- Synthesis of cyclic polyelectrolyte via direct copper(I)-catalyzed click cyclization
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Well-defined cyclic poly(acrylic acid) (PAA) has been successfully prepared based on the direct click cyclization. The linear poly(tert-butyl acrylate) (PtBA) with azide and TMS-protected alkyne group forms cyclic chain directly by the copper(I)-catalyzed click cyclization without any deprotection steps. Cyclic PAA is synthesized by the hydrolysis of cyclic PtBA. The present synthetic strategy provides a simple and efficient method to synthesize cyclic polyelectrolyte and can be applied to other polymer systems. Copyright
- Chen, Fenggui,Liu, Guangming,Zhang, Guangzhao
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- DICOBALTOCTACARBONYL-ALKYNE COMPLEXES AS INTERMEDIATES IN THE SYNTHESIS OF BICYCLOOCTENONES FOR THE SYNTHESIS OF CORIOLIN AND HIRSUTIC ACID
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Treatment of the readily prepared enzynes 12, 21 and 45 with Co2(CO)8 at ca 110 deg C results in high yields (80percent) of substituted bicyclooctenones, that are suitable for straightforward elaboration into coriolin and hirsutic acid precursors.A mechanistic hypothesis to explain the observed stereospecificity is presented.
- Magnus, Philip,Exon, Christopher,Albaugh-Robertson, Pamela
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- Silver-catalyzed heterocyclization: First total synthesis of the naturally occurring cis 2-hexadecyl-3-hydroxy-4-methylene butyrolactone
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The title compound was obtained in 4 steps with an overall yield of 64% with the silver-catalyzed cyclization of the corresponding substituted β-hydroxy-γ-acetylenic acid as the key step.
- Dalla,Pale
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- An unusual rearrangement of 1-trimethylsiloxy-3-bromomagnesium-2-propyne
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3-Trimethylsilyl-2-propyn-1-ol (4) was synthesized via the rearrangement of 1-trimethylsiloxy-3-bromomagnesium-2-propyne and followed by hydrolysis of the latter. The yield of compound 4 depends largely on the solvent used.
- Medvedeva,Novokshonov,Demina,Voronkov
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- Skeletal Optimization of Cytotoxic Lipidic Dialkynylcarbinols
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In line with a recent study of the pharmacological potential of bioinspired synthetic acetylenic lipids, after identification of the terminal dialkynylcarbinol (DAC) and butadiynyl alkynylcarbinol (BAC) moieties as functional antitumor pharmacophoric units, this work specifically addresses the issue of carbon backbone length. A systematic variation of the aliphatic chain length was thus carried out in both the DAC and BAC series. The critical impact of the length of the lipidic skeleton was first confirmed in the racemic series, with the highest cytotoxic activity observed for C17 to C18 backbones. Enantiomerically enriched samples were prepared by asymmetric synthesis of the optimal C18 DAC and C17 BAC derivatives. Samples with upgraded enantiomeric purity were alternatively produced by enzymatic kinetic resolution. Eutomers possessing the S configuration displayed cytotoxicity IC50 values as low as 15 nm against HCT116 cancer cells, the highest level of activity reached to date in this series.
- Bourkhis, Maroua,Gaspard, Hafida,Rullière, Pauline,de Almeida, Diana K. C.,Listunov, Dymytrii,Joly, Etienne,Abderrahim, Raoudha,de Mattos, Marcos C.,de Oliveira, Maria C. F.,Maraval, Valérie,Chauvin, Remi,Génisson, Yves
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- Low-valent dialkoxytitanium(ii): a useful tool for the synthesis of functionalized seven-membered ring compounds
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Herein, we describe unprecedented access to all-carbon or heterocyclic seven-membered ring frameworks from 1,8-ene-ynes promoted by inexpensive low-valent titanium(ii) species, readily available from Ti(OiPr)4and Grignard reagent. A broad range of cycloheptane, azepane or oxepane derivatives has been obtained (19 examples) with moderate to good yields and an excellent selectivity (up to 95/5 d.r.).
- Bodinier, Florent,Sanogo, Youssouf,Ardisson, Janick,Lannou, Marie-Isabelle,Sorin, Geoffroy
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supporting information
p. 3603 - 3606
(2021/04/14)
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- Development of a Radical Silylzincation of (Het)Aryl-Substituted Alkynes and Computational Insights into the Origin of the trans-Stereoselectivity
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Aryl- and hetaryl-substituted acetylenes undergo regio- and stereoselective silylzincation by reaction with [(Me3Si)3Si]2Zn in the presence of Et2Zn (10–110 mol%) as additive. The distinctive feature of this addition across the C?C triple bond is its trans stereoselectivity. The radical nature of the silylzincation process is supported by diagnostic experiments and DFT calculations, which also corroborate the role played by steric effects to obtain that stereoselectivity. The procedure can be combined in one-pot with the copper(I)-mediated electrophilic substitution of the C(sp2)?Zn bond, with retention of the double bond geometry. This makes it valuable for the synthesis of stereodefined di- and trisubstituted vinylsilanes. (Figure presented.).
- Romain, Elise,de la Vega-Hernández, Karen,Guégan, Frédéric,Sanz García, Juan,Fopp, Carolin,Chemla, Fabrice,Ferreira, Franck,Gerard, Hélène,Jackowski, Olivier,Halbert, Stéphanie,Oestreich, Martin,Perez-Luna, Alejandro
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supporting information
p. 2634 - 2647
(2021/03/30)
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- Ni-catalyzed direct carboxylation of propargylic alcohols with carbon dioxide
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The carboxylation of propargylic alcohols containing a silyl group at the terminal position was conducted in a CO2 atmosphere at atmospheric pressure in the presence of a nickel catalyst and diethylzinc. Here, CO2 was used as not only the C1 source but also the promoter of the COH cleavage processes for the oxidative addition of propargylic alcohols.
