Miyaura cross-couplings have also been demonstrated for the first time in Deep Eutectic Solvents.
- Ghinato, Simone,Dilauro, Giuseppe,Perna, Filippo Maria,Capriati, Vito,Blangetti, Marco,Prandi, Cristina
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p. 7741 - 7744
(2019/07/12)
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- Synthesis of Functionalized Ketones from Acid Chlorides and Organolithiums by Extremely Fast Micromixing
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Synthesis of ketones containing various functional groups from acid chlorides bearing electrophilic functional groups and functionalized organolithiums was achieved using a flow microreactor system. Extremely fast mixing is important for high chemoselectivity.
- Nagaki, Aiichiro,Sasatsuki, Kengo,Ishiuchi, Satoshi,Miuchi, Nobuyuki,Takumi, Masahiro,Yoshida, Jun-ichi
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supporting information
p. 4946 - 4950
(2019/03/21)
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- Reactions of organoboranes with carbanions bearing three potential leaving groups: unusual processes, products and mechanisms
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Known reagents that transfer three alkyl groups of a trialkylborane intramolecularly to a single carbon atom lack features to influence stereochemistry. We have investigated four reagents of type LiCCl2X, where X might be amenable to variation. All behaved differently. With X=OR (R=cyclohexyl, menthyl), the reagent decomposed, leading to only low yields of triple migration products. With X=S(O)Ph, a single migration occurred, followed by isomerisation to boron enolate-like species that hydrolysed to α-chloroalkyl phenyl sulfoxides or reacted with aldehydes to aldol-like products. With X=SO2Ph, the major product was the corresponding α,α-dichloroalkyl phenyl sulfone, apparently formed through a redox reaction. With X=S(O)(NMe)Ph, products of three intramolecular alkyl migrations were obtained with unhindered trialkylboranes. Attempts have been made to gain understanding of the sulfoxide process by investigating proportions of aldol-like products, using X-ray crystallography and ab initio calculations.
- Saleh, Basil A.,Smith, Keith,Elliott, Mark C.,Jones, D. Heulyn,Kariuki, Benson M.,El Hiti, Gamal A.
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p. 6914 - 6928
(2016/10/14)
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- Continuous flow synthesis of ketones from carbon dioxide and organolithium or grignard reagents
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We describe an efficient continuous flow synthesis of ketones from CO 2 and organolithium or Grignard reagents that exhibits significant advantages over conventional batch conditions in suppressing undesired symmetric ketone and tertiary alcohol byproducts. We observed an unprecedented solvent-dependence of the organolithium reactivity, the key factor in governing selectivity during the flow process. A facile, telescoped three-step-one-flow process for the preparation of ketones in a modular fashion through the in-line generation of organometallic reagents is also established.
- Wu, Jie,Yang, Xiaoqing,He, Zhi,Mao, Xianwen,Hatton, T. Alan,Jamison, Timothy F.
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supporting information
p. 8416 - 8420
(2014/08/18)
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- The convenient and useful esterification of bulky tertiary alcohols using strontium compounds
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Various esters reacted with metallic strontium and alkyl iodides to give dialkylated products, followed by adding acid chlorides or acid anhydrides to afford the corresponding bulky tert-alcohol esters in good yields.
