Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• –Grubbs catalyst) catalysed ring-closing metathesis gave dibenzo[b,f]heteropines 122 in excellent yields (>80%). Unfortunately, the metathesis reaction required elevated temperatures (>100 °C) and dilute solutions to reduce unwanted self-metathesis competing with RCM. While excellent yields for

• prepared by Wittig methylenation of commercially available bis(2-formylphenyl) ether (119), whereas a formylation–Wittig methylenation sequence of commercial diphenylsulfone (120) and protected bis(2-bromophenyl)amine 121 afforded the S- and N-tethered diene, respectively. Ruthenium (2nd generation Hoveyda

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• section on filtering metal catalysts [88]. One representative example was reported by Jensen and co-workers. The authors developed a nanofiltration device capable to retain and recycle the Hoveyda–Grubbs catalyst [125]. Interestingly, another vacuum Teflon membrane is used to remove the ethylene that is

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

• ethene atmosphere (A) Anhydrous dichloromethane was degassed and then percolated with ethene for several min. To the oxaenediyne (1 equiv) in CH2Cl2 was added the Grubbs or Hoveyda–Grubbs catalyst (0.05 equiv) in CH2Cl2 and the mixture was stirred under an ethene atmosphere at 25 °C for 24 h. Afterwards

• was degassed before reaction. To the oxaenediyne (1 equiv) in CH2Cl2 was added the Grubbs or Hoveyda–Grubbs catalyst (0.05 equiv) in CH2Cl2 and the mixture was stirred under an argon atmosphere at 25 °C for 24 h. Afterwards, the mixture was filtered through a short pad of silica, the silica washed

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

• , respectively, by domino metathesis reactions using the Hoveyda–Grubbs catalyst (4 mol %). In the final step, (−)‐clavukerin A was effectively converted into (+)-clavularin A and the latter epimerized to (−)-clavularin B. Recently, (–)-isoguaiene (11), a member of the guaiane sesquiterpenes and structurally

• combined an enyne ring-closing metathesis and an alkene cross-metathesis reaction in a sequential mode, using the appropriate enantiopure enynes and the Hoveyda–Grubbs catalyst in both transformations (Scheme 15). High yields and excellent chemoselectivities toward the diene products were attained in both

• the second-generation Hoveyda–Grubbs catalyst (5 mol %, 83% yield), under an ethylene atmosphere. The subsequent regioselective NaIO4-mediated oxidative cleavage of the pendant double bond, followed by the installation of the unsaturated N-butenyl group, oxidation, and deprotection provided the final

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• ; cross metathesis; Hoveyda–Grubbs catalyst; olefin metathesis; RCM; ring-closing metathesis; ring-opening cross metathesis; ROCM; ruthenium metathesis catalyst; styrene; 2-vinylbenzylamine; Introduction Ruthenium-catalysed olefin metathesis reactions have been playing an important role in various fields

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• leader sequence to the N-terminus of streptavidin (Sav) allowed the secretion and assembly of functional tetrameric Sav in the periplasm of E. coli. The passive diffusion of the biotinylated Hoveyda–Grubbs catalyst 60 through the outer membrane of E. coli containing Sav in its periplasm then affords the

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• and Ru-2 were synthesized in one step from the commercially available Hoveyda–Grubbs catalyst Ru-0 and the corresponding disodium dithiolate salts (Scheme 1). Initially, Hoveyda described the complexes Ru-1 and Ru-2 as Z-selective catalysts [2]. However, subsequent studies by Pederson and the Grubbs

• ). Then Hoveyda–Grubbs catalyst Ru-0 is added to generate after another 30 minutes a solution of the desired catalyst Ru-3. Finally, the ruthenium stock solution of Ru-3 is added to the alkene starting material (e.g., for the cross metathesis of 12 and 50) to give the product in high yields and excellent

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• ]. Today there are hundreds of examples of second generation Grubbs and Hoveyda–Grubbs catalyst derivatives bearing different NHCs to form specialized catalysts for metathesis [13][14]. An interesting attempt to further modify the electronic properties of NHCs is to introduce a charged moiety to form

