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

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• synthesis of 1,2-oxaphosphaheterocycle 2-oxides. tert-Butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoate (11) generated tert-butyl 2-(allyloxy)-3,4,7-trihydro-1,2-oxaphosphepine-3-carboxylate 2-oxide (12) in excellent 94% yield in the presence of the Grubbs catalyst in DCM. After further allylation with allyl

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• the authors consisted in the ring closure through a metathesis reaction using the Grubbs catalyst [52][53]. The required compound 99 was prepared by converting compound 16 into the styrene 98 via a Wittig reaction followed by a transesterification to yield the desired allylic ester. Several reaction

• conditions for the metathesis using the 1st generation Grubbs catalyst were attempted without success, but when 2nd generation catalyst was used, the dimerization product 100 was observed (Scheme 20). Despite the yield for macrolide formation, Cousin proposed alternatives for the formal synthesis of 2

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

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• employed Stewart–Grubbs catalyst 71 is completely decomposed but its decomposition products could efficiently be removed by passing the reaction mixture through a cartridge containing a mixture of silica and charcoal providing 72 in 32% yield at a productivity of 0.2 g/h. The macrocycle 72 was already

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• ) was degassed with nitrogen for 15 min. After adding the Grubbs’ catalyst (15 mol %), the stirring was continued for 12 h at the same temperature. Next, the solvent was removed under reduced pressure followed by silica gel column chromatography (5% EtOAc/petroleum ether) provided the required product 6

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• second generation Grubbs catalyst 57 in 99% yield. The azabicyclic system (+)-51 underwent dihydroxylation with the OsO4-NMO system to form diol (+)-52 as the only product in 97% yield. Diol (+)-52 was regioselectively protected in the presence of tert-butyldimethylsilane triflate, and triethylamine

• , MeCN, 4A MS, rt, 80%; iii) HC≡CLi.H2NCH2CH2NH2 (5 equiv), THF, 40 °C, 88%; iv) HCl/MeOH, then HC(OMe)3, 93%; v) Lindlar catalyst, H2, MeOH, 92%; vi) Grubbs catalyst 57 (0.15 equiv), benzene, 50 °C, 99%; vii) OsO4, NMO, MeCN/H2O, 97%; viii) TBDMSOTf, Et3N, CH2Cl2, 98%; ix) 1. CS2, NaH, MeI, THF; 2. AIBN

• -carboxaldehyde, 9:1 77a/77b, 67% (after chromatographic separation); ii) butyl vinyl ether, Hg(OAc)2, (10 mol %), sealed tube, 130–135 °C, 79%; iii) vinylmagnesium bromide, −78 °C; iv) Dess–Martin periodinane, 83% over two steps; v) Grubbs catalyst 2nd gen., CH2Cl2, reflux, 74%; vi) 1. (PhSe)2, NaBH4, EtOH; 2

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

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• 21, was unsuccessful and no tricyclic product was formed. Bonnet-Delpon and co-workers reported the one-pot synthesis of several CF3-containing N-tethered amines in good yields (54–86% over 2 steps) [49]. These products were subjected to metathesis reactions in the presence of Grubbs catalyst

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

• Stewart–Grubbs catalyst combined with microwave heating at 120 °C (allyl ethers) or 170 °C (4-pentenyl ethers), demonstrating improved yields [77]. These temperatures were needed for the reaction to quickly go to completion. With 17-O-allylmestranol (5a), a rapid screening of the Stewart–Grubbs (SG

• . Synthesis of spirocyclic steroid derivatives by the RCEYM reaction. Conditions: (a) NaH (2 equiv), allyl or 4-pentenyl bromide (2 equiv), DMF, 0 °C→rt; (b) Second-generation Grubbs catalyst (G-II), toluene, under microwave at 120 °C (5a, 6a, 7) or 170 °C (5b, 6b). One-pot RCEYM/Diels–Alder reaction 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

• metathesis in tandem with a diene cross-metathesis as the crucial steps were reported by Lee in the total synthesis of (−)-amphidinolide E (3) (Scheme 6) [70]. It is noteworthy that the second-generation Grubbs catalyst was quite active and stereoselective for both the enyne and cross-metathesis steps

• , 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

• related to the trinorsesquiterpene (−)‐clavukerin A, was also communicated by Metz et al. [79] using an enyne metathesis reaction as a key step. The authors performed a relay metathesis of the trienyne or diene–diyne precursors in the presence of the second-generation Grubbs catalyst (Scheme 14). The

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

Remarkable effect of alkynyl substituents on the fluorescence properties of a BN-phenanthrene

• Alberto Abengózar,
• David Sucunza,
• Patricia García-García and
• Juan J. Vaquero

Beilstein J. Org. Chem. 2019, 15, 1257–1261, doi:10.3762/bjoc.15.122

• -generation Grubbs catalyst to yield dihydro-BN-phenanthrene 4, which was oxidized to 1b under the conditions previously optimized for the synthesis of the parent BN-phenanthrene 1a [23]. Next, we explored the preparation of various substituted BN-phenanthrenes by means of palladium-catalyzed cross-coupling

