- Facile Conversion of Molecularly Complex (Hetero)aryl Carboxylic Acids into Alkynes for Accelerated SAR Exploration
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1,2,3-Triazoles are well-established bioisosteres for amides, often installed as a result of structure?activity-relationship (SAR) exploration. A straightforward approach to assess the effect of the replacement of an amide by a triazole would start from the carboxylic acid and the amine used for the formation of a given amide and convert them into the corresponding alkyne and azide for cyclization by copper-catalyzed alkyne?azide cycloaddition (CuAAC). Herein, we report a functional-group-tolerant and operationally simple decarbonylative alkynylation that allows the conversion of complex (hetero)aryl carboxylic acids into alkynes. Furthermore, the utility of this method was demonstrated in the preparation of a triazolo analog of the commercial drug moclobemide. Lastly, mechanistic investigations using labeled carboxylic acid derivatives clearly show the decarbonylative nature of this transformation.
- Lutter, Ferdinand H.,Jouffroy, Matthieu
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supporting information
p. 14816 - 14820
(2021/10/08)
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- Decarbonylative Sonogashira Cross-Coupling of Carboxylic Acids
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Decarbonylative Sonogashira cross-coupling of carboxylic acids by palladium catalysis is presented. The carboxylic acid is activated in situ by the formation of a mixed anhydride and further decarbonylates using the Pd(OAc)2/Xantphos system to provide an aryl-Pd intermediate, which is intercepted by alkynes to access the traditional Pd(0)/(II) cycle using carboxylic acids as ubiquitous and orthogonal electrophilic cross-coupling partners. The methodology efficiently constructs new C(sp2)-C(sp) bonds and can be applied to the derivatization of pharmaceuticals. Mechanistic studies give support to decarbonylation preceding transmetalation in this process.
- Liu, Chengwei,Szostak, Michal
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supporting information
p. 4726 - 4730
(2021/06/28)
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- Nickel-Catalyzed Decarbonylative Alkynylation of Acyl Fluorides with Terminal Alkynes under Copper-Free Conditions
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Nickel-catalyzed decarbonylative alkynylation of acyl fluorides with terminal silylethynes under copper-free conditions is described. This newly developed method has a wide substrate scope, affording internal silylethynes in moderate to high yields. The formation of 1,3-diynes as homocoupled products and conjugate enones as carbonyl-retentive products were effectively suppressed.
- Chen, Qiang,Fu, Liyan,You, Jingwen,Nishihara, Yasushi
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supporting information
p. 1560 - 1564
(2020/11/12)
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- Catalytic Decarboxylation of Silyl Alkynoates to Alkynylsilanes
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Herein, we describe a decarboxylative approach to the preparation of alkynylsilanes. Treatment of a silyl alkynoate in N,N-dimethylformamide (DMF) at 80 °C in the presence of catalytic amounts of CuCl and PCy3 produced the corresponding alkynylsilane in excellent yield. The copper-catalyzed decarboxylation proceeded smoothly with low catalyst loadings (0.5 mol % of CuCl and 1.0 mol % of PCy3) under mild reaction conditions and is easily scalable to gram quantities.
- Aoyagi, Keiya,Choi, Jun-Chul,Kawatsu, Takahiro,Matsumoto, Kazuhiro,Nakajima, Yumiko,Sato, Kazuhiko
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- Sterically Controlled Late-Stage C-H Alkynylation of Arenes
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Phenylacetylenes are key structural motifs in organic chemistry, which find widespread applications in bioactive molecules, synthetic intermediates, functional materials, and reagents. These molecules are typically prepared from prefunctionalized starting materials, e.g. using the Sonogashira coupling, or using directing group-based C-H activation strategies. While highly efficient, these approaches remain limited by their inherent selectivities for specific regioisomers. Herein we present a complementary approach based on an arene-limited nondirected C-H activation. The reaction is predominantly controlled by steric rather than electronic factors and thereby gives access to a complementary product spectrum with respect to traditional methods. A broad scope as well as the suitability of this protocol for late-stage functionalization are demonstrated.
