Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• was subjected to a third round of chromatography (toluene/ethyl acetate 3:2 → toluene/ethyl acetate/acetone 2:2:1) to afford the title compound as an oil (661 mg, 47%). Rf 0.35 (dichloromethane/methanol 9:1); 1H NMR (400 MHz, CD3OD) δ 1.02 (d, J = 6.5 Hz, 3H), 1.03 (d, J = 6.5 Hz, 3H), 1.59 (s, 3H

• of water with toluene (2 × 50 mL). The residue was purified by column chromatography (toluene/ethyl acetate/acetone 3:2:0–12:8:5) to afford the title compound as a yellow amorphous solid (345 mg, 56% corrected for the presence of ≈10 wt % toluene). The data are consistent with literature values [22

• . The residue was purified by column chromatography (toluene/ethyl acetate/acetone 3:2:0–0:1:1) to afford the title compound as a yellow glass (34.7 mg, 37%). The data are consistent with literature values [22]. Rf 0.40 (acetone/ethyl acetate/toluene 2:1:1); mp 49 °C [lit. mp not given]; IR νmax 3234br

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• of the experimental EPR spectra. It is noteworthy that semiquinone derivatives of 6b and 6d show resolved hyperfine splittings due to the coupling of unpaired electrons with the magnetic nuclei of 14N (quintet 1:2:3:2:1) and protons of methyl groups (septet 1:6:15:20:15:6:1), respectively. o

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• -purine-2,6-diyl)bis(1H-1,2,3-triazole-4-carboxylate) (6a, 0.20 g, 0.43 mmol, 1.0 equiv) was dissolved in P(OEt)3 (2 mL) and stirred for 3 hours at 160 °C. Then, the solution was cooled to room temperature, hexane (10 mL) was added, and the mixture was left in the freezer (−20 °C) for 10 h. The brown

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• obtained for the 3-(2-(dimethylamino)ethyl)aniline analogue 24j was due to the fact the 2-Cl-Py did not transform to the OAt ether in situ and the subsequent hydrolysis step was very sluggish. We postulate that the presence of the more basic N,N,-dimethylaminoethyl side chain (pKa ≈11) must prevent

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

• , stereo-congested, five-membered carbocycles containing all-carbon quaternary center(s) is, at present, a distinct challenge in modern synthetic chemistry, which can be accessed through the all-carbon [3 + 2] cycloaddition. More importantly, the all-carbon [3 + 2] cycloaddition can forge vicinal all

• -carbon quaternary centers in a single step and has been demonstrated in the synthesis of complex natural products. In this review, we present the development of all-carbon [3 + 2] cycloadditions and illustrate their application in natural product synthesis reported in the last decade covering 2011–2020

• (inclusive). Keywords: all-carbon; cyclization; [3 + 2] cycloaddition; natural product synthesis; stereocenters; Introduction The highly-substituted, stereo-congested, five-membered carbocycle containing contiguous stereocenters is one of the most common structural features in many structurally complicated

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• form can be explained by steric hindrance between the phenyl and the arylsulfonyl groups. Because of the observed evolution of nitrogen and sulfur in every reaction of heterocyclic thioamides and sulfonyl azides it is logic to propose the formation of a thiatriazole ring via [3 + 2] cycloaddition of

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• to the formation of two regioisomers, but interestingly, the ratio of the 7-CF2H- and 9-CF2H-isomers varied broadly from 1:2 [22] to 3:2, depending on the reaction conditions and the source of difluorocarbene [11]. Mechanism, regiochemistry, and rotation barriers of the CH(CF3)2 group The mechanism

• NMR data are given in Table 1 and Table 3. Reaction of 4-azabenzimidazole (3) and 1 A mixture of 1.2 g (0.01 mol) of 4-azabenzimidazole (3), 2 g (0.06 mol) of 1, and 15 mL of DMSO was agitated at ambient temperature for 24 h. The precipitated sulfur was filtered, washed with hexane, and dried on a

A heterobimetallic tetrahedron from a linear platinum(II)-bis(acetylide) metalloligand

• Matthias Hardy,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2020, 16, 2701–2708, doi:10.3762/bjoc.16.220