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• ylide 21 [8] followed by alkyne generation [23] with butyllithium in a one-pot process, trienyne 3 was obtained as a 1.6:1 mixture of E and Z olefin isomers. Due to the presence of the isopropyl group at the disubstituted alkene [24] of 3, 30 mol % of the second generation Grubbs catalyst 22 were

• ketone 20, the one-pot conversion of ketone 28 by olefination with unsaturated ylide 21 and alkyne formation with butyllithium yielded dienediyne 8 as a 1.3:1 mixture of E and Z olefin isomers. Gratifyingly, treatment of 8 with 25 mol% of the first generation Grubbs catalyst 29 produced the desired

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

• ). This would enable a rational selection of the optimal catalysts for specific metathesis reactions. It should be mentioned here that the idea of replacing the oxygen atom with nitrogen in the Grubbs catalyst is not new but only a limited number of examples are available in the literature [22][23][24][25

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

• believed to occur during the work-up with methanol. Dinger and Mol also carried out studies supporting this theory [30]. In their report, they elucidated the degradation pathway of the first generation Grubbs catalyst (G-I) in the presence of primary alcohols and water (Scheme 4). The detrimental effect of

• 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

• metathesis (ADMET), ring-closing metathesis (RCM), ring-opening metathesis (ROM), and cross-metathesis (CM). Catalytic cycle for metathesis proposed by Chauvin. First aqueous ROMP reactions catalyzed by ruthenium(III) salts. Degradation pathway of first generation Grubbs catalyst (G-I) in methanol. Synthesis

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• -substituted vinylsilanes with Grubbs catalyst of first or second generation (A), the active methylene complex B and the corresponding (E)-1-phenyl-2-(silyl)ethene are formed. The methylene complex B in the presence of styrene undergoes metathetic conversion to benzylidene complex A and ethene. When dichloro

• -substituted vinylsilanes are used, the pathway shown in Scheme 1b is also possible. Metathesis of dichloro-substituted vinylsilanes with Grubbs catalyst A leads to styrene and (silyl)methylidene complex C. Formation of (silyl)methylidene complex C has not been confirmed by spectroscopic methods. The reaction

• of the postulated complex C with vinylsilane gives the corresponding (E)-1,2-bis(silyl)ethenes and the methylene complex B. The methylene complex B may react with vinylsilane to form ethene and regenerate complex C. In the presence of vinylsilanes containing alkyl substituents the Grubbs catalyst

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

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• metathesis to oxepines 11 smoothly in the presence of second-generation Grubbs’ catalyst A [54] within one hour at 90 °C, except for the 4-phenyl-substituted derivative 9b, which was recovered from the reaction mixture under these conditions. However, compound 9b was successfully cyclized to 11b using

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

• generation Grubbs catalyst (GrI) and M1 indenylidene catalyst (Ind). New complexes were formed by replacing one PCy3 phosphine ligand with the cationic NHC 1–3 (Scheme 1). We considered only the dissociative mechanism of initiation, in agreement with the numerous reports on the initiation of Grubbs catalyst

• experimental value. Clearly, DLPNO-CCSD(T) overestimates ΔG values for this series, though it gives very consistent results with the DFT method for other studied systems, described later. At this point we cannot provide any explanation of this discrepancy. Second generation Grubbs catalyst Second generation

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

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

• structure play a significant role in determining the metathesis reaction course. Experimental General experimental methods are similar as described in [49] Synthesis of triene 11. A solution of the silyl ether 7a (120 mg, 0.35 mmol) in degassed toluene (7 mL) with Grubbs’ catalyst G-II (30 mg, 0.035 mmol

• ; found, 539.2802. Synthesis of tetracycle 12b. A solution of the norbornene derivative 7b (70 mg, 0.18 mmol) in degassed toluene (6 mL) was heated with Grubbs’ catalyst G-I (15 mg, 0.018 mmol) under ethylene atmosphere at 65 °C for 12 h. After completion (TLC) of the metathesis reaction, dimethyl

• , 1249 cm−1; HRMS–ESI m/z: [M + Na]+ calcd for C31H46O7SiNa 581.2911; found, 581.2914. Synthesis of the tetracycle 20. The dienyne 18 (100 mg, 0.25 mmol) in degassed anhydrous toluene (7 mL) was treated with Grubbs’ catalyst G-II (22 mg, 0.025 mmol) at 65 °C for 5 h. On completion of the reaction (TLC

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• Grubbs' catalyst added (2 mol %). The sample was refluxed, and then filtered through silica gel. The filtrate was concentrated and treated with H2 (5 bar) and Wilkinson's catalyst (55 °C). The mixture was taken to dryness and the residue tediously chromatographed on a silica gel column. Numerous

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• the presence of Grubbs’ catalyst and thiol groups irradiated by UV light. Besides, the shuttling movement of the DB24C8 macrocyclic ring was confirmed by 1H NMR spectroscopy. Results and Discussion The structures of the two states of [2]rotaxane R1 are shown in Scheme 1. In the target structure [2