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

• bromide, its allylated product 13 further cyclized into bis(1,2-oxaphosphepine 2-oxide) derivative tert-butyl 2,5,5a,6,9-pentahydro-[1,2]oxaphosphepino[2,3-b][1,2]oxaphosphepine-5a-carboxylate 11-oxide (14) in 97% yield under the same conditions (Scheme 2) [27]. The Grubbs 1st generation catalyst-promoted

• ][1,2]oxaphosphocine 2-oxides 18 in good to excellent yields in DCM at room temperature for 4–8 h in the presence of the Grubbs 1st generation catalyst. Two naphthylene-fused (19 and 20), pyrimidine-2,4(1H,3H)-dione-fused (21), and 2H-chromen-2-one-fused (22) 1,2-oxaphosphocine 2-oxides were also

• reaction with Grubbs 1st generation catalyst in DCM, affording 2-(4-methylphenyl)benzothiophene-fused 2-(benzyloxy)-1-oxa-2-phosphacycloundec-8-ene 2-oxide 35 in 70% yield with a ratio of 2:1 for the generated cis- and trans-double bonds. After Pd-catalyzed hydrogenolysis, it was converted into 2-(4

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

• 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

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• number of fluorine-containing alkenes (Figure 3). Compounds 7a and 7b as well as 7f–h were type I olefins, while acrylate esters 7c–e were type II olefins. Because 1st generation metathesis catalysts usually perform poorly in CM reactions with acrylates [31][32][36][39][41], only G-2, HG-2 and G-3 were

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

• -pyrans. Among the catalysts tested, Grubbs 1st generation precatalyst in the presence of ethene (Mori conditions) gave superior results compared to the more stable Grubbs or Hoveyda–Grubbs 2nd generation precatalysts. This is probably caused by a suppression of the subsequent side-reactions of the enyne

• intermediate to undergo subsequent metathesis reactions leading to catalyst deactivation [23]. In both cases, the effect of ethene was especially productive for the Grubbs 1st generation precatalyst and is typically applied for terminal alkynes or alkynes with little steric hindrance of the triple bond. In

• triple bonds, tolerating well various alkyl or ester groups. Among the catalysts used, the Grubbs 1st generation catalyst under Mori conditions worked best, while the Grubbs 2nd and Hoveyda–Grubbs 2nd generation precatalysts gave lower yields. For the 2nd generation precatalysts, Mori conditions could

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• synthesis of the dihydro-3-pyrone 58. Kitahara’s 1st-generation synthesis of the C-1–C-6 fragment of FR901464 (1). Kitahara 1st-generation synthesis of the C-1–C-6 fragment of FR901464 (1). Nimura/Arisawa synthesis of the C-1-phenyl segment. Ghosh synthesis of the C-1–C-6 fragment of FR901464 (1) from (R

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

• allyl ether (2R,1'R,1''R)-135 which in the presence of Grubbs 1st generation catalyst produced (2R,1'R,1''R)-136. Transformation of the aziridine portion of 136 into an amino acid fragment of norfuranomycin (2S,2'R)-133 was accomplished starting from the hydrolytic opening of the aziridine ring and was

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

• Gibbs free energies all system apart from 1st generation Grubbs and indenylidene-like complexes, for which we used pure M06. Results for all systems and both M06 and M06-D3 methods are listed in Supporting Information File 1. Dimerization The tendency of selected NHC to dimerize is a well-known and

• higher stabilities of dimers on solution (see Supporting Information File 1). First generation Grubbs and M1 indenylidene catalyst In the next step of the study we performed a computational investigation of possible pathways of the initiation of cationic ruthenium catalyst based on the commonly used 1st

• 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

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• modification of the first coordination sphere by adding an N-heterocyclic carbene (NHC) ligand and a chelating styrene to the so-called Grubbs 1st generation catalyst, the relatively air- and moisture-stable Grubbs–Hoveyda type (GH-type) catalysts were obtained [7]. These catalysts do not only show stability

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

• describe the results of metathesis of norbornene derivatives 2 with alkynyl side-chains. Results and Discussion Initially Grubbs’ 1st generation catalyst (G-I) was used for metathesis of norbornene derivatives 2. In case G-I failed to accomplish metathesis in the desired direction, 2nd generation catalyst

• compound 7a in toluene under ethylene atmosphere was heated at 65 °C with Grubbs 1st generation catalyst (G-I). Compound 7a was found to be inert even after a prolonged reaction time. However, with G-II as the catalyst the metathesis went smoothly. Without isolation, the metathesis product was treated in