- Miyoshi, Norikazu,Asaoka, Masashi,Miyazaki, Yasuaki,Tajima, Takahiro,Kikuchi, Makoto,Wada, Makoto
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supporting information; experimental part
p. 35 - 36
(2012/03/13)
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- Novel alkylidenating agents of iron(III) derivatives by base-mediated α,μ-dehydrohalogenation and their chemical trapping by cycloaddition
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Studies of the reactions between group 4 metal, chlorides (M = Ti, Zr, Hf) and methyllithium at -78 °C in toluene can lead to methylidene-metal complexes, H2C=MCl2, by a sequence of monomethylation, α-carbon lithiation and α,μ-elimination of LiCl. Here study of the preparation of alkylidene derivatives of iron was attempted by the interaction of FeCl3 with n-butyllithium in various ratios at -78 °C. The presence of any resulting butylidene-iron(III) derivative, nPrCH=FeE (E = Cl, nBu), was probed by adding chemical trapping agents, such as diphenylacetylene, benzonitrile, methyl benzoate and benzophenone. In each experiment the hydrolyzed products were consistent with a cycloaddition reaction of nPrCH=FeE with the trapping agent. The products from, di-phenylacetylene and from, benzonitrile with D2O workup are uniquely in accord with such a carbene precursor. A 3:1 ratio of nBuLi/FeCl3 gave the optimal yield of nPrCH=FenBu, ca. 80%, from, the MBu2FeCl precursor. When a 3:1. reaction mixture was simply brought to 25 °C and hydrolyzed, the purple alkylidene-iron complex decomposed completely to iron metal. A study of a 3:1 interaction of PhCH2MgCl and FeCl3 under similar conditions and trapping with diphenylacetylene provided evidence for the formation of PhCH=FeCH2Ph in ca. 40%. These results support; the hope that alkylidene-iron(III) analogs of the Grubbs reagents may be accessible by this process.
- Eisch, John J.,Sohn, Jane U.,Rabinowitz, Edon J.
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experimental part
p. 2971 - 2977
(2010/08/20)
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- The chemistry of alkylstrontium halide analogues, Part 2: Barbier-type dialkylation of esters with alkyl halides
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The chemistry of an alkylstrontium halide analogue was examined. In the presence of metallic strontium, the Barbier-type alkylation of esters with alkyl iodides proceeded smoothly at room temperature, under argon, to afford the corresponding dialkylated alcohols in good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Miyoshi, Norikazu,Matsuo, Tsuyoshi,Wada, Makoto
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p. 4253 - 4255
(2007/10/03)
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- The reaction of n-butyllithium with benzoic acid: Is nucleophilic addition competitive with deprotonation?
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An evaluation of a branching vs sequential mechanism for the reaction of benzoic acid with n-butyllithium favors the latter.
- Beak, Peter,Pfeifer, Lance A.
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p. 537 - 541
(2007/10/03)
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- Preparation and reactions of samarium diiodide in nitriles
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Samarium diiodide can be prepared from samarium metal in various nitriles. Because of its chemical inertness pivalonitrile is the most suitable solvent. Organic reactions mediated by SmI2 are slower than in THF, but selectivities are often improved. Reactions are greatly accelerated by addition of catalytic amounts of some transition metal salts.
- Hamann, Beatrice,Namy, Jean-Louis,Kagan, Henri B.
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p. 14225 - 14234
(2007/10/03)
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- The Sonochemical Barbier Reaction applied to Carboxylates. Study of a Model Case
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Sonication of a n-butyl halide, lithium benzoate and lithium metal in THF at room temperature provides the expected ketone and/or benzil in yields depending on the nature of the halogen.
- Danhui, Yang,Einhorn, Jacques,Einhorn, Cathy,Aurell, M. Jose,Luche, Jean-Louis
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p. 1815 - 1816
(2007/10/02)
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- The Geometry of the Carbanionic Moiety Influences the Non-Induced Diastereoselectivity of the -Wittig Rearrangement of Lithiated Diallyl Ethers
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Lithiated diallyl ethers with cis- or trans-configuration of the anionic moiety were generated from the diallyl ethers 10, from the vinylogous O,S-acetals 13, and from the O,S-acetals 14 by treatment with nBuLi (in the case of 10) or with lithium naphthal
- Goeppel, Dirk,Muenster, Ingo,Brueckner, Reinhard
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p. 3687 - 3708
(2007/10/02)
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- Nucleophilic properties of butyllithium versus free carboxylic acids
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In opposition to the generally accepted idea, butyl lithium is not only a deprotonating agent for free carboxylic acids, but can also act as a nucleophile on the carbon oxygen double bond.
- Einhorn,Einhorn,Luche
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p. 2771 - 2774
(2007/10/02)
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- X-ray Studies of Sterically Congested Diphenylethane Derivatives. Substitutent Effect on Carbon-Carbon Bond Length
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Crystal structures of several sterically strained diphenylethane derivatives have been obtained.The central C-C bond lengths in these compounds span 1.623 (7) to 1.649 (4) Angstroem but are independent of substitution on the phenyl ring.