- Yamahira, Tatsuya,Onodera, Gen,Fukuda, Tsutomu,Kimura, Masanari
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supporting information
p. 853 - 855
(2021/05/19)
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- Copper-Catalyzed Modular Access to N-Fused Polycyclic Indoles and 5-Aroyl-pyrrol-2-ones via Intramolecular N—H/C—H Annulation with Alkynes: Scope and Mechanism Probes
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Copper-catalyzed intramolecular N—H/C—H annulation with alkynes has been developed. A variety of densely functionalized heterocycles, such as pyrrolo[1,2-a]indoles, indolo[1,2-c]quinazolin-2-ones, oxazolo[3,4-a]indoles, and imidazo[1,5-a]indoles, were synthesized in an atom- and step-economical manner, owing to the high modularized feature of aniline moiety, the linker moiety, as well as the alkyne moiety. By simply changing the oxidant from di-tert-butyl peroxide (DTBP) to 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), the reaction could readily be transformed to the aminooxygenation pathway, which grabs one oxygen atom from the TEMPO to generate 5-aroyl-pyrrol-2-ones. Mechanistic experiments indicate that vinyl radical is involved in this reaction and an amidyl-radical-initiated radical cascade might be responsible for this transformation.
- Liu, Yan-Hua,Song, Hong,Zhang, Chi,Liu, Yue-Jin,Shi, Bing-Feng
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supporting information
p. 1545 - 1552
(2020/09/09)
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- Catalytic Asymmetric Total Synthesis of Exiguolide
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The catalytic asymmetric total synthesis of (?)-exiguolide, a complex 20-membered macrolide embedded with a bis(tetrahydropyran) motif, is reported. The convergent synthesis involves the construction of the C1–C11 tetrahydropyran segment via catalytic asymmetric allylation and Prins cyclization, and the formation of the C12–C21 phosphonate segment via catalytic asymmetric cyclocondensation reaction and Johnson–Claisen rearrangement. The synthesis of 15-epi-exiguolide is also described.
- Oka, Kengo,Fuchi, Shunsuke,Komine, Keita,Fukuda, Hayato,Hatakeyama, Susumi,Ishihara, Jun
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supporting information
p. 12862 - 12867
(2020/09/16)
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- Exploring the scope of tandem palladium and isothiourea relay catalysis for the synthesis of α-amino acid derivatives
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The scope and limitations of a tandem N-allylation/[2,3]-rearrangement protocol are investigated through the incorporation of a variety of functional groups within an allylic phosphate precursor. This method uses readily accessible N,N-dimethylglycine aryl esters and functionalized allylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequent enantioselective [2,3]-sigmatropic rearrangement, promoted by the chiral isothiourea tetramisole, generates α-amino acid derivatives with two contiguous stereocenters. The incorporation of electron-withdrawing ester and amide groups gave the best results, furnishing the desired products in moderate to good yields (29-70percent), with low diastereocontrol (typically 60:40 dr) but high enantioselectivity (up to 90:10 er). These results indicate that substrate-catalyst interactions in the proposed transition state are sensitive to the substitution pattern of the substrates.
- Bitai, Jacqueline,Slawin, Alexandra M.Z.,Cordes, David B.,Smith, Andrew D.
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supporting information
(2020/07/27)
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- Iron-Catalyzed [2+2+2] Annulation of Aliphatic Bridged 1,n-Enynes with Aldehydes for the Synthesis of Fused Pyrans
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An iron-catalyzed [2+2+2] annulation of aliphatic bridged 1,n-enynes with aldehydes was developed. Aldehydes play a dual role as the precursors of acyl radicals to trigger the cascade cyclization but also as the radical acceptors to terminate the annulation. This two-in-one strategy overcomes the limitation in [2+2+m] cyclization that requires a rigid benzene skeleton as the essential linker, thus enabling the efficient synthesis of functionalized fused [5.6] and [6.6] pyran skeletons.
- Tian, Tian,Wang, Xin,Lv, Leiyang,Li, Zhiping
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supporting information
p. 4425 - 4428
(2020/06/05)
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- Catalyst-Free Annulation of 2-Pyridylacetates and Ynals with Molecular Oxygen: An Access to 3-Acylated Indolizines
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A catalyst and additive-free annulation of 2-pyridylacetates and ynals under molecular oxygen was the first developed, affording 3-acylated indolizines in good to excellent yields. Molecular oxygen was used as the source of the carbonyl oxygen atom in indolizines. This approach was compatible with a wide range of functional groups, and especially it has been successfully extended to unsaturated double bonds and triple bonds, which were difficult to prepare by previous methods in a single step.
- Chen, Zhengwang,Liang, Pei,Ma, Xiaoyue,Luo, Haiqing,Xu, Guohai,Liu, Tanggao,Wen, Xiaowei,Zheng, Jing,Ye, Hui
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supporting information
p. 1630 - 1639
(2019/01/26)
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- Direct Access to Allenylphosphine Oxides via a Metal Free Coupling of Propargylic Substrates with P(O)H Compounds
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A direct and convenient approach for the coupling of propargylic substrates with diphenylphosphine oxide in the presence of Tf2O and 2,6-lutidine has been developed. The method provides a general approach for the construction of attractive allenylphosphoryl skeletons with high atom and step economy under metal free conditions.