- Mondal, Arup,Chen, Hao,Fl?mig, Lea,Wedi, Philipp,Van Gemmeren, Manuel
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supporting information
p. 18662 - 18667
(2019/11/28)
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- Nickel-Catalyzed Decarboxylative C–Si Bond Formation: A Regioselective Cross-Coupling Between Trialkyl Silanes and α,β-Unsaturated Carboxylic Acids
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This report presents the first example of nickel-catalyzed mild decarboxylative cross-coupling reaction for the regioselective formation of C–Si bond. An easily accessible and significantly stable Ni (dmg)2 owes the role of key promoter. This r
- Allam, Bharat Kumar,Azeez, Sadaf,Kandasamy, Jeyakumar
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- Geometric E→Z Isomerisation of Alkenyl Silanes by Selective Energy Transfer Catalysis: Stereodivergent Synthesis of Triarylethylenes via a Formal anti-Metallometallation
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An efficient geometrical E→Z isomerisation of alkenyl silanes is disclosed via selective energy transfer using an inexpensive organic sensitiser. Characterised by operational simplicity, short reaction times (2 h), and broad substrate tolerance, the reaction displays high selectivity for trisubstituted systems (Z/E up to 95:5). In contrast to thermal activation, directionality results from deconjugation of the π-system in the Z-isomer due to A1,3-strain thereby inhibiting re-activation. The structural importance of the β-substituent logically prompted an investigation of mixed bis-nucleophiles (Si, Sn, B). These versatile linchpins also undergo facile isomerisation, thereby enabling a formal anti-metallometallation. Mechanistic interrogation, supported by a theoretical investigation, is disclosed together with application of the products to the stereospecific synthesis of biologically relevant target structures.
- Fa?bender, Svenja I.,Molloy, John J.,Mück-Lichtenfeld, Christian,Gilmour, Ryan
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supporting information
p. 18619 - 18626
(2019/11/16)
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- Et2Zn-mediated stoichiometric C(sp)-H silylation of 1-alkynes and chlorosilanes
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A first example of an Et2Zn mediated silylation of 1-aklynes is reported. A series of functional groups are tolerated in this reaction. Mechanistic studies support Zn alkynilides as intermediates in the reaction. This reaction protocol provides a practical method for the preparation of alkynylsilanes and expands the application of organometallic zinc in organic synthesis.
- Huang, Pan,Xu, Dawen,Reich, Robert M.,Kaiser, Felix,Liu, Boping,Kühn, Fritz E.
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supporting information
p. 1574 - 1577
(2019/05/17)
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- Diborative Reduction of Alkynes to 1,2-Diboryl-1,2-Dimetalloalkanes: Its Application for the Synthesis of Diverse 1,2-Bis(boronate)s
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Reduction of alkynes with alkali metals in the presence of B2pin2 results in diboration of alkynes. Distinct from conventional dissolving metal hydrogenations, two carbon-boron bonds and also two carbon-alkali metal bonds can be constructed in one operation to form 1,2-diboryl-1,2-dimetalloalkanes. The 1,2-diboryl-1,2-dimetalloalkanes generated are readily convertible to a wide range of vicinal bis(boronate)s. In particular, oxidation of the 1,2-dianionic species provides (E)-1,2-diborylalkenes, unique anti-selective diboration of alkynes being thus executed.
- Takahashi, Fumiya,Nogi, Keisuke,Sasamori, Takahiro,Yorimitsu, Hideki
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supporting information
p. 4739 - 4744
(2019/06/27)
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- Chemoselective Aerobic Cross-Dehydrogenative Coupling of Terminal Alkynes with Hydrosilanes by a Nanoporous Gold Catalyst
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Aerobic cross-dehydrogenative coupling between terminal alkynes and hydrosilanes occurred in the presence of nanoporous gold catalyst under O2 atmosphere. A variety of alkynylsilanes were synthesized in good-to-high yields and the catalyst was easily recovered and reused many times. Furthermore, the chemoselective direct silyl protection of terminal acetylenes of alkynols over the hydroxyl groups was achieved with this catalytic system.
- Kavthe, Rahul D.,Ishikawa, Yoshifumi,Kusuma, Indra,Asao, Naoki
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supporting information
p. 15777 - 15780
(2018/10/09)
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- Trimethylsilyl-Protected Alkynes as Selective Cross-Coupling Partners in Titanium-Catalyzed [2+2+1] Pyrrole Synthesis
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Trimethylsilyl (TMS)-protected alkynes served as selective alkyne cross-coupling partners in titanium-catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS-protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido comple
- Chiu, Hsin-Chun,Tonks, Ian A.
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supporting information
p. 6090 - 6094
(2018/05/30)
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- Amide to Alkyne Interconversion via a Nickel/Copper-Catalyzed Deamidative Cross-Coupling of Aryl and Alkenyl Amides
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A nickel-catalyzed deamidative cross-coupling reaction of amides with terminal alkynes as coupling partners was disclosed. This newly developed methodology allows the direct interconversion of amides to alkynes and enables a facile route for C(sp2)-C(sp) bond formation in a straightforward and mild fashion.