- Maslak, Przemyslaw,Narvaez, Javier N.,Parvez, Masood
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p. 602 - 607
(2007/10/02)
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- Electron-transfer Reduction of Esters with Carbanions mediated by an Iron-Sulphur Cluster
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The iron-sulphur cluster (1) acts as an electron-transfer agent in the reduction of S-phenyl thiobenzoate and phenyl benzoate with n-butyl-lithium and phenyl-lithium to give benzil and benzoin.
- Inoue, Hiroo,Nagata, Tadashi
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p. 1177 - 1178
(2007/10/02)
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- EVIDENCE FOR SINGLE ELECTRON TRANSFER IN THE REACTIONS OF ORGANOMETALLIC COMPOUNDS WITH 2,3,3-TRIMETHYL-2-BUTYL PEROXYBENZOATE
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Utilization of a triptoxy radical probe in the reactions of organometallic compounds with 2,3,3-trimethyl-2-butyl peroxybenzoate indicates that the radical character of the reaction decreases in the order n-BuLi>n-BuMgCl>PhMgBr.
- Hendrickson, W. H.,MacDonald, W. D.,Howard, S. T.,Coligado, E. J.
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p. 2939 - 2942
(2007/10/02)
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- ONE-STEP SYNTHESIS OF KETONES FROM CARBOXYLIC ACIDS AND GRIGNARD REAGENTS IN THE PRESENCE OF A NICKEL(II)-PHOSPHINE CATALYST.
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A one-step synthesis of diaryl and alkyl-aryl ketones by the reaction of carboxylic acid with Grignard reagents in the presence of NiCl2(Ph2PCH2CH2PPh2) as catalyst is described.In the nickel-catalyzed Grignard reaction the formation of alcohols is nearly completely suppressed.
- Fiandanese, V.,Marchese, G.,Ronzini, L.
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p. 3677 - 3680
(2007/10/02)
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- CONVERSION OF PRIMARY AMIDES INTO ACTIVE ACYLATING AGENTS VIA ACYLPYRROLES.
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Several primary amides were converted to N-acylpyrroles on reaction with 1,4-dichloro-1,4-dimethoxybutane (1) and Amberlyst A-21 resin.The acylpyrroles act as active acylating agents.
- Lee, S.D.,Brook, Michael A.,Chan, T.H.
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p. 1569 - 1572
(2007/10/02)
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- Thermolabile Hydrocarbons, XX. Synthesis, Structure, and Strain of Sym. Tetraalkyl-1,2-diarylethanes
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The syntheses of 18 1,1,2,2-tetraalkyl-1,2-diarylethanes 1 - 4 by dimerisation procedures starting with 10 - 13 are reported.In the absence of p-substituents X and with increasing alkyl side chains the α,p-dimers 6 or their aromatic counter parts 7 are obtained besides or instead of 1.The relationships between strain enthalpy Hs, bond lengths, bond angles, torsional angles, and rotational barrier are discussed on the basis of force field calculations.They are supported by two additional experimental structure determinations by X-ray diffraction.
- Kratt, Guenter,Beckhaus, Hans-Dieter,Lindner, Hans Joerg,Ruechardt, Christoph
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p. 3235 - 3263
(2007/10/02)
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- Effets de cryptands et activation de bases. VI. Reactions d'organo-lithiens.
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Utilization of the cryptand shows the need of electrophilic catalysis by the Li(1+) ion in the nucleophilic addition of organolithium compounds to ketones, esters, or carboxylic acids.When nucleophilic addition is inhibited, organolithium reagents enolyze ketones or esters.When activated by cryptation of Li(1+), organolithium reagents attack ethers in a few minutes.With alkyl halides, only elimination takes place: exchange and nucleophilic substitution are not observed any longer in the presence of the cryptand.Generally speaking, the cryptand seems to enhance the basicity of the organolithium reagent, and nucleophilicity does not manifest itself any more.
- Perraud, Robert,Handel, Henri,Pierre, Jean-Louis
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p. 283 - 288
(2007/10/02)
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