Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• intramolecular conjugate addition. Three of these compounds (1–3) were obtained from the corresponding alcohols [19][20] in three steps: Mitsunobu reaction with NH-Boc-tosylate, followed by tosyl deprotection with magnesium, and finally two-directional cross metathesis with ethyl acrylate to install the desired

• chloroacetamide with thiourea gave the free amine [21], which was then protected with Boc anhydride. Finally, cross metathesis with ethyl acrylate furnished the desired compound 4 in 24% overall yield. Cyclisation reactions The first attempts at the tandem Boc-deprotection/bicyclisation of these substrates were

• % yield, and was followed by alkylation with an excess of allyl bromide to provide the desired triallyl species in 66% yield. Cross metathesis of 19 with ethyl acrylate was then performed. Fortunately, it proved to be possible to achieve some selectivity for different products by varying the catalyst used

Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• starting from commercially available pseudoephedrine amide 10. The syntheses of the bottom fragments 6a and 6b were achieved by applying the previously reported cross-metathesis reactions of readily available 20a,b with (2Z,4E)-methyl hexa-2,4-dienoate followed by silylation to provide 21a,b [39]. These

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• introduction of the appropriate side chain, cross-metathesis appeared to be the most versatile method, permitting access to many members of this family, both naturally occurring and analogues. Two types of metathesis processes, RCM and CM, can be thus advantageously intertwined in the synthesis of

• broussonetines. For instance, the syntheses of broussonetines C, D, M, O and P were completed by Falomir, Marco et al. [62][63] in a convergent, stereocontrolled way starting from commercial D-serine (55) as the chiral precursor and by applying the critical step of cross-metathesis (the first-ever synthesis of

• broussonetines O and P) (Scheme 11). The cross-metathesis reaction was promoted by the 2nd-generation Grubbs catalyst (5, in CH2Cl2, by heating under reflux in a N2 atmosphere for 24 h or by heating for 1 h at 100 °C under microwave irradiation). As expected in a cross-metathesis process, a mixture of three

Ene–yne cross-metathesis with ruthenium carbene catalysts

• Cédric Fischmeister and
• Christian Bruneau

Beilstein J. Org. Chem. 2011, 7, 156–166, doi:10.3762/bjoc.7.22

• organic and polymer chemistry. Enyne metathesis is a powerful catalytic reaction to access such structural domains. Recent advances and developments in ene–yne cross-metathesis (EYCM) leading to various compounds of interest and their intermediates, that can directly be transformed in tandem procedures

• , are reviewed in this article. In addition, the use of bio-resourced olefinic substrates is presented. Keywords: catalysis; cross-metathesis; enyne; fatty acid esters; ruthenium; Introduction The interaction of alkyne triple bonds with metal carbenes or metal vinylidene species was already known

• ethylene at room temperature [39][41][42]. When the substrates were not reactive under these mild conditions, cross-metathesis efficiency was improved by using higher ethylene pressure [43] or changing the ruthenium precursor to the second generation Grubbs catalyst II and adjusting temperature and

Olefin metathesis in nano-sized systems

• Didier Astruc,
• Abdou K. Diallo,
• Sylvain Gatard,
• Liyuan Liang,
• Cátia Ornelas,
• Victor Martinez,
• Denise Méry and
• Jaime Ruiz

Beilstein J. Org. Chem. 2011, 7, 94–103, doi:10.3762/bjoc.7.13

• ) or, more usefully, dendrimer encapsulation – ring closing metathesis (RCM), cross metathesis (CM), enyne metathesis reactions (EYM) – for reactions in water without a co-solvent and (ii) construction and functionalization of dendrimers by CM reactions. Keywords: dendrimer; green chemistry

Recent advances in the development of alkyne metathesis catalysts

• Xian Wu and
• Matthias Tamm

Beilstein J. Org. Chem. 2011, 7, 82–93, doi:10.3762/bjoc.7.12

• ][11]. Catalyzed by organotransition metal complexes, this reaction type creates new C–C triple bonds very simply via the Katz mechanism (Scheme 1) [12], based on which a series of different reaction types such as alkyne cross metathesis (ACM), ring-closing alkyne metathesis (RCAM), ring-opening alkyne