- Yang, Chun-Hua,Fan, Huihui,Li, Huimin,Hou, Shenyin,Sun, Xiangkun,Luo, Donghao,Zhang, Yinchao,Yang, Zhantao,Chang, Junbiao
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supporting information
p. 9438 - 9441
(2019/11/20)
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- Nickel-Catalyzed Direct Coupling of Allylic Alcohols with Organoboron Reagents
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The direct coupling of allylic alcohols with arylboronic acids or their derivatives catalyzed by Ni(cod)2 in the presence of a catalytic amount of base has been developed. A wide variety of allylic substrates or arylboronic acids turned out to be applicable to this catalytic system. The present method does not require the use of ligands for stabilizing the nickel catalyst in most cases or additional activators for activation of allylic alcohols.
- Wang, Gaonan,Gan, Yi,Liu, Yuanhong
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supporting information
p. 916 - 920
(2018/09/22)
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- Si-directed regiocontrol in asymmetric Pd-catalyzed allylic alkylations using C1-ammonium enolate nucleophiles
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Cooperative catalysis enables the direct enantioselective α-allylation of linear prochiral esters using Si-substituted allyl electrophiles. The Si-substituent directs the regioselectivity of enantioselective bond formation and provides products containing synthetically versatile pentafluorophenyl ester and vinylsilane moieties. Critical to the efficacy of this process was the recognition that the ancillary ligand on palladium could be altered to prevent formation of a deleterious ether by-product, whilst retaining enantioselectivity through the Lewis base catalyst. Flexibility such as this is unique to cooperative catalysis events and provides efficient access to an array of enantioenriched products that are orthogonally functionalized and easily modified.
- Fyfe, James W.B.,Kabia, Omaru M.,Pearson, Colin M.,Snaddon, Thomas N.
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supporting information
p. 5383 - 5391
(2018/04/23)
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- The influence of the organolithium reagent nature on the possibility of the O→Csp migration of the R3Si group in propynes HC≡CCH2OSiR3
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A possibility of the O→Csp 1,4-migration of the R3Si group in silyl ethers of terminal acetylenic alcohols upon treatment with organolithium reagents (RLi) was studied. In the case of 3-trimethylsilyloxypropyne, depending on the nature of RLi, the heterolysis of the Si—O bond occurs either by the action of acetylide formed as a result of deprotonation with the formation of 3-trimethylsilylprop-2-yn-1-ol trimethylsilyl ether, or by the action of the metalation agent with the formation of propargyl alcohol. The realization of the O→Csp 1,4-migration of the Me3Si group requires the use of mild organolithium reagents (lithium hexamethyldisilazanide and diisopropylamide). Silyl ethers having steric hindrance at the carbon atom bonded to the reaction center or around the silicon atom do not react with the studied organolithium reagents.
- Novokshonov,Medvedeva,Mareev
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p. 2264 - 2268
(2018/03/25)
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- Enantioselective Total Synthesis of Mandelalide A and Isomandelalide A: Discovery of a Cytotoxic Ring-Expanded Isomer
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The total synthesis of mandelalide A and its ring-expanded macrolide isomer isomandelalide A has been achieved. Unexpected high levels of cytotoxicity were observed with the ring-expanded isomandelalide A with a rank order of potency: mandelalide A > isomandelalide A > mandelalide B. Key aspects of the synthesis include Ag-catalyzed cyclizations (AgCC's) to construct both the THF and THP rings present in the macrocycle, diastereoselective Sharpless dihydroylation of a cis-enyne, and lithium acetylide coupling with a chiral epoxide.
- Veerasamy, Nagarathanam,Ghosh, Ankan,Li, Jinming,Watanabe, Kazuhiro,Serrill, Jeffrey D.,Ishmael, Jane E.,McPhail, Kerry L.,Carter, Rich G.
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supporting information
p. 770 - 773
(2016/02/05)
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- Synthesis and antiproliferative activity of new tonantzitlolone-derived diterpene derivatives
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The synthesis of the diterpene (+)-tonantzitlolone A and a series of derivatives is reported. The study includes the determination of their antiproliferative activities against selected cancer cell lines.
- Busch, Torsten,Dr?ger, Gerald,Kunst, Eike,Benson, Hannah,Sasse, Florenz,Siems, Karsten,Kirschning, Andreas
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supporting information
p. 9040 - 9045
(2016/10/07)
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- Enantioselective Carbene Cascade: An Effective Approach to Cyclopentadienes and Applications in Diels–Alder Reactions
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An asymmetric carbene cascade reaction, which proceeds through carbene/alkyne metathesis and formal (3+2) cycloaddition and converts alkynyl-tethered enol diazoacetates to chiral bicyclic cyclopentadienes, is presented; and no catalytic asymmetric version of these carbene cascade transformations has been disclosed so far. The proton signals of the cyclopropene intermediates are observed in the mechanism study, which clearly demonstrate the reaction pathways. In addition, these products are intercepted via Diels–Alder reactions to provide bridged polycyclic structures in high yields and enantioselectivities. (Figure presented.).
- Wang, Xiangbo,Zhou, Yunfei,Qiu, Lihua,Yao, Ruwei,Zheng, Yang,Zhang, Cheng,Bao, Xiaoguang,Xu, Xinfang
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supporting information
p. 1571 - 1576
(2016/10/13)
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- A new protocol for nickel-catalysed regio- and stereoselective hydrocyanation of allenes
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Regio- and stereoselective hydrocyanation under nickel catalysis is described. This report shows that allenyl C-C double bonds are discriminated and converted to the corresponding carbonitriles as a single product. The key functionalities for achieving high regio- and stereocontrol are aryl and cyclopropyl groups in the substrates. This journal is
- Arai, Shigeru,Hori, Hiroto,Amako, Yuka,Nishida, Atsushi
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supporting information
p. 7493 - 7496
(2015/05/04)
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- Synthesis and Isolation of Organogold Complexes through a Controlled 1,2-Silyl Migration
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During our efforts toward the synthesis of naturally occurring polyprenylated polycyclic acylphloroglucinol using a AuI-catalyzed 6-endo dig carbocyclization, we isolated stable vinyllic gold intermediates. Optimization lead to isolated yields of up to 98 %, using 2-(di-tert-butylphosphino)biphenyl as the ligand. This transformation is derived from a silyl rearrangement that can be fully controlled according to the nature of the substituent on the ynone. This selective transformation does not require basic conditions to prevent protodeauration. These vinylgold complexes are the first isolated intermediates during a silyl migration with gold(I). More than 16 new organogold complexes were synthesized and characterized by single-crystal X-ray diffraction. Reactivity of these complexes is also presented.