- Srimontree, Watchara,Chatupheeraphat, Adisak,Liao, Hsuan-Hung,Rueping, Magnus
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p. 3091 - 3094
(2017/06/23)
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- PALLADIUM COMPLEX, COUPLING REACTION USING THE PALLADIUM COMPLEX AND METHOD FOR PRODUCING ORGANIC ALKYNE COMPOUND USING THE COUPLING REACTION
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PROBLEM TO BE SOLVED: To provide a novel palladium catalyst which can be used for synthesis of an organic alkyne compound, using an arylation agent having an ester group in place of halogenated aryl. SOLUTION: The present invention provides a palladium co
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Paragraph 0189-0191
(2017/10/31)
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- Cyclopropenation of internal alkynylsilanes and diazoacetates catalyzed by copper(i) N-heterocyclic carbene complexes
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Copper(i) N-heterocyclic carbene (CuNHC) complexes are more catalytically active than traditional transition metal salts for the cyclopropenation of internal alkynylsilanes and diazoacetate compounds. A series of 1,2,3-trisubstituted and 1,2,3,3-tetrasubstituted cyclopropenylsilane compounds were isolated in good overall yields. An interesting regioselective and chemodivergent reaction pathway was also observed to furnish a tetra-substituted furan for an electron-rich donor/acceptor diazoacetate. Finally, a practical synthesis of a cyclopropenyl-containing starting material that is useful for bioorthogonal chemistry is also described.
- Thomas, Thomas J.,Merritt, Benjamin A.,Lemma, Betsegaw E.,McKoy, Adina M.,Nguyen, Tri,Swenson, Andrew K.,Mills, Jeffrey L.,Coleman, Michael G.
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supporting information
p. 1742 - 1747
(2016/02/10)
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- A novel synthesis of polysubstituted chromenes from various salicylaldehydes and alkynes under mild conditions
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A novel synthesis of poly substituted chromenes from various salicylaldehydes and alkynes not having electron withdrawing substituents under mild conditions has been developed. The procedure is applicable for easily available various substituted salicylal
- Tanaka, Kenta,Hoshino, Yujiro,Honda, Kiyoshi
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supporting information
p. 2448 - 2450
(2016/05/19)
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- Nickel-catalyzed alkynylation of anisoles via C-O bond cleavage
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A new cross-coupling reaction has been developed for the introduction of an alkyne moiety to an anisole derivative through C-O bond activation using an NHC ligand. This method has been used for direct alkynylation of a broad range of anisole derivatives a
- Tobisu, Mamoru,Takahira, Tsuyoshi,Ohtsuki, Akimichi,Chatani, Naoto
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supporting information
p. 680 - 683
(2015/03/05)
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- Enantioselective synthesis of α-aminosilanes by copper-catalyzed hydroamination of vinylsilanes
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The synthesis of α-aminosilanes by a highly enantio- and regioselective copper-catalyzed hydroamination of vinylsilanes is reported. The system employs Cu-DTBM-SEGPHOS as the catalyst, diethoxymethylsilane as the stoichiometric reductant, and O-benzoylhyd
- Niljianskul, Nootaree,Zhu, Shaolin,Buchwald, Stephen L.
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p. 1638 - 1641
(2015/02/05)
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- Synthesis of Multinuclear Copper Complexes Bridged by Diquinolylamidinates and Their Application to Copper-Catalyzed Coupling of Terminal Alkynes and Aryl, Allyl, and Benzyl Halides
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A dinuclear copper complex containing N,N′-diquinolylformamidinate and a tetranuclear copper complex containing N,N′-diquinolylacetamidinate were synthesized. The structure of complexes was confirmed by X-ray analysis, showing that copper atoms were bridg
- Nakane, Takayuki,Tanioka, Yuta,Tsukada, Naofumi
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p. 1191 - 1196
(2015/04/27)
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- Rapid synthesis of crowded aromatic architectures from silyl acetylenes
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Congested aromatic systems were prepared by benzannulating silyl-protected arylacetylenes. The silyl groups may be retained in the naphthalene products and transformed into iodides in high yield. The desirable attributes of this strategy, particularly its remarkable tolerance of sterically hindered alkynes, are showcased in the efficient synthesis of a congested, branched oligo(naphthalene). As such, benzannulations of diaryl and silyl-protected acetylenes show outstanding promise for accessing new aromatic architectures.
- Hein, Samuel J.,Arslan, Hasan,Keresztes, Ivan,Dichtel, William R.