The intriguing modeling of cis–trans selectivity in ruthenium-catalyzed olefin metathesis

• Naeimeh Bahri-Laleh,
• Raffaele Credendino and
• Luigi Cavallo

Beilstein J. Org. Chem. 2011, 7, 40–45, doi:10.3762/bjoc.7.7

• Petrochemical Institute (IPPI), P.O. Box 14965/115, Tehran, Iran 10.3762/bjoc.7.7 Abstract In this study we have investigated computationally the origin of the cis–trans selectivity in the Ru-catalyzed cross metathesis (CM) of a prototype monosubstituted olefin, i.e., propene. Our calculations suggest that the

• origin of the preferential formation of trans-olefins is in the product release step, which prevents the initially formed cis-olefin from escaping the metal, and returns it to the reaction pool until the trans-olefin is formed. Keywords: cis–trans selectivity; cross metathesis; DFT calculations; olefin

• useful possibilities is cross metathesis (CM), see Scheme 1, since it opens the door to the formation of functionalized and/or higher olefins from simpler unsaturated building blocks. Such a wide potential explains why CM applications span from the production of raw materials [5][6] to advanced and

Hoveyda–Grubbs type metathesis catalyst immobilized on mesoporous molecular sieves MCM-41 and SBA-15

• Hynek Balcar,
• Tushar Shinde,
• Naděžda Žilková and
• Zdeněk Bastl

Beilstein J. Org. Chem. 2011, 7, 22–28, doi:10.3762/bjoc.7.4

• metathesis polymerization (ROMP) of cyclooctene, ring-closing metathesis (RCM) of diallylsilanes and several types of cross-metathesis reactions. High stability of catalysts, reusability and low Ru leaching were also reported. However, the mode of attachment of the Ru species on the silica surface was

The cross-metathesis of methyl oleate with cis-2-butene-1,4-diyl diacetate and the influence of protecting groups

• Arno Behr and
• Jessica Pérez Gomes

Beilstein J. Org. Chem. 2011, 7, 1–8, doi:10.3762/bjoc.7.1

• synthesis. An attractive, sustainable and selective (but as yet unused) method in the chemical industry is the oleochemical cross-metathesis with preferably symmetric functionalised substrates. The current study explores the cross-metathesis of methyl oleate (1) with cis-2-butene-1,4-diyl diacetate (2

• ) starting from renewable resources and quite inexpensive base chemicals. Results: This cross-metathesis reaction was carried out with several phosphine and N-heterocyclic carbene ruthenium catalysts. The reaction conditions were optimised for high conversions in combination with high cross-metathesis

• -metathesis selectivity under mild reaction conditions. These two cross-metathesis products can be potentially used as functional monomers for diverse sustainable polymers. Keywords: cross-metathesis; methyl oleate; monomer; polyester; renewable resources; Introduction In the last decade, olefin metathesis

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• hydroxy group in metathesis has been known for more than 10 years, and many organic chemists have taken advantage of this positive influence for efficient synthesis of natural products. Recently, the discovery of the rate enhancement by allyl sulfides in aqueous cross-metathesis has allowed the first

• examples of such a reaction on proteins. This led to a new benchmark in substrate complexity for cross-metathesis and expanded the potential of olefin metathesis for other applications in chemical biology. The enhanced reactivity of allyl sulfide, along with earlier reports of a similar effect by allylic

• chalcogen effect in protein modifications via olefin metathesis and the associated principles of cross-metathesis (CM) partner selection for reliable and efficient reaction on proteins are also highlighted. The effect of allylic hydroxy groups in olefin metathesis The activating effect of allylic hydroxy

The catalytic performance of Ru–NHC alkylidene complexes: PCy₃ versus pyridine as the dissociating ligand

• Stefan Krehl,
• Diana Geißler,
• Sylvia Hauke,
• Oliver Kunz,
• Lucia Staude and
• Bernd Schmidt