- McGee, Philippe,Bellavance, Gabriel,Korobkov, Ilia,Tarasewicz, Anika,Barriault, Louis
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supporting information
p. 9662 - 9665
(2015/06/30)
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- Evolution of an oxidative dearomatization enabled total synthesis of vinigrol
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The evolution of the synthetic strategy resulting in a total synthesis of vinigrol is presented. Oxidative dearomatization/intramolecular Diels-Alder cycloaddition has served as the successful cornerstone for all of the approaches. Extensive radical cyclization efforts to form the tetracyclic core resulted in interesting and surprising reaction outcomes, none of which could be advanced to vinigrol. These cyclization obstacles were successfully overcome by using Heck instead of radical cyclizations. The total synthesis features a trifluoroethyl ether protecting group being used for the first time in organic synthesis. The logic of its selection and the group's importance beyond protecting the C8a hydroxyl group is presented along with a discussion of strategies for its removal. Because of the compact tetracyclic cage the route is built around many unusual reaction observations and solutions have emerged. For example, a first of its kind Grob fragmentation reaction featuring a trifluoroethyl leaving group has been uncovered, interesting interrupted selenium dioxide allylic oxidations have been observed as well as intriguing catalyst and counterion dependent directed hydrogenations.
- Yang, Qingliang,Draghici, Cristian,Njardarson, Jon T.,Li, Fang,Smith, Brandon R.,Das, Pradipta
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supporting information
p. 330 - 344
(2014/01/06)
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- A cyclization-rearrangement cascade for the synthesis of structurally complex chiral gold(I)-aminocarbene complexes
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A facile synthesis of chiral cyclic alkyl aminocarbene-gold(I) complexes from gold-free 1,7-enyne substrates was developed. The novel cyclization-rearrangement reaction sequence is triggered by the addition of (Me2S)AuCl to different 1,7-enynes and leads to structurally unique carbene-gold(I) complexes in high yields. These novel complexes are catalytically active and inhibit the proliferation of different human cancer cell lines.
- Kolundzic, Filip,Murali, Annamalai,Perez-Galan, Patricia,Bauer, Jonathan O.,Strohmann, Carsten,Kumar, Kamal,Waldmann, Herbert
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supporting information
p. 8122 - 8126
(2014/08/18)
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- Design and synthesis of potent macrocyclic HIV-1 protease inhibitors involving P1-P2 ligands
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A series of potent macrocyclic HIV-1 protease inhibitors have been designed and synthesized. The compounds incorporated 16- to 19-membered macrocyclic rings between a nelfinavir-like P2 ligand and a tyrosine side chain containing a hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent than their corresponding acyclic counterparts. Saturated derivatives showed slight reduction of potency compared to the respective unsaturated derivatives. Compound 8a containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity. This journal is the Partner Organisations 2014.
- Ghosh, Arun K.,Schiltz, Gary E.,Rusere, Linah N.,Osswald, Heather L.,Walters, D. Eric,Amano, Masayuki,Mitsuya, Hiroaki
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p. 6842 - 6854
(2014/10/15)
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- Total synthesis of vinigrol
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Carbocyclic cage fight: The substrate-controlled total synthesis of vinigrol features a strategic oxidative dearomatization/Diels-Alder cycloaddition reaction and a subsequent palladium-catalyzed cyclization cascade to construct the carbocyclic core. The C4, C9, and C12 stereocenters were installed using either reduction or oxidation reactions, and the diterpenoid core was unraveled by a ring fragmentation reaction. Copyright
- Yang, Qingliang,Njardarson, Jon T.,Draghici, Cristian,Li, Fang
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supporting information
p. 8648 - 8651
(2013/09/12)
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- Stereocontrolled synthesis of a Cn-Cn+7 building block ("eastern moiety") for the unnatural enantiomers of important polyol,polyene antibiotics based on a ring-closing metathesis and an aldol addition of a lactone enolate
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A stereocontrolled synthesis of epoxide 6, which represents the C n-Cn+7 or "eastern moiety" building block for the title compounds, has been realized in 19 steps. Our synthesis started from tetrabromoacetone 26 and afforded dibromotriene 33b in six steps. The latter was subjected to a ring-closing metathesis, which gave the dibromovinyl-substituted lactone 34 in high yield. A highly stereoselective conjugate addition/enolate aldolization sequence established the additional stereocenters with perfect selectivity. Epoxide 47b was reached in another eight steps, which included a C-SiMe2Pha€‰→a€‰C-OH oxidation in the presence of an acetal group. The final structure 6 was completed by hydrostannylation/brominolysis. A dibromovinyl-substituted unsaturated δ-lactone obtained by ring-closing metathesis underwent a highly diastereoselective silyl cuprate 1,4-addition/aldolization sequence. Tamao-Fleming oxidation transformed the silyl into a hydroxy group. Alkyne formation, hydrostannylation, and N-bromosuccinimidolysis converted the dibromovinyl into a trans-bromovinyl moiety. Copyright
- Kamptmann, Sonja B.,Brueckner, Reinhard
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supporting information
p. 6584 - 6600
(2013/11/06)
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- Bifunctional iron complexes: Efficient catalysts for C=O and C=N reduction in water
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The application of bifunctional iron complexes for the hydrogenation of polarized C=X bonds is reported. Two modified Knoelker complexes bearing ionic fragments were synthesized and fully characterized. With these well-defined complexes, the reaction proceeded under mild conditions in pure water, and various alcohols and amines were isolated in good yields. Compared with hydrogenation in organic solvents, better reactivities were observed. Is this the iron age? Well-defined iron-complex-catalyzed reduction of aldehydes, ketones, and imines using molecular hydrogen in water is presented. Under mild conditions, good yields for a broad range of substrates are achieved.