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supporting information
p. 4416 - 4419
(2015/01/08)
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- Heterogeneously catalyzed aerobic cross-dehydrogenative coupling of terminal alkynes and monohydrosilanes by gold supported on oms-2
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Cross-dehydrogenative coupling of various terminal alkynes and monohydrosilanes efficiently proceeded in the presence of gold supported on OMS-2 (Au/OMS-2) using O2 as a terminal oxidant, affording the corresponding alkynylsilanes in moderate to high yields (see picture). The observed catalysis was truly heterogeneous, and the catalyst could be reused at least ten times without a significant loss of its high catalytic performance. Copyright
- Yamaguchi, Kazuya,Wang, Ye,Oishi, Takamichi,Kuroda, Yoshiyuki,Mizuno, Noritaka
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supporting information
p. 5627 - 5630
(2013/06/27)
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- Arylsulfonylacetylenes as alkynylating reagents
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The unexpected anti-Michael addition of RLi to β-substituted sulfonylacetylenes, followed by in situ elimination of the ion sulfinate, allows the alkynylation of C(sp2) and C(sp3). Aryl and heteroaryl acetylenes, enynes, and mono and dialkyl alkynes can be obtained in very high yields under very mild conditions, avoiding the use of transition metals as catalysts and, in many cases, haloderivatives as starting materials. Furthermore, the use of lithium 2-p-tolylsulfinyl benzylcarbanions as nucleophiles of these reactions allows their stereocontrolled alkynylation, affording enantiomerically pure alkynes or enantioenriched allenes depending on the protonating agent (NH4Cl or H2O).
- Marzo, Leyre,Aleman, Jose,Garcia Ruano, Jose Luis
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p. 403 - 407
(2013/07/26)
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- Expanding the scope of arylsulfonylacetylenes as alkynylating reagents and mechanistic insights in the formation of Csp2-Csp and Csp 3-Csp bonds from organolithiums
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We describe the unexpected behavior of the arylsulfonylacetylenes, which suffer an "anti-Michael" addition of organolithiums producing their alkynylation under very mild conditions. The broad scope, excellent yields, and simplicity of the experimental procedure are the main features of this methodology. A rational explanation of all these results can be achieved by theoretical calculations, which suggest that the association of the organolithiums to the electrophile is a previous step of their intramolecular attack and is responsible for the unexpected "anti-Michael" reactions observed for substituted sulfonylacetylenes. A calculated conclusion: A new transition-metal-free strategy for the synthesis of any kind of alkynyl derivatives in high yields in the reaction of organolithium species with arylsulfonylacetylenes is presented (see scheme). Theoretical calculations provide a rational explanation and suggest that association of the organolithium to the electrophile is a previous step of their intramolecular attack and is responsible for the "anti-Michael" reaction. Copyright
- Garcia Ruano, Jose Luis,Aleman, Jose,Marzo, Leyre,Alvarado, Cuauhtemoc,Tortosa, Mariola,Diaz-Tendero, Sergio,Fraile, Alberto
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supporting information; experimental part
p. 8414 - 8422
(2012/07/27)
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- Transition-metal-free alkynylation of aryl chlorides
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Two sets of conditions have been developed for a base-mediated, transition-metal-free alkynylation of aryl chlorides that proceeds via benzyne intermediates. The first set of conditions involves the use of TMPLi base in a pentane/THF mixture at 25 °C. The
- Truong, Thanh,Daugulis, Olafs
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supporting information; experimental part
p. 4172 - 4175
(2011/10/02)
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- Iron-catalyzed cross-coupling between 1-bromoalkynes and grignard-derived organocuprate reagents
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An efficient iron-catalyzed cross-coupling reaction between alkynyl bromides and Grignard-derived organocuprates has been developed. A series of alkynylarenes were successfully synthesised by starting from different 1-bromoalkynes and Grignard reagents. The methodology was successfully used for the two-step stereoselective synthesis of combretastatins and represents a valid alternative to the classical syntheses of alkynylarenes.
- Castagnolo, Daniele,Botta, Maurizio
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supporting information; experimental part
p. 3224 - 3228
(2010/08/20)
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- A practical heterogeneous catalyst for the suzuki, sonogashira, and stille coupling reactions of unreactive aryl chlorides
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(Chemical Equation Present) Practical catalyst: A magnetic nanoparticle-supported palladium catalyst was developed for the highly efficient heterogeneous Suzuki, Sonogashira, and Stille couplings of a wide variety of aryl chlorides. Furthermore, the catalyst could be recycled by facile magnetic separation without any loss of activity.
