Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• metal complexes As the protein host, the FhuA ΔCVFtev variant of the Ferric hydroxamate uptake protein component A (FhuA) was chosen [31]. This protein was shown to be suitable to harbor Grubbs–Hoveyda type catalysts for olefin metathesis [17][18]. To anchor Cu(I) in the protein FhuA ΔCVFtev that

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• . Some of these post-MCR transformations are: intramolecular cycloaddition reactions, Knoevenagel condensations, metathesis reactions, aza-Wittig reactions, Mitsunobu reactions, etc. [21]. Up to now, two review articles have been reported on azaheterocyclic phosphonates [22][23], but no overview article

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• -metathesis of a challenging homoallylic urea substrate, which proceeds in good yields in the presence of an organic phosphoric acid. Keywords: cross-metathesis; natural products; pyrimidines; Tsuji–Trost reaction; synthetic methods; Introduction Chiral pyrimidine motifs constitute prevalent structural

• substrate 14 was prepared from amine 12 by cross-metathesis with 2-butene-1,4-diol (13) in the presence of Grubbs-II catalyst 21. However, in the subsequent coupling reactions of 14 with TsNCO it became apparent that this homoallylic amine was too unreactive to enable a double addition to access 15 directly

• . Therefore, a stepwise approach towards 19 was pursued instead. This involved either a coupling of 12 first with isocyanate to give 16 followed by a cross-metathesis or starting with the cross-metathesis to 18 and subsequent installment of the urea motif. As shown in the table inserted in Scheme 3 for

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• -selective hydrogenation of the internal alkyne would present an efficient method for the synthesis of the 13-membered ring. The synthesis of the 11-membered ring could be achieved by a Z-selective alkene RCM reaction [5] to afford spirocyclic bislactam 4 from metathesis precursor 5. Bisalkene 5 could in

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• larger groups via cross-metathesis. The method was applied in the synthesis of a new pantothenamide with improved stability in human blood. Keywords: antibiotic; antiplasmodial; coenzyme A; metathesis; pantothenate; Introduction Bacteria, fungi, and parasites are all rapidly acquiring resistance to

• at the geminal dimethyl group. This route takes advantage of the reported path to 2 combined with cross-metathesis. Results and Discussion Establishing the synthetic route Based on the success of the synthetic route published by Akinnusi et al. [18] to generate derivatives modified at the geminal

• dimethyl moiety of pantothenamides, it was envisaged that allyl derivatives, such as 2 or its precursors, could be good starting points to add larger moieties via cross-metathesis [19]. Two cross-metathesis catalysts were used here (Figure 2): Grubbs’ 2nd generation catalyst (3) and the more versatile

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• metathesis (RCM) [68]. The insertion of the rhodium carbenoids derived from vinyl diazoacetate into the C(sp3)–H bonds of the alkenylcarbamates 97a–d yields two reaction products (Table 10). The major one (99a–d) was the result of the cyclopropanation reaction of the double bond present in 97a–d. The minor

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

• Julia Wappel,
• Roland C. Fischer,
• Luigi Cavallo,
• Christian Slugovc and
• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 154–165, doi:10.3762/bjoc.12.17

• 10.3762/bjoc.12.17 Abstract A straightforward synthesis utilizing the ring-opening metathesis polymerization (ROMP) reaction is described for acid-triggered N,O-chelating ruthenium-based pre-catalysts bearing one or two 8-quinolinolate ligands. The innovative pre-catalysts were tested regarding their

• behavior in ROMP and especially for their use in the synthesis of poly(dicyclopentadiene) (pDCPD). Bearing either the common phosphine leaving ligand in the first and second Grubbs olefin metathesis catalysts, or the Ru–O bond cleavage for the next Hoveyda-type catalysts, this work is a step forward

• towards the control of polymer functionalization and living or switchable polymerizations. Keywords: acid; activation by acid; metathesis; polymer; quinolin; ruthenium; triggerable; Introduction The modulation of the activity of enzymes by chemical triggers, e.g., by allosteric binding is ubiquitous in

Versatile deprotonated NHC: C,N-bridged dinuclear iridium and rhodium complexes

• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 117–124, doi:10.3762/bjoc.12.13

• effective for any catalytic reaction, but some successful applications were achieved in the field of Ru-catalyzed metathesis of olefins [9][10][11][12], Ir-catalyzed hydrogenation [13][14], Pd-catalyzed C=C coupling reactions [15][16], Ir-catalyzed CO2 fixation [17][18], and/or functionalization of alkenes

