Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• that a less-hindered olefin facilitated the second enyne metathesis of this tandem reaction. The same strategy was applied for the synthesis of the variecolin [5-8-6-5] skeleton (Scheme 20). Dienynes 112 and 113 were first prepared from methyl ketone 111 and subsecuently submitted to the metathesis

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• ., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic 10.3762/bjoc.16.226 Abstract The prochiral 4-(allyloxy)hepta-1,6-diynes, optionally modified in the positions 1 and 7 with an alkyl or ester group, undergo a chemoselective ring-closing enyne metathesis yielding racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H

• enantioselective enyne metathesis yielding chiral building blocks for compounds with potential biological activity, e.g., norsalvinorin or cacospongionolide B. Keywords: Diels–Alder reaction; enediyne; enyne metathesis; ring-closing metathesis; ruthenium precatalyst; Introduction Among the plethora of metathetic

• precatalysts [18][19][20] in the enantioselective RCM, however, the high air and moisture sensitivity makes their use less practical. The choice of the catalyst is one of the key elements in both cross and ring-closing enyne metathesis and the other is the substrate structure. Both of these factors determine

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• Paris, Palaiseau Cedex, France 10.3762/bjoc.16.79 Abstract A diversity-oriented synthesis (DOS) approach has been used to functionalize 17-ethynyl-17-hydroxysteroids through a one-pot procedure involving a ring-closing enyne metathesis (RCEYM) and a Diels–Alder reaction on the resulting diene, under

• ; ring-closing enyne metathesis; spirosteroids; steroids; Introduction Diversity-oriented synthesis (DOS) is a powerful approach to access collections of structurally diverse compounds in a few synthetic steps [1][2][3][4][5][6][7]. It can be more relevant when the chemical diversity is centred on

• the propargylic alcohol, the resulting enyne is a good substrate for ring closing enyne metathesis (RCEYM) towards new diene substrates [40][41][42], which can be employed in Diels–Alder reactions with a variety of dienophiles (Figure 1) [43][44][45][46][47][48][49][50][51][52][53][54]. This strategy

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• account surveys the current progress on the application of intra- and intermolecular enyne metathesis as main key steps in the synthesis of challenging structural motifs and stereochemistries found in bioactive compounds. Special emphasis is placed on ruthenium catalysts as promoters of enyne metathesis

• of known, in vivo effective substances but also for designing chemically modified analogs as valid alternatives for further therapeutic agents. Keywords: bioactive compounds; enyne metathesis; ring-closing metathesis; ruthenium catalysts; tandem reactions; Introduction Alkene and alkyne metathesis

• [44]. Among the various embodiments of olefin metathesis, the highly chemoselective enyne metathesis reaction [45][46][47][48][49] has led to some of the most striking advances in the development of modern, efficient synthetic protocols [50][51]. Thus, the present account focuses on the impressive

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• investigated with the objective of constructing condensed polycyclic structures. This investigation demonstrated that the generally observed domino reaction course involving a ring-opening metathesis of the norbornene unit and a ring-closing enyne metathesis is influenced to a great extent by the nature of the

• ][28][29][30][31][32][33] for the synthesis of a variety of complex ring systems such as condensed, bridged and spirocycles difficult to obtain otherwise. On the contrary, the domino process involving a ring-opening metathesis (ROM) followed by a ring-closing enyne metathesis (RCEYM) [34][35][36][37

• norbornene derivatives with an alkynyl side chain affording the major product arising from domino ROM–RCEYM while the enyne metathesis product was observed only in very low yield. In order to realize our objective and to find out if the free hydroxy group has any influence on the outcome of the metathesis

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• Diels–Alder reaction, Claisen rearrangement, cross-metathesis, and cross-enyne metathesis are used. The synergistic combination of these powerful reactions is found to be useful for the construction of complex targets and fulfill synthetic brevity. Keywords: Claisen rearrangement; Diels–Alder reaction

• a CM in an efficient manner. Biaryl derivatives In view of the interesting properties of biaryl derivatives, we have identified a three-step sequence, which involve cross-enyne metathesis (CEM), DA reaction followed by SM coupling [46]. To this end, acetylene derivatives 96a,b were subjected to CEM

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• ][17][18][19][20][21] and enyne metathesis [22][23]. We became interested in the cross-coupling of cyclic siloxanes in the context of preparing trisubstituted Z-styrenes for the synthesis of natural product targets [24]. Heliannuol A was the first member of a family of allelopathic [25][26][27

