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

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

• 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

• allow the use of primary and secondary amines in ring-closing metathesis (RCM) and cross-metathesis (CM), and one of them is the transformation of amines into carbamates, amides or sulfonamides [27][28][29]. As an alternative, metathesis reactions can be performed with olefins possessing ammonium salts

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

• 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

• alkenes to hydrofluoroalkenes. Moreover, just recently a successful cross metathesis of perfluoroalkenes with vinyl ethers has been published [35]. The reported computations dealing with the metathesis of fluoroalkenes are also extremely scarce. Thus, the mechanism of the cross metathesis of norbornene

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

• of 1,7-octadiene and (−)-β-citronellene; HGIIN+Cl− on SBA-15 (HGIIN+Cl−/SBA-15) was the most active (TON up to 16000 in RCM of citronellene). HGIIN+Cl−/SBA-15 proved its versatility in RCM, enyne metathesis, metathesis of methyl oleate, and cross-metathesis of electron deficient methyl acrylate with

• -trifluoroacetamide (DAF), and (ii) in self-metathesis and cross-metathesis of methyl oleate. Lamellar (two dimensional) zeolites represent a subgroup of zeolitic materials, in which one of the dimension of the crystals is usually limited to 2–3 nm and is around one unit cell [24][25]. Depending on the structure of

• . The cumulative TON achieved in 7 runs was 1491. The results evidence very firm attachment of catalytically active species to the surface of zeolites and their good stability. Catalyst activity in self-metathesis and cross-metathesis of methyl oleate Conversion curves for self-metathesis of methyl

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

• reactions of tri- and tetrasubstituted olefins [42][46], cross-metathesis (CM) to afford trisubstituted olefins [44] and CM and RCM reactions of electron-withdrawing substituted olefins [45]. In comparison to the 1st generation, they show a generally higher stability towards thermal degradation [41][42][43

• retained the properties of stability and recyclability. In 2002, Hoveyda et al. reported the Hoveyda–Grubbs’ 2nd generation type catalyst 36 (Figure 3) [56]: Complex 36, bearing an unsymmetrical and chiral NHC, was active in the asymmetric ring-opening cross-metathesis (RO/CM) in air using undistilled

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

• have also been independently studied by Skowerski and Grela [10]. Phenoxybenzylidene complexes have been demonstrated to behave like latent catalysts in common testing reactions involving ring opening metathesis polymerisation (ROMP) of COD, norbornene derivative and dicyclopentadiene as well as cross

• metathesis (CM) of allylbenzene with Z-1,4-(diacetoxy)but-2-ene [9][10]. Although catalysts 1a–d are characterized by a number of advantages, they are not free from some weaknesses. They showed in some reactions a non-negligible catalytic activity in the absence of activators [9][10] and an instability of

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

• -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

• chromatograms recorded from crude reaction mixtures described in Table 1: a) entry 1 and b) entry 5. Numbering of carbon atoms in cross metathesis products. ROCM reactions of 7-oxanorbornene. Metathesis products of exo- and endo-7-oxabicyclo[2.2.1]hept-5-en-2-carbonitriles (1 and 2) with allyl acetate (3) or

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

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• decades have changed the landscape of organic synthesis. Armed with these advances, olefin metathesis has become a staple in retrosynthesis. Metathesis protocols such as ring-closing metathesis (RCM), cross-metathesis (CM), and enyne metathesis (EM) have gained popularity in the synthesis of complex

• skeletally diverse bi-, and tricyclic sultam derivatives (sulfonamide analogs) using norbornenyl sultam 272 as a core unit assembled by an intramolecular Diels–Alder (IMDA) reaction via a domino ROM–RCM–CM cascade. Diversity has been incorporated by using various cross-metathesis partners (Scheme 56). Basso