Beilstein J. Org. Chem. 2010, 6, 1188–1198, doi:10.3762/bjoc.6.136

• benzylidene complexes bearing a tricyclohexylphosphine or a pyridine ligand in ring closing metathesis (RCM), cross metathesis, and ring closing enyne metathesis (RCEYM) reactions is compared. While the PCy3 complexes perform significantly better in RCM and RCEYM reactions than the pyridine complex, all

• catalysts show similar activity in cross metathesis reactions. Keywords: homogeneous catalysis; N-heterocyclic carbenes; olefin metathesis; pyridine ligand; Ruthenium carbene complexes; Introduction Over the past two decades, the olefin metathesis reaction became one of the most important C–C-bond forming

• ][23] have been important achievements. These phosphine-free catalysts of the general type F sometimes show higher activities due to enhanced catalyst lifetimes and have often been applied in cross metathesis reactions [24]. An alternative approach to phosphine-free Ru-metathesis catalysts uses

New library of aminosulfonyl-tagged Hoveyda–Grubbs type complexes: Synthesis, kinetic studies and activity in olefin metathesis transformations

• Etienne Borré,
• Frederic Caijo,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2010, 6, 1159–1166, doi:10.3762/bjoc.6.132

• catalysts was investigated with various substrates in ring-closing metathesis of dienes or enynes and cross metathesis. The results demonstrate that these catalysts show a good tolerance to various chemical functions. Keywords: cross-metathesis; kinetic studies; olefin metathesis; RCM; ruthenium

• hour. In order to investigate potential substrate dependency, the activity of the five SIMes-catalysts 4a–e was evaluated in three different cross-metathesis (CM) reactions involving methyl acrylate, methyl vinyl ketone (MVK) and acrylonitrile as electro-deficient alkenes and the two electron-rich

• μL, 1 μmol, 0.01 M solution of catalyst). The reaction progress was monitored by the periodical acquisition of data over 1 h and the conversions were calculated from the integration of allylic protons signals of substrates and products. General Procedure for Cross-Metathesis Reactions: A Schlenk tube

About the activity and selectivity of less well-known metathesis catalysts during ADMET polymerizations

• Hatice Mutlu,
• Lucas Montero de Espinosa,
• Oĝuz Türünç and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2010, 6, 1149–1158, doi:10.3762/bjoc.6.131

• the isomerization of a number of allylic ethers and long chain aliphatic alkenes during RCM and cross metathesis [21]. In the context of ADMET, isomerization of a terminal to an internal olefin, followed by a productive metathesis step with a terminal olefin, would liberate an α-olefin, such as

• C1 to challenging substrates, such as diethyl di(methallyl)malonate in fluorinated aromatic hydrocarbon solvents, resulted in a remarkable enhancement of catalytic activity. Moreover, this approach was successfully extended to the RCM of natural products and the cross-metathesis formation of

Light-induced olefin metathesis

• Yuval Vidavsky and
• N. Gabriel Lemcoff

Beilstein J. Org. Chem. 2010, 6, 1106–1119, doi:10.3762/bjoc.6.127

• present developments in the use of light to expedite olefin ring-closing, ring-opening polymerisation and cross-metathesis reactions. Keywords: catalysis; light activation; olefin metathesis; photoactivation; photoinitiation; photoisomerisation; RCM; ROMP; ruthenium; tungsten; Introduction The metal

Cross-metathesis of allylcarboranes with O-allylcyclodextrins

• Ivan Šnajdr,
• Zbyněk Janoušek,
• Jindřich Jindřich and
• Martin Kotora

Beilstein J. Org. Chem. 2010, 6, 1099–1105, doi:10.3762/bjoc.6.126

• , Czech Republic 10.3762/bjoc.6.126 Abstract Cross-metathesis between allylcarboranes and O-allylcyclodextrins was catalyzed by Hoveyda–Grubbs 2nd generation catalyst in toluene. The corresponding carboranyl-cyclodextrin conjugates were isolated in 15–25% yields. Keywords: carborane; catalysis; cross