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• ], multicomponent reactions [8], ring-closing metathesis approaches [9][10], tandem reactions of 1,3-dicarbonyl compounds [11][12] and cyclocondenzation reactions of salicylic aldehydes with α,β-unsaturated carbonyl compounds [13][14][15]. The utility of some of these methods are limited by drawbacks such as

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• catalysts were tested in toluene or ethyl acetate, and found to afford metathesis products in high yield and with extremely low ruthenium contamination. Depending on the support used, immobilised catalyst 8 shows also additional traits, such as the possibility of being magnetically separated or the use for

• metathesis and subsequent reduction of the obtained double bond in one pot. Keywords: catalysis; immobilisation; N-heterocyclic carbenes; olefin metathesis; ruthenium; Introduction Over the past decade olefin metathesis has undergone a grand development. The design of stable and active ruthenium-based

• metathesis catalysts has been the cardinal factor to distribute olefin metathesis in the synthesis of many important compounds [1][2][3][4]. Commercially available homogeneous complexes, including phosphine-containing Gru-II, Ind-II or phosphine-free Hov-II and Gre-II are usually employed in such cases

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• compounds even at 0 °C. It was also examined in more demanding systems such as conjugated dienes and polyenes. The catalyst is stable, storable and easy to purify. Keywords: chromane derivatives; metathesis catalyst; nitrogen heterocycles; olefin metathesis; Ru-carbene; Introduction Olefin metathesis is

• still one of the most intensively studied transformations in synthetic organic chemistry. It has been frequently used as a key bond-forming reaction for total syntheses of many natural products [1]. The study on designing new metathesis catalysts and their synthesis has been a very fast developing area

• of organic chemistry since 1992, when Grubbs discovered the first well-defined ruthenium catalyst [2]. Nearly 400 ruthenium heterocyclic carbene-coordinated olefin metathesis catalysts were prepared until 2010 [3]. Since 2011, when Grubbs reported the synthesis of a Z-selective catalyst [4], several

Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• as prepared by controlled living ring-opening metathesis polymerization (ROMP) of the respective metal-incorporating monomers. Ferrocene- and other metallocene-modified polymers, macromolecules including metal-carbonyl complexes, polymers tethering early or late transition metal complexes, etc. are

• herein discussed. Recent advances in the design and syntheses reported mainly during the last three years are highlighted, with special emphasis on new trends for superior applications of these hybrid materials. Keywords: advanced materials; metallopolymers; metathesis; ROMP; transition metals

• ) polymerization [15][16], living ionic polymerizations, specifically ring-opening polymerization (ROP) [17], as well as migration insertion polymerization (MIP) [18], acyclic diene metathesis polymerization (ADMET) [19][20] and ring-opening metathesis polymerization (ROMP) [21][22][23][24][25][26][27]. These

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• . Different strategies for the construction of E- or Z-cyclononenes have been reported to date and common reactions are summarized in Scheme 3. Transition metal-catalyzed ([M] = Ru, Mo, W) ring-closing metathesis (RCM) reactions of 1,10-dienes A can be employed for the synthesis of cyclononenes. The E/Z

• ring segment. The application of this useful intermediate was elegantly demonstrated in the synthesis of coraxeniolide A proceeding in 14% yield over five steps. Altmann and co-workers disclosed the total synthesis of blumiolide C (11) [20] employing a Z-selective ring-closing metathesis reaction for

• with acryloyl chloride gave ester 87 and a ring-closing metathesis reaction using Grubbs second generation catalyst [50] furnished an α,β-unsaturated lactone. Subsequent 1,4-addition of the cuprate derived from alkylmagnesium chloride 88 provided the trans-product with excellent diastereoselectivity

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

• Jyotiprasad Mukherjee,
• Suman Sil and
• Shital Kumar Chattopadhyay

Beilstein J. Org. Chem. 2015, 11, 2487–2492, doi:10.3762/bjoc.11.270

• which involves a late-stage functionalization of a macrocyclic scaffold through cross metathesis in an attempt to create diversity. The utility of this protocol is demonstrated through the preparation of three structural analogues of the important naturally occurring histone deacetylase inhibitor FR

• -225497. Keywords: cross metathesis; cyclic peptides; diversity oriented synthesis; macrocycle; Introduction Diversity-oriented synthesis (DOS) has been established as an important paradigm in drug discovery [1][2][3][4][5][6][7]. Although the major focus is on the synthesis of small molecular libraries

• differ in their end groups. Although there are excellent synthetic approaches to nearly all of such known targets [15], the development of a simple diversity-oriented approach suitable for modification of the compounds remains desirable. Results and Discussion We thought that a cross metathesis reaction