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• Iodide-containing nitro-Grela-type catalysts have been synthesized and applied to ring closing metathesis (RCM) and cross metathesis (CM) reactions. These new catalysts have exhibited improved efficiency in the transformation of sterically, non-demanding alkenes. Additional steric hindrance in the

• Hoveyda-type complexes in cross metathesis of methyl oleate with ethylene [16]. Complexes containing iodide lead to products of asymmetric OM with better enantio- and diastereoselectivity, but this came at the price of lower activity [17]. In the past few years the replacement of chloride ligands created

Cross-metathesis of polynorbornene with polyoctenamer: a kinetic study

• Yulia I. Denisova,
• Maria L. Gringolts,
• Alexander S. Peregudov,
• Liya B. Krentsel,
• Ekaterina A. Litmanovich,
• Arkadiy D. Litmanovich,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2015, 11, 1796–1808, doi:10.3762/bjoc.11.195

• Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova str. 28, 119991 Moscow, Russia Chemistry Department, Moscow State University, Leninskie gory 1, build. 3, 119991 Moscow, Russia 10.3762/bjoc.11.195 Abstract The cross-metathesis of polynorbornene and polyoctenamer in d

• cis-cyclooctene because of their substantially different monomer reactivities. Keywords: cross-metathesis; 1st generation Grubbs’ catalyst; interchange reactions; kinetics; multiblock copolymer; Introduction A desired sequence of monomer units in a polymer chain can be achieved not only in the

• the studies were focused on the intramolecular reactions [6][7] and polymer degradation by interaction with olefins [8][9], whereas the interchain cross-metathesis was merely an idea for many years [10]. Only recently a few publications appeared that demonstrated the possibility of using the Grubbs

Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

• Thibault E. Schmid,
• Florian Modicom,
• Adrien Dumas,
• Etienne Borré,
• Loic Toupet,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 1541–1546, doi:10.3762/bjoc.11.169

• -diisopropylphenyl)imidazolidin-2-ylidene) demonstrated excellent latent behaviour in ring closing metathesis (RCM) reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis reactions

• in model ring closing metathesis and cross-metathesis transformations. Results and Discussion With the objective to develop an attractive strategy for the synthesis of indenylidene-picolinic ruthenium complexes, we initially attempted their preparation using a silver-free methodology. In fact, silver

• % isolated yields, respectively. Finally, the cross metathesis reaction between allylbenzene and ethyl acrylate afforded the desired internal E-olefin with 62% yield. Conclusion We described the synthesis and characterization of three novel latent 2nd generation indenylidene-based precatalysts for olefin

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• the corresponding triene intermediate, which would evolve under the reaction conditions through the cycloaddition event to render the final products (Scheme 1). Results and Discussion The use of 1,5-, 1,6- and 1,7-dienes in cross metathesis-type transformations is not trivial since chemoselectivity

Cross-metathesis reaction of α- and β-vinyl C-glycosides with alkenes

• Ivan Šnajdr,
• Kamil Parkan,
• Filip Hessler and
• Martin Kotora

Beilstein J. Org. Chem. 2015, 11, 1392–1397, doi:10.3762/bjoc.11.150

• Praha 6, Czech Republic 10.3762/bjoc.11.150 Abstract Cross-metathesis of α- and β-vinyl C-deoxyribosides and α-vinyl C-galactoside with various terminal alkenes under different conditions was studied. The cross-metathesis of the former proceeded with good yields of the corresponding products in

• ; catalysis; carbohydrates; cross-metathesis; ruthenium; Introduction Natural and unnatural C-substituted glycosides are important compounds with a plethora of attractive biological properties and they often have been used as artificial DNA components [1]. Among various synthetic procedures providing C

• corresponding vinyl α-C-deoxyriboside α-2 and β-C-deoxyriboside β-2 [16]. As far as further transformation of vinyl C-deoxyribosides relying on the metathesis reaction is concerned, only one paper dealing with successful cross-metathesis with 4-vinyl-5-methyl-2-oxazolone has been reported [16]. This finding is