- Merel, Delphine S.,Elie, Margaux,Lohier, Jean-Francois,Gaillard, Sylvain,Renaud, Jean-Luc
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p. 2939 - 2945
(2013/10/21)
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- Studies towards the identification of the sex pheromone of Thyrinteina arnobia
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The eucalyptus brown-looper Thyrinteina arnobia (Lepidoptera: Geometridae) is considered an important pest in Brazilian native plants, e.g. Psidium guajava, and exotic plants, such as Eucalyptus species. In this work we describe the isolation of the pheromone components of T. arnobia, using glands extract and solid phase micro extraction (SPME) of virgin females. The samples were analyzed by gas chromatography with an electroantennographic detector (GC-EAD), and mass spectrometry (GC-MS). Two reproducible electroantennographic responses were elicited in the male antenna of T. arnobia and one of them was identified as 3,4-epoxy-6,9-heneicosadiene by CG-MS. The racemic synthesis of this epoxydiene was carried out in 10 steps and 28percent overall yield. The four stereoisomers of the epoxydiene were also synthesized employing the corresponding enantiomeric enriched epoxyalcohols.
- Moreira, Jardel A.,Neppe, Tiago,De Paiva, Marcelo M.,Deobald, Anna M.,Batista-Pereira, Luciane G.,Paixa?o, Marcio W.,Corre?a, Arlene G.
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p. 1933 - 1941
(2014/01/06)
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- Carboxylate-directed tandem functionalisations of α,β- dihaloalkenoic acids with 1-alkynes: A straightforward access to (Z)-configured, α,β-substituted γ-alkylidenebutenolides
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An easy and mild copper(I)-catalysed lactonisation of readily available (E)-2,3-dihalopropenoic acid derivatives regio- and stereoselectively leads to rarely described (Z)-3-halo-5-ylidene-5H-furan-2-ones. These compounds are subsequently able to undergo classical Pd-catalysed cross-coupling reactions, providing 3-substituted and 3,4-disubstituted 5-ylidene-5H-furan-2-ones (see scheme).
- Inack Ngi, Samuel,Cherry, Khalil,Héran, Virginie,Commeiras, Laurent,Parrain, Jean-Luc,Duchêne, Alain,Abarbri, Mohamed,Thibonnet, Jér?me
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supporting information; experimental part
p. 13692 - 13696
(2012/01/06)
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- Highly stereoselective total synthesis of fully hydroxy-protected mycolactones A and B and their stereoisomerization upon deprotection
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Unprecedentedly efficient and highly (≥98 %) stereoselective syntheses of mycolactones A and B side chains relied heavily on Pd-catalyzed alkenylation (Negishi version) and were completed in 11 longest linear steps from ethyl (S)-3-hydroxybutyrate in 12 % and 11 % overall yield, respectively, roughly corresponding to an average of 82 % yield per step. The synthesis of mycolactone core was realized by using Pd-catalyzed alkenyl-allyl coupling and an epoxide-opening reaction with a trialkylalkenylaluminate as key steps. Fully hydroxy-protected mycolactones A and B of ≥98 % isomeric purity were synthesized successfully for the first time. However, unexpected 4:3-5:4 inseparable mixtures of mycolactones A and B were obtained upon deprotection. Copyright
- Wang, Guangwei,Yin, Ning,Negishi, Ei-Ichi
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scheme or table
p. 4118 - 4130
(2011/05/17)
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- Radical zinc-atom transfer based multicomponent approaches to 3-alkylidene-substituted tetrahydrofurans
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A domino 1,4-addition/alkyne carbozincation sequence based on a radical zinc-atom transfer process is disclosed. Two efficient multicomponent approaches to 3-alkylidenetetrahydrofurans from -(propargyloxy)enoates bearing pendant alkynes (including ynamides) have been established: one involving the direct addition of dialkylzincs, and the second involving the dimethylzinc-mediated addition of alkyl iodides. Both sequences utilize the stereoselective formation of intermediate alkylidenezincs well suited for in situ functionalization with electrophiles. 1 Introduction 2 1,4-Addition/Cyclization of Dialkylzincs on -(Propargyloxy)enoates 2.1 -(Propargyloxy)enoates with a Pendant Terminal Alkyne 2.2 -(Propargyloxy)enoates with a Pendant Substituted Alkyne 2.3 -(Propargyloxy)enoates with a Pendant Ynamide 3 1,4-Addition/Cyclization of Alkylzinc Halides on -(Propargyloxy)enoates 4 Dialkylzinc-Mediated 1,4-Addition/Cyclization of Alkyl Iodides on -(Propargyloxy)enoates 5 Conclusion; Current and Future Work. Georg Thieme Verlag Stuttgart New York.
- Chemla, Fabrice,Dulong, Florian,Ferreira, Franck,Nuellen, Max P.,Perez-Luna, Alejandro
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scheme or table
p. 1347 - 1360
(2011/06/10)
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- Highly branched and hyperbranched glycopolymers via reversible addition-fragmentation chain transfer polymerization and click chemistry
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We report a new strategy to synthesize densely functionalized highly and hyperbranched glycopolymers. Our methodology combines living radical polymerization and click chemistry. Hyperbranched "clickable" scaffolds synthesized via RAFT polymerization are functionalized with carbohydrate groups using an array of "click" chemistry reactions, namely Cu(I)-catalyzed Huisgen 1,3-cycloaddition of azides and alkynes (CuAAC), thiol-ene addition, and thiol-yne addition. This simple and flexible method yields glycopolymers of unique structures, which are potential candidates for biomedical applications.