- Jin, Myung-Jong,Lee, Dong-Hwan
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supporting information; experimental part
p. 1119 - 1122
(2010/05/17)
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- Phosphine-free Sonogashira coupling: reactions of aryl halides catalysed by palladium(II) complexes of azetidine-derived polyamines under mild conditions
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Readily synthesised, water-stable pyridylazetidine-based Pd(II) complexes have been studied as catalysts for the Sonogashira coupling reaction. Under low catalyst loadings, various aryl bromides and chlorides were efficiently coupled with phenylacetylene
- Lee, Dong-Hwan,Lee, Young Hoon,Harrowfield, Jack M.,Lee, Ik-Mo,Lee, Hong In,Lim, Woo Taik,Kim, Yang,Jin, Myung-Jong
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experimental part
p. 1630 - 1634
(2009/05/09)
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- Convenient copper- and solvent-free Sonogashira-type alkynylation of aryl iodides and bromides using Pd EnCat
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A straightforward methodology is described for the copper- and solvent-free alkynylations of aryl iodides and bromides using 0.1-0.01 mol % of Pd as Pd EnCat 40 or TPP30. High yielding reactions can be achieved under aerobic conditions for a variety of activated and deactivated aryl iodides; a few examples with aryl bromides are also described. Microwave irradiation is able to enhance yields and rates of these reactions.
- Carpita, Adriano,Ribecai, Arianna
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scheme or table
p. 204 - 207
(2009/04/19)
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- Efficient sonogashira coupling reaction catalyzed by palladium(II) β-oxoiminatophosphane complexes under mild conditions
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Palladium(II) β-oxoiminatophosphane complexes were used as catalysts for the Sonogashira coupling reaction. In the presence of very low amounts of the complexes, various aryl iodides and bromides were efficiently coupled with phenylacetylene even at room
- Lee, Dong-Hwan,Qiu, Huili,Cho, Min-Ho,Lee, Ik-Mo,Jin, Myung-Jong
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body text
p. 1657 - 1660
(2009/05/30)
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- Efficient copper-free Sonogashira coupling of aryl chlorides with palladium on charcoal
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Palladium on charcoal serves as an efficient and reusable solid supported catalyst for the Sonogashira coupling of aryl chlorides with terminal acetylenes in the presence of a bulky, electron-rich biphenyl type ligand (XPhos), without copper co-catalyst. The Royal Society of Chemistry.
- Komáromi, Anna,Novák, Zoltán
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supporting information; experimental part
p. 4968 - 4970
(2009/06/05)
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- Tetraarylphosphonium halides as arylating reagents in Pd-catalyzed heck and cross-coupling reactions
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(Chemical Equation Presented) Highly efficient: Tetraarylphosphonium halides, Ar4P+X-, as arylating reagents efficiently deliver an aryl group in Pd-catalyzed reactions with olefins, organoboron compounds, and terminal alkynes (see scheme).
- Hwang, Lee Kyoung,Na, Youngim,Lee, Junseong,Do, Youngkyu,Chang, Sukbok
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p. 6166 - 6169
(2007/10/03)
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- A versatile catalyst for the sonogashira coupling of aryl chlorides
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Aryl chlorides are suitable substrates for the Sonogashira coupling! By using the versatile catalyst system Na2[PdCl4]/PR3/ Cul (PR3= (1-Ad)2PBn, PtBu3), the Sonogashira coupling [Eq. (a)] of aryl chlorides with alkynes generates excellent yields of the corresponding disubstituted aryl alkynes.
- Koellhofer, Axel,Pullmann, Thomas,Plenio, Herbert
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p. 1056 - 1058
(2007/10/03)
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- Highly reactive trialkylsilylation reagents derived from bis(trifluoromethanesulfonyl)imide - Silylation of functional groups, alkines and reactive aromatics
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The synthesis of trialkylsilyl-bis(trifluormethanesulfonyl)imides 3 is described. Compounds 3 with bulky trialkylsilyl groups 3a,b only exist in the silatautomeric form 3a′,b′ under usual conditions, 3c in the N-trimethylsilyl structure. Despite of the bulky silyl substituents in 3a′,b′ their reactivity is higher than that of trimethylsilyltriflate. Alcohols, carbonyl compounds, nitroalkanes and carboxylic acid esters are silylated in good yields, especially by the more reactive triisopropylsilyl derivative 3b′ in presence of tertiary amines, tert.-Butyl carboxylates and benzylcarboxylates are cleaved. Monosubstituted alkines and electron-rich (hetero) aromatics are carbosilylated in presence of N-ethyl-diisopropylamine.
- Simchen, Gerhard,Jonas, Simon
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experimental part
p. 506 - 512
(2011/10/17)
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