• most feasible for medium and large-sized olefins (Scheme 5) [61][62]. Results presented in Table 4 suggest that the incorporation of cationic NHC increases the Gibbs free energy (∆G10) barriers by ca. 4–6 kcal/mol with respect to the standard Hoveyda–Grubbs catalyst (Hov) [63]. Given the accuracy of

• our computational methods, estimated at around 1–2 kcal/mol, we can expect that cationic Hoveyda-type catalysts are only slightly slower than the Hoveyda–Grubbs catalyst. This result is in agreement with experimental reports on various onium tag-modified systems [23][24] showing moderate activities of

Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

• Jacqueline Pollini,
• Valentina Bragoni and
• Lukas J. Gooßen

Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252

• of the entire mixture and subsequent selective precipitation of 6-(ω-nonenyl)salicylic acid from cold pentane. The olefinic side chain of this intermediate was elongated by its cross-metathesis with 1-hexene using a first generation Hoveyda–Grubbs catalyst, which was reused as precatalyst in a

• converted in high yields at 10 bar of ethylene in the presence of 0.5 mol % of the first generation Hoveyda–Grubbs catalyst Ru-1. The resulting mixture was filtered through celite, and the dichloromethane solvent was removed in vacuo. After addition of pentane, the mixture was chilled causing selective

• search for the optimal performance (Figure 1). The second generation Hoveyda–Grubbs catalyst previously used to change the olefinic side chain of cardanol via cross-metathesis [36], only reached a yield of 45% (Table 1, entry 17). Several modified second generation catalysts were tested, reaching yields

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• , 70.62; H, 7.10; N, 1.90. Synthesis of macrocyclic compound 25 To a solution of diene 24 (85.0 mg, 0.060 mmol) in degassed, anhydrous toluene (10 mL), Hoveyda–Grubbs catalyst 2nd generation (3.7 mg, 0.006 mmol) was added, and the mixture was stirred and heated at 95 °C for 48 h. The mixture was

• –Grubbs catalyst (II gen.) afforded the target macrocycle 25 in 26% yield (Scheme 4). The E-configuration of the newly created C=C-bond in the final product was proven by 1H NMR analysis (J15-15’ = 15.9 Hz). Conclusion In summary, we proposed an efficient method of the synthesis of a 31-membered

• from the C6’-position gave alcohol 22 in 97% yield. Under the same "Swern oxidation–reductive amination–acetylation" conditions, alcohol 22 was converted into aldehyde 23, which reacted further with amine 18, furnishing diolefin 24 in 64% total yield. Cyclization of precursor 24 induced by the Hoveyda

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• compound 9. This compound was synthesised by esterification of pent-4-en-2-ol (31) with acryloyl chloride (32) to 33, followed by ring-closing metathesis using the Hoveyda–Grubbs catalyst of the second generation (Scheme 8). The synthetic material proved to be identical to the volatile of D. clavata

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• for single-ring pyrrole derivatives [14][15] and, as shown in Scheme 4, they were uneventfully transformed into the target compounds 12 in the presence of the second-generation Hoveyda–Grubbs catalyst and copper(I) iodide. Interestingly, the reactions starting from 1-allylpyrroles gave a single

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• –Grubbs catalyst furnished a broad range of isomeric products, the (Z)-selective Grubbs catalyst lead to pure (Z)-products. Analysis by chiral GC revealed the natural frog compound to be (5Z,13S)-5-tetradecen-13-olide (1). This compound is also present in the secretion of other hyperoliid frogs as well as

• , the structure of another major component was suggested to be a tetradecen-13-olide. The synthesis of the two candidate compounds (Z)-5- and (Z)-9-tetradecen-13-olide revealed the former to be the naturally occurring compound. The synthesis used ring-closing metathesis as key step. While the Hoveyda

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

• ][49][50]. To date, only one example is reported where catalyst 15 is used in air (see following section). Hoveyda–Grubbs catalyst The next notable evolution in terms of higher catalyst stability came from the Hoveyda group in 1999 [51]. While performing metathesis in the presence of isopropoxystyrene

