Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• –Smith cyclopropanation; Hyptis brevipes Poit; ring-closing metathesis; Introduction Hyptis brevipes Poit. is an invasive plant species belonging to the mint family Lamiaceae [1][2][3][4]. This plant has been reported to originate from tropical America but is now distributed broadly in other tropical

• followed by esterification with 3-butenoic acid (37) under Steglich conditions (Scheme 3). The resulting product 38 was isolated in 86% yield. A subsequent ring-closing metathesis reaction and DBU-assisted double bond migration then furnished the anticipated structure 39. The PMB functionality was removed

• acid (17) (Scheme 4). The β-hydroxy moiety in 44 can be installed via Sharpless dihydroxylation of the silyl enol ether derived from ketone 45. The 5,6-dihydro-α-pyrone group in ketone 45 is envisaged from protected diol 46 by the sequence of Mitsunobu esterification, ring-closing metathesis, and base

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• with a reaction yield ranging from 66% to 91% (Scheme 4). Finally, for some of the dyes, a metathesis reaction was carried out with sodium tetraphenylborate. Indeed, all dyes were obtained as iodine salts so that a counterion exchange could be carried out. Using this strategy, four “soft” salts could

• exposure to a laser diode at 785 nm (0.9 W/cm2), thickness = 1.4 mm. The irradiation starts at t = 10s. B) FTIR spectra before and after irradiation. Investigated NIR dyes. Other used chemicals. Synthetic routes to compounds Ca, Cb, and CNa. Synthetic routes to CI1, CI3, CI4, and CI6–CI9. The metathesis

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

• Abstract This work presents an examination of the selective functionalization of norbornadiene through nitrile oxide 1,3-dipolar cycloaddition/ring-opening metathesis (ROM)/cross-metathesis (CM) protocols. Functionalization of commercially available norbornadiene provided novel bicyclic scaffolds with

• the CM transformations with the goal of exploring substrate and steric effects, catalyst influence and chemodifferentiation of the olefin bonds furnishing the corresponding functionalized, fluorine-containing isoxazoline derivatives. Keywords: functionalization; metathesis; nitrile oxide

• ; organofluorine chemistry; selectivity; Introduction Olefin metathesis is considered to be a powerful synthetic tool for the creation of olefin bonds [1]. Several types of metathesis reactions, such as ring-opening metathesis (ROM), cross-metathesis (CM), ring-closing metathesis (RCM) or ring-opening/cross

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• sequential modifications [30], photocyclization of divinylterphenyl derivatives [31], tandem radical cyclization of (Z,Z)-1,4-bis(2-iodostyryl)benzene derivatives [32], and ring-closing olefin metathesis of tetravinylterphenyls [33] as the best-known synthetic routes. Herein, we have classified the synthetic

• published in 2018, de Koning and co-workers reported a new methodology to synthesize the benzo[a]anthracene skeleton of angucycline derivatives 146 by using a multistep strategy based on Suzuki–Miyaura, isomerization, and ring-closing metathesis reactions (Scheme 33) [67]. The commercially available 2

• metathesis strategy to synthesize benz[a]anthracenes. Green synthesis of oxa-aza-benzo[a]anthracene and oxa-aza-phenanthrene derivatives. Triple benzannulation of substituted naphtalene via a 1,3,6-naphthotriyne synthetic equivalent. Zinc iodide-catalyzed Diels–Alder reactions with 1,3-dienes and aroyl

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• , several products were submitted to a subsequent metathesis mediated by Grubbs-II catalyst and a further palladium-catalyzed C=C reduction and DG-removal process, from which the desired macrocyclic peptides were obtained in good to excellent yields (Scheme 35C). Recently, again Ackermann and co-workers

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

• -closing metathesis (RCM), Clauson–Kaas and Ullmann-type coupling reactions as key steps. Moreover, we have also assembled some other interesting heterocyclic systems possessing oxazole, imidazole, benzimidazole, and benzoxazole in the framework of truxene. Additionally, the preliminary photophysical

• properties (absorption and emission) for these versatile systems has been revealed. Keywords: Clauson–Kaas reaction; heterocycles; ring-closing metathesis; truxene; Ullmann-type coupling; Van Leusen reaction; Introduction The two-dimensional phenylene-based π-conjugated star-shaped architectures has

• metathesis, Ullmann-type coupling, Clauson–Kaas, and Van Leusen reactions as crucial transformations. Synthetic Strategy Basically, our endeavor toward the synthesis of truxene-based systems has been rooted in the development of new synthetic methodologies to assemble diverse polycyclic as well as

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

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• number of classical methodologies have been used for their synthesis, in which the key step is the generation of the six-membered ring, including the aldol reaction, the reductive amination, Mannich reaction, ring closing metathesis, Diels–Alder reaction with imines as dienophiles, aza-Prins cyclization

