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

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• -membered ring lactones stagonolide E and curvulide A were synthesized using a bidirectional olefin-metathesis functionalization of the terminal double bonds. Key steps are (i) a site-selective cross metathesis, (ii) a highly diastereoselective extended tethered RCM to furnish a (Z,E)-configured dienyl

• planned to use a macrolactonization of precursor 7 as the cyclization step. For the synthesis of 7, a cross metathesis of 1 (or a protected derivative) with methyl vinyl ketone (8) was envisaged as the first step, followed by an esterification of the more distant OH group with vinylacetic acid (9). This

• on cross metathesis would most likely be inefficient and yield substantial amounts of double functionalized product (Scheme 3) [9]. We tested methyl vinyl ketone (8) as a cross-metathesis partner, and the recently described Umicore M51 initiator (A) [20][33][34], as well as Grubbs’ second generation

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• heteroarenes and unactivated arenes were unreactive. The mechanism is analogous to the one depicted for alkenes [106]. Last but not least, a completely different strategy used by S. Blechert et al. involved the cross-metathesis of terminal olefins with perfluoroalkylethylenes [108]. Thus, the reaction does not

Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

• Jungho Jun,
• Hyu-Suk Yeom,
• Jun-Hyun An and
• Seunghoon Shin

Beilstein J. Org. Chem. 2013, 9, 1724–1729, doi:10.3762/bjoc.9.198

• + 2 + 2] reactions with alkenes [6]. On the other hand, Shin and co-workers have adopted propiolic acids and alkynyl sulfones for formal enyne cross metathesis (f-EYCM) [5]. These examples allow for an effective alkyne–alkene coupling under mild reaction conditions (rt) with as little as 1.5 ~ 2 equiv

• = di-t-butyl-o-biphenylphosphine, JohnPhos) formed in situ was used as catalyst, the reaction was more efficient in chlorinated solvents rather than polar aprotic or aromatic hydrocarbon solvents (Table 1, entries 1–7). Contrary to the previous [4 + 2] cycloaddition, formal enyne cross metathesis or [2

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• allyl bromide, presumably because of high stabilization and strong steric shielding of the carbanionic center [26]. In fact, the importance of steric factors in the reactivity of trisphosphonate esters manifested in many reactions of α-alkyl-substituted trisphosphonates. Thus, attempted cross metathesis

• congested analogue 12e smoothly undergoes cross metathesis to give the desired trisubstituted olefin 32 in high yield (Scheme 15) [26]. In a similar sense, reduction of the trisphosphonate 12e with 9-borabicyclo[3.3.1]nonane (9-BBN) followed by standard oxidative workup afforded the primary alcohol 33 in

• . Reaction between tert-butylphosphaethyne and diethyl phosphite in the presence of sodium metal. Cross metathesis of trisphosphonates 12 with 2-methyl-2-butene and the Grubbs second-generation catalyst. Hydroboration–oxidation of trisphosphonates 12b,e. Reaction of 3-butyn-1-ylidenetrisphosphonate 15 with

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• result in an increase in the integration of protons from the TMS group, indicating that secondary cross-metathesis events along the polymer backbone were not occurring to any significant extent in this timeframe. This is consistent with previous reports of related cis-butene derived terminators that

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• organic chemists. The degenerative transfer of xanthates A longstanding challenge in organic synthesis has been the intermolecular creation of new carbon–carbon bonds starting with simple unactivated alkenes. The cross-metathesis constitutes at the present time one of the better solutions to this problem

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• homoallyl alcohol 16. The magnesium bromide diethyl etherate mediated allylation proceeded under substrate control and with complete diastereoselectivity [23][32]. Cross-metathesis of homoallyl alcohol 16 with the unit B derived acrylamide 17 provided the α,β-unsaturated δ-hydroxy carboxamide 18 (Scheme 2

• ). In order to bring about complete metathesis of 16, the acrylamide 17 had to be employed in 1.2-fold excess, which resulted in a contamination of the cross-metathesis product 18 with minor amounts of the homo-coupling product 23. The latter could not be separated by flash chromatography on this stage

• B was synthesized by the same convergent route as described for derivative 22. Homoallyl alcohol 27 [23] was reacted with the D-pentafluorophenylalanine derivative 26 in a cross-metathesis reaction in the presence of Grubbs II catalyst (Scheme 4). The resulting α,β-unsaturated δ-hydroxy carboxamide

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

•  5) [38]. This reaction is important for the hydroamination of alkynes by Cp2ZrX2 complexes, which proceeds through zirconium imido intermediates [39]. A similar [2 + 2] cycloaddition of symmetrical alkynes across a tungsten nitride is the initial step in Johnson's nitrile-alkyne cross metathesis

• into a phosphine/borane FLP [14]. Oxygen-atom extrusion from CO2 by a Ta(V) neopentylidene [27]. Oxygen-atom transfer from acetone at a Zr(IV) imide [28]. Alkyne cycloaddition at a Zr(IV) imide [38]. Nitrile-alkyne cross metathesis at a W(VI) nitride [40][41]. C–H and H–H addition across a zirconium(IV