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• different dienophiles followed by aromatization which gave the crownophanes (e.g., 148 and 151) (Scheme 22). Cross metathesis: In 1992, (−)-cylindrocyclophane A (156) and (−)-cylindrocyclophane F (155) were isolated by Moore and co-workers [143] from a blue-green algae belonging to Cylindrospermum

• was subjected to dimerization involving cross-metathesis with G-I/G-II/Schrock catalysts which generated the cyclized product 154. Subsequently, hydrogenation of the cyclophane 154 followed by minor functional group modification gave the natural products 155 and 156 (Scheme 23). Furthermore, the same

• followed by cross metathesis. The molecule shows a hypsochromic shift which indicates rigidity in the molecule compared with the other linear molecules. Enyne metathesis: In 1998, Fürstner and co-workers [147] have employed platinum(II)-catalyzed enyne metathesis as a key step to form cyclophane ring

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• of vinyl-terminated SAMs has been demonstrated, e.g., through surface modification of radicals generated by C–O bond thermolysis [17] and in a more controlled sense via olefin cross metathesis/enyne metathesis [18] of mixed vinyl and acetylenyl-terminated SAMs followed by Diels–Alder modifications of

A modular phosphate tether-mediated divergent strategy to complex polyols

• Paul R. Hanson,
• Susanthi Jayasinghe,
• Soma Maitra,
• Cornelius N. Ndi and
• Rambabu Chegondi

Beilstein J. Org. Chem. 2014, 10, 2332–2337, doi:10.3762/bjoc.10.242

• ) and cross metathesis (CM) steps of the process as outlined in Scheme 1. This protocol further highlights the utility of phosphate tether mediated desymmetrization of C2-symmetric 1,3-anti-diene-diol subunit to generate polyol scaffolds which would otherwise be difficult to produce via (Z)-and (E

• and subsequent LiAlH4 reduction to generate tetraol 17 in 24% yield over 4 reaction steps in a two-pot operation (70% avg/rxn) (Scheme 3). Further, starting with the same triene 6, which was previously used in Scheme 2, but utilizing a different cross-metathesis partner (homoallylic alcohol 4), a

Relay cross metathesis reactions of vinylphosphonates

• Raj K. Malla,
• Jeremy N. Ridenour and
• Christopher D. Spilling

Beilstein J. Org. Chem. 2014, 10, 1933–1941, doi:10.3762/bjoc.10.201

• Raj K. Malla Jeremy N. Ridenour Christopher D. Spilling Department of Chemistry and Biochemistry, University of Missouri St. Louis, One University Boulevard, St. Louis, MO 63121, USA 10.3762/bjoc.10.201 Abstract Dimethyl (β-substituted) vinylphosphonates do not readily undergo cross metathesis

• reactions with Grubbs catalyst and terminal alkenes. However, the corresponding mono- or diallyl vinylphosphonate esters undergo facile cross metathesis reactions. The improved reactivity is attributed to a relay step in the cross metathesis reaction mechanism. Keywords: centrolobine; metathesis; organo

• . Unlike the parent compound, vinylphosphonates substituted with an aryl or alkyl group on the alkene appear to have somewhat limited reactivity. This lack of reactivity is exemplified by the Grubbs cross metathesis reaction [10]. Grubbs and co-workers classified terminal vinylphosphonates as type III

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• etherification, thiol-ene reaction and in particular olefin cross metathesis. Keywords: amphiphilic glycomimetics; cross metathesis; glycodendrons; multivalent glycoconjugates; multivalent glycosystems; Introduction In addition to nucleic acids and proteins, molecular life is based on a third important class

• , respectively, in fair yields. Deprotection conditions employing TFA in water left the thioethers intact. These results were encouraging for further postsynthetic modification of glycodendrons. In a second part of our study we have investigated olefin cross metathesis [11] of polyether di- and tetravalent