• products were obtained after four additional steps: cross-metathesis of allylated compounds 120 with methyl vinyl ketone, reduction of conjugated C=C double bond, removal of the sulfinyl group under acidic conditions, and final stereoselective reduction of the imine formed by intramolecular cyclization

• subsequent steps, including ring-closing metathesis [133], (−)-cermizine B (171) and (+)-serratezomine E (172) were obtained 57% and 72% yield, respectively (Scheme 43) [134][135]. Cyclizations involving a position in the attacking nucleophile Isosolenopsin (177) and solenopsin (178) are two isomeric

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• metathesis (RCM) [16], halo etherification [17], reductive etherification [18][19], and metal-mediated cyclization [20][21], etc. are the most frequent strategies utilized for THP ring construction (Scheme 1). Amongst all, the Prins reaction has proven as a powerful technique in the stereoselective synthesis

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• cosmetics [147]. The catalyst could be recycled, however, with reduced performance due to Pt nanoparticle oxidation. 3.1.2 Polybutadiene (PBD): Partial depolymerisation of 1,4-PBD (cis, trans, Mw 1800–500000 g⋅mol−1) was achieved by an unconventional tandem ring-opening–ring-closing metathesis route

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• additional unit of hydrogen sulfide can lead to the trisulfides 3 and 32 (Scheme 4C), while higher polysulfides such as 34 can arise through a metathesis reaction of two trisulfides (Scheme 4D). Also traces of methyl 3-(allylsulfanyl)propanoate (24), methyl 3-(methyldisulfanyl)propanoate (25), and methyl 3

• synthesized by a method reported previously for the related compound 25 [40], through dimerization of methyl 3-mercaptopropanoate (39) to dimethyl 3,3’-disulfanediyldipropanoate (40), followed by the BF3·OEt2-mediated metathesis with 2 (Scheme 5A). The synthetic compound 26 was identical by mass spectrum and

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• the activity is controlled by the ring C. Keywords: chiral resolution; configurational analysis; glutamate; metathesis; neuroactivity; Introduction The ionotropic glutamate receptor (iGluR) mediates the majority of the excitatory neurotransmission in the mammalian central nervous system (CNS) and

• ], the heterotricyclic framework was constructed over a five-step sequence including the domino metathesis reaction as a key step to give (rac)-7. The subsequent three steps from (rac)-7 (esterification with CH2N2, PMB removal, and ester hydrolysis) had been proven to be promising for the preparation of

• ). Enantiospecific synthesis of TKM-38 For the enantiospecific synthesis of TKM-38, which uniquely bears an eight-membered azacycle as the ring C, we explored 1) the amino-protecting group and 2) the conditions for the cyclization of the medium-sized ring by ring-closing metathesis (RCM). Finally, the established

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• reactions (Scheme 1a). Diels–Alder (Scheme 1b) [15] and radical reactions (Scheme 1c) [16] directed toward helicene synthesis require high temperature conditions even for low to moderate yields. Olefin metathesis (Scheme 1d) [17] and alkyne trimerization (Scheme 1e) [18][19] require the use of expensive

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• with a cleavage of the distal C–C bond. The reaction proceeded regioselectively and in high yields. There was no difference observed between cis and trans-isomers in terms of the reactivity and yields. The resultant dienes 129 were used in ring-closing metathesis reactions to furnish gem

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• formal synthesis of inthomycin C ((−)-3). In 2018, Donohoe et al. demonstrated a tin-free, short and efficient total synthesis of inthomycin C ((−)-3) by comprising the three key steps of C−C bond-forming reactions: i) a vinylogous Mukaiyama aldol reaction, ii) an olefin cross-metathesis reaction, and

• -metathesis reaction of 121 with alkene fragment (rac)-118 in the presence of Grubbs II (G-II) catalyst under optimized conditions produced (rac)-122 in 57% yield. After exhaustive experimentation, demethoxylation of (rac)-122 was achieved to produce (E,E,E)-aldehyde 123 predominantly in an 8:1 mixture of

• ((−)-3). Synthesis of the cross-metathesis precursors (rac)-118 and 121. Donohoe’s total synthesis of inthomycin C ((−)-3). Synthesis of dienylboronic ester (E,E)-128. Synthesis of the alkenyl iodides (Z)- and (E)-130. Burton’s total synthesis of inthomycin B ((+)-2). Burton’s total synthesis of

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

• chemical ecology of Adalia bipunctata and the recent methodologies to obtain adaline (1), euphococcinine (2), and N-methyleuphococcinine (3). Keywords: 9-azabicyclo[3.3.1]nonane; Coccinelid beetles; dipolar cycloaddition; homotropane; ring-closing metathesis; Introduction Coccinellid beetles contain a