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

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

• related to the RRM readers may refer to excellent reviews available in the literature [3][4][5][6]. Review Cyclopropene systems Cyclopropene derivatives are highly strained systems and they are ideal candidates for the RRM process. In this context, Zhu and Shi [7] have reported the ring-closing enyne

• metathesis (RCEM) of small-rings such as cyclopropenes by employing the Grubbs’ first-generation (G-I) catalyst. They have reported a new tandem ROM–RCM–CM sequence starting with 1,6-cyclopropenynes 16 with a wide variety of substituted olefins. To this end, the required building block 16 has been prepared

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

• by HCl addition. The versatility of the catalyst was subsequently demonstrated in RCM, CM and enyne metathesis reactions. Solid-state structure of complex 4a from single crystal X-ray diffraction. Hydrogens have been omitted for clarity. (N in blue, C in grey, O in red, Cl in green). Olefin

• . Synthesis of complex 4a and 4b from (SIPr)(pyridine)RuCl2(indenylidene) (5). Substrate scope in RCM, CM and enyne metathesis catalyzed by 4aa. Supporting Information Supporting Information File 38: Full experimental procedures and detailed analytical data for ruthenium complexes. Acknowledgements This

Ruthenium indenylidene “1^st generation” olefin metathesis catalysts containing triisopropyl phosphite

• Stefano Guidone,
• Fady Nahra,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2015, 11, 1520–1527, doi:10.3762/bjoc.11.166

• higher catalytic activity was observed for Ind-I with 77% conversion when using 2 mol % pre-catalyst at 30 °C (Table 2, entry 13). Complex 1 was active in the ring-closing enyne metathesis (RCEYM) with 78% conversion of substrate 12 obtained with 1 mol % catalyst loading (Table 2, entry 14). A higher

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

• Abstract A new tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR) has been carried out. It involves conjugated ketones, esters or amides bearing a remote olefin and aromatic alkynes as the starting materials. The overall process enables the preparation of a small family of

• linear bicyclic scaffolds in a very simple manner with moderate to good levels of diastereoselectivity. This methodology constitutes one of the few examples that employ olefins differently than ethylene in tandem CEYM–IMDAR protocols. Keywords: bicyclic frameworks; cross enyne metathesis; Diels–Alder

• reaction; tandem reaction; Introduction Among all metathetic processes, the enyne metathesis reaction has received significant attention as an attractive and frequently used synthetic tool in organic synthesis [1][2][3][4][5][6][7]. It is an atom economical process that combines alkene and alkyne moieties

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

• [141] reported the synthesis of meta-cyclophane 145 at room temperature by ring-closing alkyne metathesis of 1,3-bis(3-pentynyloxymethyl)benzenes (Figure 9). This strategy has also been extended to ortho and para-derivatives. Cross-enyne metathesis: Recently, Kotha and Waghule [142] have synthesized

• diverse crownophanes by using a cross-enyne metathesis and Diels–Alder (DA) reaction as key steps. Here, the macrocycles 146 and 149 were subjected to a cross-enyne metathesis protocol with ethylene to generate the dienes 147 and 150, respectively. These dienes were subjected to a DA reaction with

• 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

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• phenanthridine core starting from a simple disubstituted aniline relied on the aza-Claisen rearrangement, ring-closing enyne metathesis and Diels–Alder reaction [41] (Scheme 18). The obtained phenanthridine derivatives were polysubstituted at the phenyl side-rings, while retaining the unsubstituted central

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

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

• Institut, Westfälische Wilhelms-Universität, Corrensstraße 40, D-48149 Münster, Germany 10.3762/bjoc.9.305 Abstract Propargylic difluorides 1 were used as starting substrates in a combination of cross-enyne metathesis and Diels–Alder reactions. Thus, the reaction of 1 with ethylene in the presence of 2nd

• for the creation of carbon–carbon bonds has exponentially increased, due to the availability of well-defined catalysts [1][2][3]. Particularly, enyne metathesis (EYM) is a powerful synthetic tool for generating 1,3-dienes by redistributing unsaturated functionalities between an alkene and an alkyne

• ]. The intramolecular version of this process, the ring closing enyne metathesis (RCEYM) reaction, has found wide application, and several examples can be found in the literature [12][13]. However, the intermolecular version, i.e. the cross-enyne metathesis (CEYM) reaction, has been much less exploited