- Semsarilar, Mona,Ladmiral, Vincent,Perrier, Sebastien
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experimental part
p. 1438 - 1443
(2011/09/20)
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- Efficient synthesis of nevirapine analogs to study its metabolic profile by click fishing
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Knowledge of the biotransformation and pharmacokinetics of the antiretroviral agent nevirapine is still insufficient. In order to trace rash inducing metabolites of nevirapine, we devised a short and efficient multi-gram synthesis of a nevirapine analog that can be coupled to azide containing compounds by click chemistry.
- Bernard, Sylvain,Defoy, Daniel,Dory, Yves L.,Klarskov, Klaus
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supporting information; experimental part
p. 6127 - 6130
(2010/06/13)
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- "Clicking" polymer brushes with thiol-yne chemistry: Indoors and out
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(Chemical Equation Presented) Thiol-yne click chemistry is demonstrated as a modular platform for rapid and practical fabrication of highly functional, multicomponent surfaces under ambient conditions. The principle is illustrated using a postmodification strategy in which poly(propargyl methacrylate) brushes were generated via surface-initiated photopolymerization and sequentially functionalized using the radical-mediated thiol-yne reaction. Brush surfaces expressing a three-dimensional configuration of "yne" functionalities were modified with high efficiency and short reaction times using a library of commercially available thiols, including functional thiols that demonstrate applicability for pH responsive surfaces and for bioconjugation. Sequential thiol-yne reactions in conjunction with simple UV photolithography were also applied to afford micropatterned, multicomponent surfaces. The practicality of the platform was further demonstrated by carrying out thiol-yne surface reactions in sunlight, suggesting the possibility of large scale modifications using renewable energy resources. Considering the mild reaction conditions, rapid throughput, and compatibility with orthogonal chemistries, we expect this platform to find widespread use among the materials science community.
- Hensarling, Ryan M.,Doughty, Vanessa A.,Chan, Justin W.,Patton, Derek L.
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supporting information; experimental part
p. 14673 - 14675
(2010/01/06)
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- Asymmetric synthesis of α-allenylglycines
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The coupling of the homocuprate of the bislactim ether of cyclo-(-L-Val-Gly-) (9) with primary propargyl halides produces the allenyl-substituted bislactim ethers 11 in a highly diastereoselective manner, whereas the alkylation of the lith-iated bislactim ether of cyclo-(-L-Val-Gly-) yields the proparg-yl-substituted bislactim ethers 12. Subsequent hydrolysis affords, after protection of the amino group, the methyl α- allenylglycinates 15, the α-allenylglycines 16, and the methyl α-propargylglycinates 17.
- Bucuroaia, Carmen,Groth, Ulrich,Huhn, Thomas,Klinge, Michael
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experimental part
p. 3605 - 3612
(2009/12/01)
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- Improved method for the synthesis of β-carbonyl silyl-1,3-dithianes by the double conjugate addition of 1,3-dithiol to propargylic carbonyl compounds
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(Chemical Equation Presented) Base-mediated double conjugate addition of 1,3-propane dithiol to various silylated propargylic aldehydes and ketones allows for an efficient and scalable synthesis of β-carbonyl silyl-1,3-dithianes.
- Mukherjee, Sumit,Kontokosta, Dimitra,Patil, Aditi,Rallapalli, Sivakumar,Lee, Daesung
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supporting information; experimental part
p. 9206 - 9209
(2010/03/02)
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- In situ "click" assembly of small molecule matrix metalloprotease inhibitors containing zinc-chelating groups
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(Chemical Equation Presented) A panel of small molecule-based MMP inhibitors containing rhodanine warheads was assembled using "one-pot" click chemistry. Upon biological screening, moderate inhibitors were identified which specifically targets MMP-7 and MMP-13 over other MMPs.
- Hu, Mingyu,Li, Junqi,Yao, Shao Q.
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supporting information; experimental part
p. 5529 - 5531
(2009/06/17)
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- Enantioselective synthesis of allylsilanes bearing tertiary and quaternary si-substituted carbons through Cu-catalyzed allylic alkylations with alkylzinc and arylzinc reagents
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All sorts of allylsilanes including, for the first time, those that contain a Si-bonded quaternary carbon, were synthesized through efficient and highly enantioselective Cu-catalyzed asymmetric allylic alkylations. Reactions may involve dialkyl- as well as diarylzinc reagents and are promoted by various chiral N-heterocyclic carbene complexes.
- Kacprzynski, Monica A.,May, Tricia L.,Kazane, Stephanie A.,Hoveyda, Amir H.
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p. 4554 - 4558
(2008/09/17)
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- Fluorination process
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Compounds of formula (II), (IIIa) or (IIIb) (variables are described in the specification) are prepared by fluorination of β,γ-unsaturated alkyl silanes. These compounds are useful as building blocks in the pharmaceutical industry.
- -
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Page/Page column 26
(2008/06/13)
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- trans-hydroalumination/alkylation: One-pot synthesis of trisubstituted allylic alcohols
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Described herein is a method of stereoselective synthesis of trisubstituted allylic alcohols by alkylation of alkenyl alanates, formed in situ through treatment of propargyl alcohols with Vitride (Red-Al). This technique represents the first of its kind to feature a trans-hydrometalation, and is particularly effective for the formation of 1,4-dienes. Applications involving primary, secondary, and tertiary alcohols are discussed, as well as limitations regarding both alkyne and electrophile components.
- Langille, Neil F.,Jamison, Timothy F.