• ). Conclusion In conclusion, it was shown that readily available polyether glycodendrons can be refined employing suitable postsynthetic modification of the focal point. We have illustrated, that alkylation, thiol-ene reaction and in particular olefin cross metathesis leads to di- and tetravalent glycolipid

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• derivatization as well as for solid-phase peptide synthesis. With respect to according motifs occurring in natural products, we have converted these building blocks into 3-O-acylated structures. Utilizing an esterification and cross-metathesis protocol, (2S,3S)-3-hydroxyleucine derivatives were synthesized, thus

• opening up an excellent approach for the synthesis of bioactive natural products and derivatives thereof for structure activity relationship (SAR) studies. Keywords: chiral pool; cross metathesis; esterification; β-hydroxy-α-amino acids; natural products; Introduction Besides the proteinogenic β-hydroxy

• develop a method for the modification of the acyl side chain of a previously incorporated O-acylated β-hydroxy-α-amino acid building block at a very late stage and under mild conditions, e.g., by olefin cross metathesis. Therefore, amino alcohol 5 was Fmoc-protected (product 34, 84% yield), followed by

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• Bernd Schmidt Sylvia Hauke Institut für Chemie, Organische Synthesechemie, Universität Potsdam, Karl-Liebknecht-Straße 24–25, 14476 Potsdam-Golm, Germany 10.3762/bjoc.10.102 Abstract Cross metathesis of a lactate derived allylic alcohol and acrolein is the entry point to a de novo synthesis of 4

• L-amicetal 4 [36]. Alternatively, we have used 2 as a substrate for a cross metathesis reaction with methyl acrylate under isomerization-free conditions to furnish enoate 5, which underwent cyclization to the lactone 6 after hydrogenation. Reduction of 6 with DIBAL-H eventually yields a protected L

• -amicetose 7 [35]. To avoid the last step of the sequence, we envisaged a cross metathesis with acroleine, rather than methyl acrylate, to give enal 8 which should undergo spontaneous lactol formation after hydrogenation and desilylation. However, compared to cross metathesis reactions with methyl acrylate

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• Dess–Martin oxidation, Pinnick oxidation and methylation. Methyl ester 12 was obtained in 10 steps with a good overall yield of 20%. Olefin cross metathesis of alkene 12 with crotonaldehyde in the presence of a second generation Grubbs catalyst required only a short filter column to isolate α,β

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• cycloadditions better known as “copper mediated Click-chemistry” while alkenes, especially vinyl- and allylbenzoic systems, are predestined for being utilized in cross metathesis reactions. Therefore a series of aminobenzoic acids 9–20 (Figure 1) were prepared (see Supporting Information File 1). We expected

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• based on a first Diels–Alder cycloaddition, as shown above. However, a recent report of Norsikian, Beau and co-workers described a novel sequence of tandem transformations which combined the Petasis reaction, intramolecular [4 + 2]-cycloaddition, cross metathesis and Michael reaction. This process gave

One-pot cross-enyne metathesis (CEYM)–Diels–Alder reaction of gem-difluoropropargylic alkynes

• Santos Fustero,
• Paula Bello,
• Javier Miró,
• María Sánchez-Roselló,
• Günter Haufe and
• Carlos del Pozo

Beilstein J. Org. Chem. 2013, 9, 2688–2695, doi:10.3762/bjoc.9.305

• group, which involved the use of 1,7-octadiene as an internal source of ethylene. Keywords: cross metathesis; Diels–Alder; one-pot reaction; organo-fluorine; propargylic difluorides; Introduction In recent years the number of applications of olefin metathesis as a mild and competitive synthetic method

• . Thus, although a tandem-multicomponent protocol is more desirable, the use of the one-pot protocol expand the utility and scope of this methodology, since milder conditions can be employed in the cyclization step. Conclusion In conclusion, a tandem one-pot enyne-cross metathesis-Diels–Alder reaction of