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

• ) and related variants such as alkyne and enyne metathesis [36][37]. Related reactivity is prevalent for other Mδ+═Eδ− species such as imides and nitrides. Bergman's bis(cyclopentadienyl)zirconium(IV) imides, described above, will add alkenes and alkynes in [2 + 2] fashion across the Zr═NR bond (Scheme

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

• Olivier Debleds,
• Eric Gayon,
• Emmanuel Vrancken and
• Jean-Marc Campagne

Beilstein J. Org. Chem. 2011, 7, 866–877, doi:10.3762/bjoc.7.99

• been described by Fairlamb [82]. We were also able, from compound 2, to develop a 1,5-enyne metathesis that leads to functionalized cyclobutenes 38 (Scheme 20) [83], which was subsequently nicely illustrated by Goess in a total synthesis of grandisol [84]. From isoxazolines 23, we were also able to

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

• later Mori [22][23] utilized chromium alkoxycarbene to develop the first cyclizations via catalytic intramolecular enyne metathesis transformation. These initial works gave reason to postulate the interaction of metal carbene with alkyne to form a metallacyclobutene that rearranges to give a metal

• vinylcarbene (Scheme 1). This is the mechanistic basis of intramolecular enyne metathesis and EYCM reactions. In this review, we will focus on recent developments in EYCM transformations with ruthenium carbene catalysts [24][25][26][27][28][29][30][31][32]. This will include some general features on EYCM

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

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

• by the potentially labile natural product scaffold. Enhancement effects by an allylic hydroxy group have also been found in ring-closing enyne metathesis. Studies by Takahata et al. revealed that the ring-closing enyne metathesis of terminal alkynes containing an allylic hydroxy group proceeded

• efficient ring-closing enyne metathesis of the acyclic starting material as the key cyclization step. Associated mechanistic studies suggested that the reaction proceeded via an “ene-then-yne” pathway, further suggesting that rate acceleration is likely due to the directing effect of the allylic hydroxy

• ]. a) Acceleration of ring-closing enyne metathesis by the allylic hydroxy group [23]. b) Proposed mode of action by the allylic hydroxy group in this reaction. a) Effect of the hydroxy group on the rate and steroselectivity of ROCM [24]. b) Proposed H-bonded ruthenium complex for stereoselective ROCM

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

• (Table 2, entry 6). Ring closing enyne metathesis Imahori et al. have recently discovered that allylic hydroxy groups significantly enhance the rate of ring closing enyne metathesis reactions [53][54]. In these cases, addition of an ethylene atmosphere [55] which is normally considered to be mandatory

• for good results, is not required. We have recently investigated the highly selective enyne metathesis of substrates such as 5a,b to dihydropyrans 6a,b in the presence of first generation catalysts B and C [56]. Notably, no dihydrofurans or other isomers were observed. Sometimes, the selectivity

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

• 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

• The results presented indicate a slight activity change in various olefin metathesis reactions when changing the anionic co-ligands from chlorides to iodides. In general, the catalysts are good for RCM and enyne metathesis of moderately hindered substrates; however, they exhibit low activity towards

• catalyzing transformations of sterically hindered substances. The parent dichloro derivative 1 is the most active catalyst in every transformation studied. The diiodo derivative 3 is a slightly inferior catalyst in RCM, enyne metathesis and CM, but 3 is reluctant or even ineffective to initiate ROMP of

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

• difluorodihydropyridinones via a ring-closing metathesis reaction, and of 4,4-difluoro-3-oxoisoquinolines through a ring-closing metathesis–enyne metathesis tandem reaction. These products, in turn, undergo a Diels–Alder reaction to yield heterotricyclic systems in moderate to good yields. Keywords: bicyclic lactams

•  tricyclic ring systems [20]. Results and Discussion Initially, we investigated the enyne metathesis reaction of fluorinated enyne 1a with commercially available ruthenium carbene complexes, the Hoveyda–Grubbs second-generation catalyst being the most reactive (entries 1–3, Table 1). The reaction at 110 °C

• reaction time. The stereochemistry of 7a and 7b was determined by COSY and NOESY experiments. Recently, various tandem reactions with ruthenium complexes have become popular in organic chemistry because Ru(II) complexes are capable of catalyzing additional reactions [26][27]. Since our enyne metathesis