• this increased stability diminished the activity of 21 when compared to 15 [52]. In 2000, Dowden [53] and co-workers reported the use of a polystyrene-supported ruthenium complex 24 (Scheme 5); a variation of the Hoveyda–Grubbs catalyst. It could be reused up to 5 times without loss of activity and

• Grela group presented some variations of the Hoveyda–Grubbs catalyst 21 [52][59][60]. They reported some modifications to the isopropoxystyrene group; a nitro group para to the isopropoxy moiety of the carbene provided a much faster initiating catalyst (87, Figure 12) than 21, due to the weakening of

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 presence of second generation Hoveyda–Grubbs catalyst [23]. After the initial formation of the trienic unit, an intramolecular Diels–Alder reaction (IMDAR) rendered highly functionalized bicyclic derivatives in a very efficient manner. More recently, a multicomponent CEYM–intermolecular hetero

• performed by heating 1.0 equiv of phenylacetylene (1a) and 3.0 equiv of diolefinic ester 2a in toluene in the presence of second generation Hoveyda–Grubbs catalyst [Ru-II]. After 6 hours at 90 °C, bicyclic lactone 3a was obtained in 25% yield (Table 1, entry 1), together with lactone 4a (15%, arising from

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• Knapkiewicz et al. [37] (Scheme 11). The product 2-isopropoxy-5-nitrobenzaldehyde (37) is an intermediate to obtain a nitro-substituted Hoveyda–Grubbs catalyst. Scale-up based on the conventional batch approach yielded a higher extent of the undesired regioisomer 38 (37% rise than the laboratory scale batch

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

• generation Hoveyda–Grubbs catalyst generates a diene moiety which in situ reacts with a wide variety of dienophiles giving rise to a small family of new fluorinated carbo- and heterocyclic derivatives in moderate to good yields. This is a complementary protocol to the one previously described by our research

• generation Hoveyda–Grubbs catalyst I was heated under ethylene atmosphere (1 atm) for 2 h, the clean formation of diene 2a was observed. This newly formed diene was isolated in 70% yield and it reacted smoothly with 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione as dienophile at room temperature to afford, after

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

• /hydroboration/oxidation, which gave the best results when the Hoveyda–Grubbs catalyst 6 was used in the RCM (Scheme 15). Interestingly, in this case the asymmetric synthesis of the protected RCM precursor 78 started from a non-chiral source, the alcohol 75, and proceeded with complete stereocontrol over the 11

• hydride traps. Satisfactory results in RCM were, however, obtained from 78: in the presence of the 2nd-generation Grubbs catalyst 5 and benzoquinone in refluxing toluene, 78 was converted into the cyclized enol ether 79 in 70% yield, while with the Hoveyda–Grubbs catalyst (6, 10 mol %; benzoquinone 10 mol

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

• catalysts was reported [20]. A second generation Hoveyda–Grubbs catalyst was immobilized on silica without any linkers by simply placing the Ru complex in contact with silica in a suspension. Heterogeneous catalysts (loading from 0.05 to 0.6 wt % Ru) were prepared, which were active in ring-opening

• ) were obtained in high yields (70% and 64% for 3/MCM-41 and 3/SBA-15, respectively) after 3 h. The catalysts 3/MCM-41 and 3/SBA-15 exhibited some features similar to those of Hoveyda–Grubbs catalyst immobilized on silica [20]: (a) Filtration experiments proved complete catalyst heterogeneity only for

• led to high molecular weight polymers, whereas in [20] the formation of polymer was not referred. Interaction between the Ru complex and the support For Hoveyda–Grubbs catalyst immobilized on silica, the authors in [20] proposed a direct chemical interaction between the Ru species and the silanol

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

• -imidazolidinylidene)dichloro(2-(1-methylacetoxy)phenyl]methylene ruthenium(II) (Umicore, C3), (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene) ruthenium(II) (Hoveyda–Grubbs catalyst 2nd generation, C4, Sigma–Aldrich). General Methods Thin layer chromatography (TLC) was