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• ring closing metathesis to afford the bicyclic product 53. Finally, the RCM of the 1,4-adduct resulting from the addition of 3-butenylmagnesium bromide yielded the spiro compound 54. Interestingly, the conversion of bicyclic compound 40 catalyzed by the same system also occurred selectively in the 4

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• just a single example, NHC ligands played a crucial role in the development of highly efficient ruthenium initiators for olefin metathesis and related reactions [18][19][20][21]. Lately, these divalent carbon species have also emerged as powerful nucleophilic organocatalysts for polymer chemistry [22

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• Alkenes containing N-heteroaromatics are known to be poor partners in cross-metathesis reactions, probably due to catalyst deactivation caused by the presence of a nitrogen atom. However, some examples of ring-closing and cross-metathesis involving alkenes that incorporate N-heteroaromatics can be found

• in the literature. In addition, recent mechanistic studies have focused on the rationalization of nitrogen-induced catalysts deactivation. The purpose of this mini-review is to give a brief overview of successful metathesis reactions involving olefins containing N-heteroaromatics in order to

• delineate some guidelines for the use of these challenging substrates in metathesis reactions. Keywords: catalyst deactivation; cross-metathesis; N-heteroaromatic; pyridine; ring-closing metathesis; Introduction Over the past decades, metathesis has become a key reaction within the organic chemist’s

Computational study of productive and non-productive cycles in fluoroalkene metathesis

• Markéta Rybáčková,
• Jan Hošek,
• Ondřej Šimůnek,
• Viola Kolaříková and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2015, 11, 2150–2157, doi:10.3762/bjoc.11.232

• Marketa Rybackova Jan Hosek Ondrej Simunek Viola Kolarikova Jaroslav Kvicala Department of Organic Chemistry, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic 10.3762/bjoc.11.232 Abstract A detailed DFT study of the mechanism of metathesis of fluoroethene, 1

• -fluoroethene, 1,1-difluoroethene, cis- and trans-1,2-difluoroethene, tetrafluoroethene and chlorotrifluoroethene catalysed with the Hoveyda–Grubbs 2nd generation catalyst was performed. It revealed that a successful metathesis of hydrofluoroethenes is hampered by a high preference for a non-productive

• catalytic cycle proceeding through a ruthenacyclobutane intermediate bearing fluorines in positions 2 and 4. Moreover, the calculations showed that the cross-metathesis of perfluoro- or perhaloalkenes should be a feasible process and that the metathesis is not very sensitive to stereochemical issues

Ru complexes of Hoveyda–Grubbs type immobilized on lamellar zeolites: activity in olefin metathesis reactions

• Hynek Balcar,
• Naděžda Žilková,
• Martin Kubů,
• Michal Mazur,
• Zdeněk Bastl and
• Jiří Čejka

Beilstein J. Org. Chem. 2015, 11, 2087–2096, doi:10.3762/bjoc.11.225

• cationic tags on NHC ligands were linker-free immobilized on the surface of lamellar zeolitic supports (MCM-22, MCM-56, MCM-36) and on mesoporous molecular sieves SBA-15. The activity of prepared hybrid catalysts was tested in olefin metathesis reactions: the activity in ring-closing metathesis of

• citronellene and N,N-diallyltrifluoroacetamide decreased in the order of support MCM-22 ≈ MCM-56 > SBA-15 > MCM-36; the hybrid catalyst based on SBA-15 was found the most active in self-metathesis of methyl oleate. All catalysts were reusable and exhibited low Ru leaching (<1% of Ru content). XPS analysis

• immobilization; olefin metathesis; Introduction Immobilization of Ru alkylidene complexes (Grubbs and Hoveyda–Grubbs type catalysts) on siliceous supports represents a successful way to highly active, selective, and reusable metathesis catalysts [1][2][3][4]. Mesoporous molecular sieves (MCM-41, MCM-48, SBA-15

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• metathesis, the evolution of metathesis catalysts towards air stability has become an area of significant interest. In this fascinating area of study, beginning with early systems making use of high oxidation state early transition metal centers that required strict exclusion of water and air, advances have

• been made to render catalysts more stable and yet more functional group tolerant. This review summarizes the major developments concerning catalytic systems directed towards water and air tolerance. Keywords: air stability; catalysis; olefin metathesis; RCM; ROMP; ruthenium; Introduction Transition

• metal-catalyzed alkene metathesis [1][2][3][4][5][6][7][8][9][10], which involves a fragment exchange between alkenes, is nowadays one of the most used strategies for the formation of carbon–carbon bonds. This area of study began with a “black box” approach for catalysts formation in polymerization of

Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• )-4,5-dihydroimidazol-2-ylidene). Catalysts 11 and 12 are additionally ligated by two pH-responsive DMAP ligands. The crystal structure was solved for complex 12 by X-ray diffraction. In organic, neutral solution, the catalysts are capable of performing standard ring-opening metathesis polymerization