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

• diiodobenzene 11 using allylboronate ester 12 via a SM-type allylation sequence [32]. Next, compound 13 was exposed to Grubbs 1st generation (G-I) catalyst 1 to effect the ring-closure to produce tetrahydronaphthalene derivative 14 (92%). Subsequently, aromatization of compound 14 was accomplished with 2,3

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• performed using Grubbs’ 1st generation catalyst (3–20 mol %) was unsuccessful. Treatment of 10 with ethyl vinyl ketone using Grubbs’ 2nd generation catalyst (3 mol %) in the presence of CH2Cl2 furnished (E)-enone 11 in 77% yield as shown in Scheme 4. In the 1H NMR spectrum, 11 showed a signal at 6.13 ppm as

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• , the PMB-protected epoxide 121 was converted to diene 122. The dihydropyran ring of 123 was constructed by RCM of 122 catalyzed by a Grubbs 1st generation catalyst. The isomerization of the double bond in 123 by treatment with a Wilkinson catalyst under basic conditions afforded glycal 124 (Scheme 16

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• -closing metathesis [23][24][25] of 5a under the influence of less than 10 mol % of a Grubbs 1st generation catalyst did not proceed to completion, resulting in recovery of the starting material along with the desired adduct 4a. Increasing the reaction temperature did not lead to satisfactory results

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• Cs2CO3 for 3 hours finally afforded phenytoin in an excellent 84% isolated yield (Scheme 16c). The introduction of a sulfonyl group on the urea framework has been found to be the crucial structural modification in the development of the 1st generation antidiabetic drugs such as tolbutamide and

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• syntheses of the mycolactone core and of Blanchard’s synthesis of its 8-desmethyl derivative. A common element between Kishi’s 1st generation approach and Negishi’s and Aggarwal’s strategies consists in the assembly of the entire linear C1–C20 fragment prior to macrocyclization. For most other syntheses

• homologation methodology; the required fragments were also obtained by the sequential application of this methodology. Of note, Burkart’s 1st generation approach aiming to assemble the cyclized C1–C14 fragment with the C15–C20 extension was unsuccessful, since the keto group located at C14 failed to undergo

• time, leading to three distinct generations of syntheses. The 1st generation synthesis [39] was developed in 2001 with the intention to confirm the mycolactone core structure, including the unambiguous assignment of its relative and absolute stereochemistry. In their 2nd generation approach [122

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• yielding synthesis (Figure 1). Results and Discussion 1st Generation NeoPHOX ligands A potential very short route to NeoPHOX ligands starting from commercially available 3-chloropivaloyl chloride (3) is shown in Scheme 1. Although nucleophilic substitutions at the neopentyl carbon atoms are known to be

• configuration at the hydroxy-substituted carbon atom. Double addition of methylmagnesium chloride and subsequent introduction of the diphenylphosphine unit proceeded well in 68% yield following the procedures worked out for the 1st generation NeoPHOX ligands. Alternative strategies involving Grignard addition

• anions were omitted for clarity. Retrosynthetic analysis for NeoPHOX ligands. Synthesis of 1st generation NeoPHOX Ir-complexes [19]. Synthesis of a C(5)-disubstituted NeoPHOX-Ir complex. Revisited synthetic strategy for the preparation of a threonine-based NeoPHOX ligand. Undesired β-lactam formation

The role of alkyl substituents in deazaadenine-based diarylethene photoswitches

• Christopher Sarter,
• Michael Heimes and
• Andres Jäschke

Beilstein J. Org. Chem. 2016, 12, 1103–1110, doi:10.3762/bjoc.12.106

• important direction for the design of new efficient photoswitches for application in bionanotechnology and synthetic biology. Diarylethene photoswitches. A: classical design and photoisomerization reaction [27]. B: purine-based photoswitches (1st generation) [43][44], C: pyrimidine-based photoswitches (2nd

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• catalyst The new catalyst, 9, was obtained from imidazolinium salt 14 by deprotonation with potassium tert-amylate followed by the tricyclohexylphosphine ligand exchange in Hoveyda–Grubbs 1st generation catalyst to give the target catalyst 9, which was purified on silica gel. The complex was stable in

• were recorded on a Nicolet series II Magna-IR 550 FTIR spectrometer. Flash chromatography (FC) was performed on silica gel 230–400 mesh. Catalysts: 1, 2, 3 and the Hoveyda–Grubbs 1st generation complex were purchased from Apeiron Synthesis. 2,2,5,7,8-Pentamethylchromane (10) was prepared from 2,3,5