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p. 3761 - 3764
(2007/10/03)
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- Formal enantioselective synthesis of (+)-compactin
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The challenging structural features and important biological activity of (+)-compactin (1) explain the substantial synthetic interest that it has generated. We report a novel enantioselective approach to the advanced intermediate 2a, which constitutes a formal synthesis of (+)-1. The sequence utilizes MacMillan's organocatalytic Mukaiyama-Michael reaction, which stereoselectively adds the silyloxyfuran 6 to α,β-unsaturated aldehyde 7. The chirality generated in this reaction guides the formation of the other three consecutive stereocenters found in 2a.
- Robichaud, Joel,Tremblay, Francois
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p. 597 - 600
(2007/10/03)
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- Synthesis of propargylic fluorides from allenylsilanes
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Allenylsilanes reacted at room temperature in acetonitrile with Selectfluor, an electrophilic fluorinating reagent, to give secondary propargylic fluorides in moderate to good yields; mechanistically, a side-product resulting from a 1,2-silyl shift testifies to the presence of a cationic intermediate. The Royal Society of Chemistry 2006.
- Carroll, Laurence,Pacheco, Ma. Carmen,Garcia, Ludivine,Gouverneur, Veronique
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p. 4113 - 4115
(2007/10/03)
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- Stereoselective syntheses of dihydroxerulin and xerulinic acid, anti-hypocholesterolemic dyes from the fungus Xerula melanotricha
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The title compounds 2 and 3, which are inhibitors of the biosynthesis of cholesterol, were synthesized in a convergent and perfectly stereoselective manner. In the key step, bromobutenolide 6 (obtained from levulinic acid in two steps) was coupled with either of the novel bis(stannanes) trans,cis, -trans-35 or trans,trans,trans-35 [each accessible from 3-(tributylstannyl)allyl alcohol (17) in four steps], giving γ-alkylidenebutenolide trans,trans,trans-32. This compound was coupled with iododiyne 42 or the bromoenediynoate 44 leading to dihydroxerulin (2) and to the (trimethylsilylethyl)ester 45 of xerulinic acid, respectively. Deprotection of the latter provided totally synthetic xerulinic acid (3) for the first time.
- Sorg, Achim,Siegel, Konrad,Brueckner, Reinhard
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p. 1610 - 1624
(2007/10/03)
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- Syntheses of seven-membered rings: Ruthenium-catalyzed intramolecular [5+2] cycloadditions
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The Ru-catalyzed intramolecular [5+2] cycloaddition of cyclopropylenynes is investigated with respect to the regio- and diastereoselectivity as well as the functional group compatibility of the reaction. Evidence for the mechanism as occurring through a ruthenacyclopentene intermediate is elucidated from 1) the study of the diastereoselectivity of the cycloaddition; 2) the effect of variation of substituents on the regioselectivity of cyclopropyl bond cleavage in 1,2-trans- and 1,2-cis-disubstituted cyclopropanes and 3) examples that clearly do not involve ruthenacyclohexene as intermediates as products still incorporate the cyclo propyl moiety. The scope and limitations of the Ru-catalyzed cycloaddition are discussed and compared with the Rh-catalyzed reaction. The potential power of this methodology towards natural product total synthesis is demonstrated by the formation of several polycyclic systems with the chosen reaction conditions and readily available cyclopropylenyne substrates.
- Trost, Barry M.,Shen, Hong C.,Horne, Daniel B.,Toste, F. Dean,Steinmetz, Bernhard G.,Koradin, Christopher
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p. 2577 - 2590
(2007/10/03)
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- Transition-metal-mediated synthesis of novel carbocyclic nucleoside analogues with antitumoral activity
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A diversity-oriented, enantioselective synthesis of new (monoprotected) carbocyclic nucleoside analogues (CNAs) with the nucleobase attached to a 3-hydroxymethyl-4-trialkylsilyloxymethylcyclopent-2-en-l -yl scaffold was developed. As a key intermediate, racemic (5SR,8RS)-8-allyloxy-2-trimethylsilyl- 7-oxa-bicyclo[3.3.0]-oct-1-en-3-one was prepared from 1,1-diallyloxy-3- trimethylsilyl-2-propyne in a cobalt-mediated Pauson-Khand reaction. The enantiomerically pure material was obtained through efficient kinetic resolution (selectivity factor s ≥ 40 at -78°C) by means of an oxazaborolidine- catalyzed borane reduction (CBS reduction) with catecholborane. The absolute configuration of the resolved products was determined by CD spectroscopy, Mosher ester analysis, and chemical correlation. Subsequent steps involve diastereoselective ketone reduction and fully regio- and diastereoselective introduction of the nucleobase through Pd°-catalyzed allylic substitution. The generality of the method was demonstrated by preparation of CNAs in both enantiomeric series with all five natural nucleobases, as well as 5-bromouracil, 5-fluorouracil, and 6-chloropurine. Screening of the various compounds in a cytotoxicity assay with BJAB and ALL tumor cell lines revealed that some of the compounds possess pronounced antitumoral properties (LD50 values down to 9 μM, as determined by lactate dehydrogenase release after 48 h). By measuring DNA fragmentation, it could be shown that the activity results from induction of apoptosis.
- Velcicky, Juraj,Lanver, Andreas,Lex, Johann,Prokop, Aram,Wieder, Thomas,Schmalz, Hans-Guenther
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p. 5087 - 5110
(2007/10/03)
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- Titanium(IV) bromide promoted diastereoselective reactions of arylaldehydes with optically active propiolates
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The diastereoselective condensation reaction of arylaldehydes with optically active derivatives of propynoic acid has been examined in the presence of the Lewis acid titanium(IV) bromide (TiBr4); we have found that moderate to excellent diastereomeric excess (de) can be achieved in this TiBr4-promoted reaction.