• , activated by lithium ion in a tricyclic N,O-acetal (−)-46, and an olefin metathesis (RCM) of a dialkenylpiperidine (−)-50 for the construction of an azabicyclononane system [48]. The synthetic sequence described by the authors is shown in Scheme 6. The lactam present in 43 was opened by treatment with

• (−)-48, in 88% yield, as a single diastereoisomer. Then, (−)-48 was treated with trimethyl orthoformate to provide formamide (−)-49, being converted to cis-2,6-dialkenylformamide (−)-50 by treatment with the Lindlar catalyst. (−)-50 underwent a ring-closing metathesis efficiently in the presence of the

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• 60% yield (74% yield, brsm). A two-step synthesis from 127 produced diene 128, which was subjected to ring-closing metathesis and subsequent Dess–Martin oxidation to give 129 in 63% yield over two steps. Tetracycle 130, which was prepared from 129 in one step, was converted to lycojaponicumin C (18

• and AIBN to a refluxing solution of cyclopropane 155 afforded 156 in 38% yield. It was subjected to cleavage of the Boc group followed by N-allylation to give 157 in 73% yield over two steps. A ring-closing metathesis of freshly prepared 157 was effected by the second generation Hoveyda–Grubbs (HG II

• of aldehyde 163 and isoprene (164) with Ni(acac)2 and diethylzinc [78] and then Dess–Martin oxidation gave a diene (not shown, 94% yield over two steps), which was subjected to ring-closing metathesis to give enone 165 in 85% yield. Isomerization of the freshly prepared 165 to more stable α,β

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• , ring-closing, metathesis, cycloadditions, radical reactions and microwave-assisted reactions [38][39][40]. In this work, we attempt to develop a greener, simpler, more efficient and recyclable system to synthesize arylpyridine derivatives. Initially, the reaction of acetophenone (5a) and 1,3

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

• metathesis product with ethene. On the other hand, the 2nd generation precatalysts gave better yields in the absence of ethene. The metathesis products, containing both a triple bond and a conjugated system, can be successfully orthogonally modified. For example, the metathesis product of 5-(allyloxy)nona

• -2,7-diyne reacted chemo- and stereoselectively in a Diels–Alder reaction with N-phenylmaleimide affording the tricyclic products as a mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to the

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• [13][17][18][19][20]. The first-generation TLC approach for the synthesis of molecular knots involved a single knot precursor compound that had two macrocycles and two long tails [13][21]. Solvophobic effects [22][23] were used to promote the tail threading step, ring-closing olefin metathesis (RCM

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• catalyst 15 to yield the trimerized products 12 (syn) and 13 (anti) in respectable yields (Scheme 2). The alkene-bridge exchange of 12 (syn) was accomplished by tandem ring-opening and ring-closing metathesis (ROM–RCM) in the presence of Grubbs’ first generation (G-I) catalyst to generate a C3-symmetric

• hexahydrosumanene 17 which on subsequent aromatization using DDQ furnished the desired molecule sumanene (2) in good yield. To their surprise, tandem metathesis for achieving compound 17 from 13 (anti) was fruitless may be because of the endothermic reaction by 37.4 kcal/mol as compared to the exothermic (51.4 kcal

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• metathesis using Grubbs’ 2nd generation catalyst (G-II, Scheme 3) [13]. Replacing the N-Boc protecting group with an N-tosyl group and allylic oxidation gave 30. The introduction of the allyl group at C-11 made use of the Kishi protocol [22] of the allyl-Grignard addition, followed by an ionic reduction. The

• yield and high enantioselectivity (Scheme 7) [15][16]. The Achmatowicz oxidation and ionic reduction generated the enone 58, which is regioisomeric with 53. The 1,4-addition of lithium dimethylcopper gave the desired cis-55 with high a diastereoselectivity (25:1). The cross-metathesis of 55 with 3

• generation of the mixed acetal 113 (Scheme 18) [33]. A ring-closing metathesis gave an inseparable mixture of the dihydropyranyl ethers 114a and 14b, which could be equilibrated under acidic conditions (114b/114a > 20:1). A standard functional group manipulation afforded the vinyldihydropyran-2-one (−)-115

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

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• synthetic strategies. Such examples in recent years include olefin metathesis [1] as well as C–C and C–N coupling reactions [2], among the most obvious examples. While these reactions undoubtedly had very significant impacts on the development of much cleaner and efficient chemical synthesis strategies, the

• , explaining the experimental observations for C–H activation reactions, depending on the nature of a ligand (Ln) and transition metal (M) in the catalytically active species (LnM). These mechanisms include four elementary steps: oxidative addition, σ-bond metathesis, electrophilic substitution and 1,2

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