• -metathesis; cyclodextrin; ruthenium; Introduction Cross-metathesis of two different alkenes constitutes an efficient and powerful tool for synthesis of various unsymmetrically substituted alkenes. This procedure has found enormous application in organic synthesis of various types of molecules such as

• natural and biologically active compounds [1]. One of the key aspects of this methodology, which is responsible for a high cross-metathesis selectivity, is a proper choice of a suitable ruthenium catalyst [2][3]. Efficacy of the cross-metathesis procedure has prompted also us to investigate hitherto

Halide exchanged Hoveyda-type complexes in olefin metathesis

• Julia Wappel,
• César A. Urbina-Blanco,
• Mudassar Abbas,
• Jörg H. Albering,
• Robert Saf,
• Steven P. Nolan and
• Christian Slugovc

Beilstein J. Org. Chem. 2010, 6, 1091–1098, doi:10.3762/bjoc.6.125

• catalytic performance of the complexes in ring opening metathesis polymerisation, ring closing metathesis, enyne cycloisomerisation and cross metathesis reactions. Keywords: cross metathesis; olefin metathesis; RCM; ROMP; ruthenium; Introduction Since the pioneering reports on the utilisation of N

• substrates are transformed. The lack of reactivity data for halide-exchanged complexes prompted us to investigate the catalytic activity of bromo and iodo analogues of Hoveyda 2nd generation catalyst (1) in ring closing metathesis (RCM), enyne metathesis and cross metathesis (CM). Moreover, the scope of

• before the remaining monomer is completely consumed. RCM, enyne cycloisomerisation and cross metathesis Catalytic activities of 1, 2 and 3 were then evaluated in RCM of diethyl diallylmalonate (7). The reaction progress is shown in Figure 6 (for details see Table 3). While 1 and 2 perform equally, 3 is

Gelation or molecular recognition; is the bis-(α,β-dihydroxy ester)s motif an omnigelator?

• Peter C. Griffiths,
• David W. Knight,
• Ian R. Morgan,
• Amy Ford,
• James Brown,
• Ben Davies,
• Richard K. Heenan,
• Stephen M. King,
• Robert M. Dalgliesh,
• John Tomkinson,
• Stuart Prescott,
• Ralf Schweins and
• Alison Paul

Beilstein J. Org. Chem. 2010, 6, 1079–1088, doi:10.3762/bjoc.6.123

• thermal history of the sample, but not the gelation mechanism. Experimental Materials All solvents were of spectroscopic grade and used as received. Synthesis of gelators The omnigelator 4 was prepared as previously described [52] by sequential Grubbs double cross metathesis [53] between (Z)-cyclodecene

• using d7-isopropyl acrylate (5) in the initial cross metathesis step. The deuterated ester 5 was prepared from acryloyl chloride and d7-isopropanol (Et3N, CH2Cl2, 0→20 °C, 2 h); yields were essentially identical to the nondeuterated example, given that the deuterated acrylate 5 was carefully purified

Synthesis of fluorinated δ-lactams via cycloisomerization of gem-difluoropropargyl amides

• Satoru Arimitsu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2010, 6, No. 48, doi:10.3762/bjoc.6.48

• reaction of fluorinated 1,7-enynes does not permit substitution at the 6-position of the resultant gem-difluoroisoquinolinone (eq 1, Scheme 2), we examined a potential cross metathesis–enyne metathesis tandem-type reaction (CM–EYM reaction). In theory, if the terminal vinyl group of diene 2 can be modified

Three step synthesis of single diastereoisomers of the vicinal trifluoro motif

• Vincent A. Brunet,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2009, 5, No. 61, doi:10.3762/bjoc.5.61

• following the procedure of Marinelli [14]. The tosyl ester 3 was then submitted to two cross-metathesis reactions using the Grubbs II catalyst and with an excess of either hexene or allyl benzene (5 equiv) to form allylic alcohols (S)-4 and (S)-5 respectively [15]. The excess of alkene favours the cross

• metathesis reaction and the products were obtained in good yields predominantly as the (E)-isomer. It was not possible to separate the minor (Z)-isomer at this stage, however isomer separation was more readily achieved after the subsequent epoxidation step. Thus (S)-4 and (S)-5 were subjected to epoxidation