- Shi, Min,Wang, Chun-Jiang
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p. 107 - 110
(2007/10/03)
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- Part 1: Efficient strategies for the construction of variably substituted bicyclo[5.3.1]undecenones (AB taxane ring systems)
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Strategies for the construction of cyclic molecules containing variably substituted bicyclo[5.3.1]undecenones (AB taxane ring systems) are described. These routes employ a multi-component coupling protocol that utilizes sequential magnesium-mediated carbometallation of propargyl alcohols and intramolecular Diels-Alder reactions (IMDA). The cycloaddition generates the key eight-membered taxane ring as a single diastereomer, induced by preferential Lewis acid (diethylaluminum chloride or boron trifluoride etherate) complexation with the cross-ring oxygens, Both the electronic nature of the dienophile and the neighbouring group non-bonded interactions contribute to the success of these cycloadditions.
- Laurent, Alain,Villalva-Servin, Nidia P.,Forgione, Pat,Wilson, Peter D.,Smil, David V.,Fallis, Alex G.
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p. 215 - 226
(2007/10/03)
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- Part 2: Efficient strategies for the construction of variably substituted bicyclo[5.3.1]undecenones (AB-taxane ring systems) and their conversion to tricyclo[9.3.1.03,8]pentadecenones (ABC taxane ring systems) and bicyclo[2.2.2]octanones
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The extension of our strategies for the construction of cyclic molecules containing variably substituted bicyclo[5.3.1]undecenones (AB taxane ring systems) for the synthesis of the tricyclo[9.3.1.03,8]pentadecenone (ABC taxane ring system) and bicyclo[2.2.2]octanones are described. These routes employ a multi-component coupling protocol that employs sequential magnesium-mediated carbometallation of allyl-substituted propargyl alcohols followed by diastereoselective Lewis acid catalyzed intramolecular Diels-Alder reactions (TMDA). Subsequent ring-closing metathesis (RCM) afforded the ABC taxane core structure. Enone accelerated [3,3] sigmatropic rearrangements (Cope rearrangements) generated the bicyclo[2.2.2]octanone nucleus. In the presence of a Lewis acid, the dienophile precursor underwent a tandem reaction via the adduct directly to the bicyclo[2.2.2]octanones. This is the first example of a novel enone accelerated carbocycle Cope rearrangement and provides direct access to bicyclo[2.2.2]octanones by a new route that compliments the traditional cyclohexadiene cycloaddition approach.
- Villalva-Servin, Nidia P.,Laurent, Alain,Fallis, Alex G.
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p. 227 - 239
(2007/10/03)
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- Total synthesis of (+)-crocacin A
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Total synthesis of the potent antifungal and cytotoxic agent (+)-crocacin A is described. The crucial (Z)-5,6-enoic amide moiety in this molecule was built by stereoselective partial reduction of a skipped diyne precursor. The diene, thus obtained, was transformed into a silyl epoxide that was regioselectively opened with an azide ion to furnish an α-azido-β-hydroxyalkylsilane intermediate. Peterson elimination of this β-hydroxysilane component in the final step resulted in the formation of the (Z)-8,9-enamide moiety of the molecule leading to a successful completion of its total synthesis.
- Chakraborty, Tushar K.,Laxman, Pasunoori
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p. 4989 - 4992
(2007/10/03)
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- An efficient organometallic approach to new carbocyclic nucleoside analogues.
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[reaction: see text] A general synthetic approach to monoprotected carbocyclic nucleoside analogues, having the nucleobase attached to a 3-hydroxymethyl-4-trialkylsilyloxymethyl-cyclopent-2-en-1-yl scaffold, was developed. A (racemic) key intermediate was prepared by a cobalt-mediated Pauson-Khand reaction. In the course of the further synthesis, the introduction of the nucleobase was achieved with complete regio- and diastereoselectivity through a palladium-catalyzed allylic substitution.
- Velcicky, Juraj,Lex, Johann,Schmalz, Hans-Guenther
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p. 565 - 568
(2007/10/03)
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- Allylsilane-modified amino acids from the Claisen rearrangement
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The Claisen rearrangement of the N-protected, silylated allyl glycinates 11 and 12 led to the formation of allyl/silyl-functionalized amino acids 13 and 14 in yields up to 80%. The diastereoisomer ratio varied from 2:1 to 29:1 for 11mb, and from 2:1 to 46:1 (syn/anti) for 12mb, depending on reaction conditions, as shown by X-ray crystallographic analysis of 14mb. The relationship between the size of the alkyl groups on the chlorosilane reagent (Me2R″SiCl, R″ = Cl, Me, t-Bu, Ph) used as an enolate trap and the observed stereoselectivity was investigated in the case of the Ireland - Claisen variant. Me3SiCl gave the best results. However, the size of the alkyl groups on the silylated ester (Me2R″Si, R = Me, t-Bu, Ph, i-Pr) did not exert a significant effect on the diastereoselectivity or yield of the rearrangement.
- Mohamed, Mustafa,Brook, Michael A.
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p. 4165 - 4181
(2007/10/03)
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- Synthetic studies toward bioactive cyclic peroxides from the marine sponge Plakortis angulospiculatus
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(formula presented) The total synthesis of two stereoisomers of a bioactive cyclic peroxide isolated from the marine sponge Plakortis angulospiculatus has been achieved in 18 steps with an overall yield of 2.8%. Diels-Alder addition of singlet oxygen to an acyclic triene carboxylic acid precursor was used to construct the 3,6-dihydro-1,2-dioxin ring. By comparing spectral data of the synthesized compounds and the natural material, we tentatively assign the absolute stereochemistry for the natural product as 3S,6R,8S,10R.
- Yao, Gang,Steliou, Kosta
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p. 485 - 488
(2007/10/03)
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