• (ROMP) and ring closing metathesis (RCM) reactions with standard substrates. The ROMP with complex 11 is accelerated in the presence of two equiv of H3PO4, but is reduced as soon as the acid amount increased. The metathesis of phenylthiomethylidene catalysts 9 and 12 is sluggish at room temperature, but

• the polymerization process. Furthermore, the coagulate content for all experiments stayed <2%. This represents an unprecedented efficiency in emulsion ROMP based on hydrophilic ruthenium alkylidene complexes. Keywords: activation; aqueous catalysis; emulsion; olefin metathesis; polymerization

New aryloxybenzylidene ruthenium chelates – synthesis, reactivity and catalytic performance in ROMP

• Patrycja Żak,
• Szymon Rogalski,
• Mariusz Majchrzak,
• Maciej Kubicki and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2015, 11, 1910–1916, doi:10.3762/bjoc.11.206

• Grubbs catalysts bearing a triphenylphosphine ligand (or its para-substituted analogues) by metathesis exchange with substituted 2-vinylphenols. The complexes behave like a latent catalyst and are characterized by an improved catalytic behaviour as compared to that of the known analogues, i.e., they

• ) and a single selected norbornene derivative. Keywords: chemoactivation; latent catalysts; metathesis; ROMP; ruthenium; Introduction Olefin metathesis is nowadays one of the most important methods for the formation of carbon–carbon bonds in organic and polymer chemistry [1][2]. The availability of

• well-defined ruthenium-based catalysts, showing a number of desirable features such as tolerance of functional groups, moisture and air, has significantly expanded the scope and application of this process regardless of dynamic advancement in the development of ruthenium-based metathesis catalysts

Stereochemistry of ring-opening/cross metathesis reactions of exo- and endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles with allyl alcohol and allyl acetate

• Piotr Wałejko,
• Michał Dąbrowski,
• Lech Szczepaniak,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 1893–1901, doi:10.3762/bjoc.11.204

• are discussed. Surprisingly good yields of the ROCM products were obtained under neat conditions. Keywords: Grubbs’ catalysts; metathesis; ROCM; ROMP; Z-selectivity; Introduction Substituted tetrahydrofurans are a common motif found in many biologically active natural products [1][2], e.g

• -oxanorbornene) followed by cross metathesis with a cross partner (e.g., propene) to give the respective ring-opening cross metathesis (ROCM) products. Preliminary analysis suggested that these transformations lead mainly to incorporation of two molecules of a coupling partner, if present in excess, into

• -opening metathesis polymerization (ROMP) can be minimized by carrying out the reaction in high dilution. Furthermore good yields of ROCM products can be obtained only when an 1.5-fold excess of a cross olefin is used [14][19][20]. Results and Discussion Now, we wish to report our preliminary results of

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• Raphael Reuter Thomas R. Ward Department of Chemistry, University of Basel, Spitalstrasse 51, CH-4056 Basel, Switzerland 10.3762/bjoc.11.203 Abstract Herein we report on a 96-well plate assay based on the fluorescence resulting from the ring-closing metathesis of two profluorophoric substrates

• . To demonstrate the validity of the approach, four commercially available ruthenium-metathesis catalysts were evaluated in six different solvents. The results from the fluorescent assay agree well with HPLC conversions, validating the usefulness of the approach. Keywords: fluorescence; microplate

• screening; ring closing metathesis; Introduction Since its discovery in the 1950s, olefin metathesis has developed into one of the most powerful catalytic reactions both in research as well as in industrial applications [1][2][3]. This is mostly due to its excellent chemoselectivity, tolerance of many

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• Chemistry, Hlavova 2030, CZ-128 40 Prague, Czech Republic Faculty of Chemistry, University of Seville, E-41012 Seville, Spain 10.3762/bjoc.11.201 Abstract The cross metathesis of 1,2-epoxy-5-hexene (1) with methyl acrylate and acrylonitrile was investigated as an entry to the synthesis of polyfunctional

• compounds. The resulting cross metathesis products were hydrogenated in a tandem fashion employing the residual ruthenium from the metathesis step as the hydrogenation catalyst. Interestingly, the epoxide ring remained unreactive toward this hydrogenation method. The saturated compound resulting from the

• cross metathesis of 1 with methyl acrylate was transformed by means of nucleophilic ring-opening of the epoxide to furnish a diol, an alkoxy alcohol and an amino alcohol in high yields. Keywords: cross metathesis; epoxide; ruthenium catalysts; tandem reactions; Introduction Catalytic carbon–carbon