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• -metathesis played a key role (Scheme 39) [99]. The bis-THF core unit 289 was constructed through a bidirectional outside-in hydroxy mesylate cascade cyclization route from 288. The bisbutenolide analogue 292 was prepared from diene 290 and the butenolide segment 291 through Grubbs cross-metathesis. Reaction

• allylsilane 285 mediated by SnCl4 afforded the bis-THF 286. Finally, the butenolide ring was installed using a procedure developed by Marshall’s group [96] to provide synthetic (+)-asimicin. In 2006, Marshall’s group reported the total synthesis of asimicin by a highly convergent route in which Grubbs cross

Total synthesis of the indolizidine alkaloid tashiromine

• Stephen P. Marsden and
• Alison D. McElhinney

Beilstein J. Org. Chem. 2008, 4, No. 8, doi:10.1186/1860-5397-4-8

• centres on the stereoselective construction of the indolizidine core by capture of an electrophilic acyliminium species by a pendant allylsilane. The key cyclisation precursor is constructed using olefin cross-metathesis chemistry, which has the potential to facilitate both racemic and asymmetric

• approaches, depending upon the choice of the allylsilane metathesis partner. Results The use of the allyltrimethylsilane cross-metathesis approach enables the rapid construction of the key cyclisation precursor 3 (3 steps from commercial materials), which undergoes acid-induced cyclisation to give the

• and their cross-metathesis reactions studied as part of a putative asymmetric approach to tashiromine. In the event, α-hydroxysilane 12 underwent isomerisation under the reaction conditions to acylsilane 17, while silanes 14 and 15 were unreactive towards metathesis. Conclusion A concise

Combining two-directional synthesis and tandem reactions, part 11: second generation syntheses of (±)-hippodamine and (±)-epi-hippodamine

• Annabella F. Newton,
• Martin Rejzek,
• Marie-Lyne Alcaraz and
• Robert A. Stockman

Beilstein J. Org. Chem. 2008, 4, No. 4, doi:10.1186/1860-5397-4-4

• -hippodamine are presented which are able to shorten the syntheses by up to two steps. Conclusions Key advances include a two-directional homologation by cross metathesis and a new tandem reductive amination / double intramolecular Michael addition which generates 6 new bonds, 2 stereogenic centres and two

• symmetrical dialkene similar to 4 using cross-metathesis with acrylonitrile was possible using the Hoveyda modification of Grubbs second generation catalyst [12] (Scheme 2). Thus, it seemed a logical extension of this thinking to see if we could carry out a direct double homologation of dialkene 4 with ethyl

• acrylate as the cross-metathesis coupling partner. In fact, due to the non-co-ordinating nature of ethyl acrylate (in comparison to acrylonitrile) and the inert phthalimide group, this reaction proved to be an outstanding success, delivering diester 6 in 88% yield over one step after a five day reaction in

Desymmetrization of 7-azabicycloalkenes by tandem olefin metathesis for the preparation of natural product scaffolds

• Wolfgang Maison,
• Marina Büchert and
• Nina Deppermann

Beilstein J. Org. Chem. 2007, 3, No. 48, doi:10.1186/1860-5397-3-48

• , if the generated exocyclic double bond in the RORCM product is susceptible to olefin cross metathesis with the small amount of styrene that is derived from the precatalyst 1. These types of products are favored, if additional olefins are added as CM partners. With addition of 3 equivalents styrene

• and 12. A sequence of ring opening and cross metathesis is extremely efficient for desymmetrization of 7 and 12 as depicted in Scheme 4 for the synthesis of isoindole 19 and the disubstituted pyrrolidine 20. In these cases, catalyst loadings can be low and yields are excellent. Unfortunately the ROCM

• of 7-azabicycloalkenes appeared to be quite sensitive with respect to the olefin cross metathesis partner [67] and we have not been able to transfer this reaction to α-substituted olefins like 21 yet. A more successful attempt to introduce selectivity, was the enantioselective catalytic