• stirred for 20 min at rt. Then a solution of Hoveyda–Grubbs 1st generation catalyst (96 mg, 0.16 mmol) in toluene (3 mL) was added and the reaction was carried out at 65 °C for 2 h. The reaction mixture was purified by column chromatography (hexane/ethyl acetate 10:1) to give a green solid (86 mg, 68

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

• Jyotiprasad Mukherjee,
• Suman Sil and
• Shital Kumar Chattopadhyay

Beilstein J. Org. Chem. 2015, 11, 2487–2492, doi:10.3762/bjoc.11.270

• (Scheme 2) with ethyl vinyl ketone in the presence of Grubbs’ 1st generation catalyst (G-I) proved to be unsuccessful in our hands under a range of conditions. However, changing to the 2nd-generation catalyst [(1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene

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

• PCy3 > P(iPr)3 >> PPh3. Reactions had to be performed in degassed and distilled solvents under N2 atmosphere to obtain maximum yields. Grubbs’ 1st generation catalyst To overcome the aforementioned difficulties, Grubbs and co-workers synthesized, what has become known as the Grubbs’ 1st generation

• reactions of tri- and tetrasubstituted olefins [42][46], cross-metathesis (CM) to afford trisubstituted olefins [44] and CM and RCM reactions of electron-withdrawing substituted olefins [45]. In comparison to the 1st generation, they show a generally higher stability towards thermal degradation [41][42][43

• their ease of synthesis [77][79][80]. Complex 82 is air-stable in the solid state; however, it does not show activity in metathesis-type reactions. On the other hand, its PCy3 counterpart 83 is as active as the Grubbs’ 1st generation catalyst [73][80][81]. The NHC-bearing complexes (74, 84–86) showed

Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• -defined, hydrophilic Ru–alkylidene catalysts in combination with a hydrophobic monomer in emulsion. The first emulsion ROMP was reported in the early 2000’s when Claverie et al. used 1st generation Grubbs-type catalysts [24] 1 and 2 (Figure 1, approx. 400 ppm catalyst loading) to effectively polymerize

• norbornene (NBE) at 80 °C in microemulsion (91% conversion) [54]. The same conditions failed to polymerize significant amounts of the far less reactive monomers cyclooctene (COE) or cyclooctadiene (COD) with yields below 10%. Later, Heroguez et al. synthesized the 1st generation Grubbs-type macroinitiator 3

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• the ring-closing metathesis with umbelliferone precursor 8 were determined with different catalysts 1–4 (Figure 2). It is known that acryloyl ester substrates are poor substrates which typically give low yields with 1st generation precatalysts [27]. As the reactions were performed in air and with very

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

• -chloroform mediated by the 1st generation Grubbs’ catalyst Cl2(PCy3)2Ru=CHPh is studied by monitoring the kinetics of carbene transformation and evolution of the dyad composition of polymer chains with in situ 1H and ex situ 13C NMR spectroscopy. The results are interpreted in terms of a simple kinetic two

• 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

• noteworthy that the reaction is readily mediated by the 1st generation Grubbs’ catalyst Cl2(PCy3)2Ru=CHPh (Gr-1), which is not suitable for metathesis ring-opening copolymerization of NB and COE. Our approach makes it possible to synthesize statistical multiblock NB-COE copolymers containing up to 50% of

A comprehensive study of olefin metathesis catalyzed by Ru-based catalysts

• Albert Poater and
• Luigi Cavallo

Beilstein J. Org. Chem. 2015, 11, 1767–1780, doi:10.3762/bjoc.11.192

• favored only for some systems. Specifically, for the 1st generation system 1, for symmetric NHC systems with small N-substituents, such as 3, for all the pseudo-halide systems, and for system 13, with a C1-symmetric NHC ligand. Differently, for non pseudo-halide NHC systems with N-substituents bulkier

• , whereas in 7 the trans path is favored. Furthermore, the energy gain associated with metallacycle formation is quite higher in the 2nd generation catalyst rather than for the 1st generation catalyst. Moving to the same catalysts with the bigger substrate, systems 14 and 16, metallacycle formation is an

Design and synthesis of propellane derivatives and oxa-bowls via ring-rearrangement metathesis as a key step

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2015, 11, 1727–1731, doi:10.3762/bjoc.11.188

• with allyl bromide in the presence of NaH delivered the aromatized compound 2a in 42% yield. Then, the tricyclic compound 2a was subjected to RRM with Grubbs 1st generation (G-I) catalyst in the presence of ethylene to furnish the tetracyclic compound 1a in 75% yield (Scheme 1). The structures of