One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• alcohol 285. Oxidation with Dess–Martin periodinane of the alcohol 285 followed by ring-closing metatheses in the presence of 1 mol % of the second generation Grubbs catalyst (287) gave the 5H-benzo[7]annulene-5,6(7H)-dione monoketal 288 in nearly quantitative yield. The hydrolysis of 288 with excess p

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

• –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

• , 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

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

• . The latter could be constructed through ring-closing metathesis of the corresponding precursor, e.g., 4,4,5,5-tetrafluoroocta-1,7-diene 5, using a Grubbs' catalyst. The octa-1,7-diene 5 could be obtained through a nucleophilic addition of a vinylic Grignard reagent to the γ-keto ester 6. Lastly, the γ

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

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• second-generation Grubbs’ catalyst. The resulting chlorocyclohexene derivative 10 was oxidized to α-chloroketone 11, which was subsequently transformed into α-chlorooxime TBS ether 12 by standard oximation reaction. The required nitrosoalkene intermediate was generated from α-halo-O-silyloxime 12 upon

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• , EtOAc, rt, 6 h, 83%; (iii) LAH, THF, 0 °C to rt, 2 h, 81%; (iv) (COCl)2, DMSO, N-methylmorpholine, CH2Cl2, −78 °C to 0 °C; (v) MePh3PBr, n-BuLi, THF, 0 °C, 3 h, 72% over two steps; (vi) chromic acid, acetone, 2 h, 73%; (vii) Cs2CO3, CH3I, DMF, 2 h, 88%. Reagents and conditions: (i) Grubbs’ catalyst 12

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

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

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• conditions used in this study proved to be very robust and delivered the macrocyclic product in moderate yields. To begin our RCM endeavor, we performed the macrocyclization reaction on cycloadduct 3a in dichloromethane (10 mM) heating at 50 °C with 2 mol % second generation Grubbs catalyst. The reaction was

• on isolated yield obtained in the individual steps, we explored the feasibility of the RCM reaction without isolating the product at the couple phase. Compounds 4e–h were synthesized without purifying the respective cycloaddition products. The second generation Grubbs catalyst catalyzed RCM reaction

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

• -trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium reduced the isomerization, leading to an (E/Z)-mixture of 2. Finally, the (Z)-selective Grubbs catalyst 12 furnished the best results [29][30]. This catalyst yielded only the desired product (R)-2 with a (Z

• material. After copper-catalyzed opening of the epoxide with 6-heptenylmagnesium bromide obtained from 7-bromo-1-heptene (14) and Steglich esterification with 5-hexenoic acid (16), RCM using (Z)-selective Grubbs catalyst 12 was used to synthesize macrolide (R)-1 without any isomerization. Comparison of the

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• pyridine, stirring rt, 8 h; 2) 5-bromopentane, LiH, dry THF–DMSO, reflux, 4 h; 3) acetic anhydride, dry pyridine, MW, 50 °C, 1 h; 4) Grubbs’ catalyst, Ar, dry CH2Cl2, US, 34 °C; 5) KOH, 2 M, MeOH, H2O; US; 40 °C, 30 min; 6) AcCl 2% in MeOH; CH2Cl2, MW, reflux, 15 min. Insoluble reticulated CD polymer. CD

Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• be remarked that this Grubbs catalyst favored the polymerization under mild reaction conditions and tolerated very well the bulky POM cluster attached to the monomer. The obtained hybrid materials are promising candidates for the production of high-performance catalysts based on poly(polyoxometalate

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

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• various cross metathesis reactions, the phosphine-free Hoveyda type second generation Zhan catalyst-1B [30] was selected to conduct this transformation. A recent study by Fogg rationalized the superiority of the Hoveyda catalyst vs the Grubbs catalyst in cross metathesis with acrylates showing that the

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

• -heterocyclic ligand (NHC), depending on the first or second generation Grubbs catalyst. Here, DFT calculations unravel to which extent the bottom coordination of olefins with respect is favored over the side coordination through screening a wide range of catalysts, including first and second generation Grubbs

Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Mukesh E. Shirbhate

Beilstein J. Org. Chem. 2015, 11, 1514–1519, doi:10.3762/bjoc.11.165

• Vilsmeier–Haack reaction starting with the thiophene [33]. Later, diol 6 was oxidized with MnO2 [34] to deliver diketone 3. Our attempts to realize the RCM product 2 with dione 3 via a reaction with Grubbs’ catalyst failed to give the expected cyclized product. In most instances, we observed the degradation

• related to 3. Later, the bisindole derivative 5 was subjected to RCM in the presence of Grubbs’ 2nd generation catalyst to deliver the desired product 1 in good yield (Scheme 2). The sulfur atom present in the bisolefin 3 is more accessible for coordination with the Grubbs’ catalyst. Whereas in case 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

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• %) and 10b (56%). Compounds 10a and 10b were poised for RCM by virtue of the two alkenes present in them. RCM of each one, using the second generation Grubbs catalyst, provided E-configured macrolides 5 and 6 in 55 and 66% yield. Both compounds were isolated as crystalline solids after purification by

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

• 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

• olefin) were examined (Scheme 6). The mono-allyl vinylphosphonate 14a was treated with methyl acrylate, 10 mol % Grubbs catalyst and 10 mol % CuI in refluxing CH2Cl2. The unsaturated ester 16b [29] was formed in 78% yield (estimated from NMR). However, ester 16b is volatile and isolation by column

• separation of the crude product gave the unsaturated ester 16b in 86% isolated yield. It is proposed that the Grubbs catalyst first reacts with the terminal alkene (Scheme 11) of the allyl phosphonate ester 21a to give the metal alkylidene 33. The metal alkylidene then reacts with the vinylphosphonate in a

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

• glycodendrons 5 and 9 with terminal alkenes of different chain length (Scheme 3). Indeed, reaction of 5 and 1-decene using Grubbs’ catalyst (5%) led to the alkene 14 in 81% and the analogous reaction with 1-pentadecene and 10% Grubbs’ catalyst furnished 15 in 64% yield. Interestingly, in both cases, the trans

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

• initially tested for the cross metathesis of 2 and acrolein (Table 1). We started with the most common catalyst, the second generation Grubbs’ catalyst. In order to suppress undesired double bond isomerization reactions [51][52] we tried to avoid high reaction temperatures, which may cause catalyst

• for a metathesis based synthesis of protected L-amicetose and L-cinerulose. It undergoes a clean and high yielding cross metathesis reaction with acrolein, however, the most commonly used second generation Grubbs’ catalyst is not the ideal initiator for this particular transformation. Significantly

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• phosphinic acid using different alcohols in large excess (Scheme 1) [11][12]. Six phospholes 2a–f were prepared in yields up to 94%. Montchamp and coworkers have synthesized phospholes 4a,b by ring closing metathesis using 2 or 5 mol % of 2nd generation Grubbs’ catalyst (Scheme 2) [13][14]. Two compounds 4a

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

• ]. a) DDQ, CH2Cl2, rt, 30 min (85%); b) DMP, CH2Cl2, rt, 2 h; c) NaOCl, 2-methyl-2-butene, t-BuOH, phosphate buffer, rt, 16 h; d) TMS-CHN2, toluene/MeOH 2:3, rt, 40 min (58% over three steps); e) second generation Grubbs catalyst, crotonaldehyde, CH2Cl2, 40 °C, 120 min (88%); DDQ = 2,3-dichloro-5,6

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