• , CD3CN, 298 K) δ [ppm] 4.66–4.47 (m); 19F NMR (470 MHz, CD3CN, 298 K) δ [ppm] −79.4 (CF3SO3−); DOSY (500 MHz, CD3CN, 298 K, τ = 150 ms): D = 3.33∙10−10 m2/s, dh = 33 Å, rh = 1.65 nm; ESI(+)-MS (CH3CN, M = {C320H432Fe4N24P12Pt6}8+) m/z: 1720.141 [M + 4OTf]4+, 1542.718 [Fe(C52H72N4P2Pt)3]2+, 1433.608 [Fe2

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• -Michael-type cycloadducts [28]. Very recently, a catalytic enantioselective (3 + 2) cycloaddition of diazabicyclohexanes with chalcones was carried out [30]. 1,5-Diazabicyclo[3.1.0]hexanes have been employed as precursors for 1,3-dipoles not only in (3 + 2) but also in (3 + 3) cycloadditions. It was shown

• investigated using only convection heating. The aim of the current work is to investigate the regio- and diastereoselectivity of the microwave-assisted (3 + 2) cycloaddition of 6-aryldiazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones. Results and Discussion Herein, we report the 1,3-dipolar

• cycloaddition reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes 1a–d (DABCH) with 1,3-diarylpropenones 2a–l at 110 °С under microwave irradiation using a microwave oven Discover SP in a 10 mL glass reactor. It was found that under these conditions the (3 + 2) cycloaddition products – perhydropyrazolopyrazoles

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• ). This allowed for a larger reactor volume with the same illumination. The throughput was increased by using a larger volumetric flow rate. Several [3 + 2] photocycloadditions were performed. While scaling up, the concentration of the reactants, the diameter of the tubes, and the number of the reactors

Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

• Tatsuhiro Uchikura,
• Nanami Kamiyama,
• Taisuke Ishikawa and
• Takahiko Akiyama

Beilstein J. Org. Chem. 2020, 16, 2442–2447, doi:10.3762/bjoc.16.198

• ) gave product 3h in only a modest yield (30%). Heteroaryl iodides were also suitable substrates (Figure 3). 2-Iodopyridine (5a) gave the expected trifluoromethylation product 6a in 80% yield. 2-Iodoquinoline (5b) and 1-iodoisoquinoline (5c) were also suitable substrates to furnish desired products 6b

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• and enantioselectivities (12 examples, up to 97:3 er). Yoon et al. later expanded the scope of this reaction to cyclopropyl ketones 275 for the synthesis of formal [3 + 2] cycloaddition products 276 in excellent yields and enantioselectivities (21 examples, up to >99:1 er), this time using a

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• good yield. Dehydrogenation of 7 with chloranil then provided 9-(dimethylamino)-9-(trifluoromethyl)fluorene 8. In an analogous reaction sequence, 11H-benzo[a]fluorene derivative 9 was obtained from 3-(2-naphthyl)propyn-1-iminium salt 1b and 2,3-dimethylbutadiene (Scheme 2) in a one-pot three-step

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• developing a robust strategy in regards to the potential application of our route to the production of other lipid A analogs. Results and Discussion The acyl chain (R)-3-(2-naphthylmethoxy)tetradecanoic acid 7 was prepared via an enantioselective route as previously reported (Scheme 1) [16]. Lauroyl chloride

• with LiOH gave (R)-3-(2-naphthylmethoxy)tetradecanoic acid (7) in 78% yield over two steps. The glucosamine building block 14 was synthesized using the procedures described in previous literature [20] (Scheme 2). The protection of the free amine of glucosamine with a 2,2,2-trichloroethoxycarbonyl (Troc

• with (R)-3-(2-naphthylmethoxy)tetradecanoic acid (7) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) as the activation reagents [14] to give the key/common building block 15 in good yield (Scheme 2). Glycosyl acceptor 18 and donor 20 were thus conveniently

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• Earth Sciences, St. Petersburg State University, Universitetskaya emb. 7/9, St. Petersburg, 199034 Russia 10.3762/bjoc.16.161 Abstract A series of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines was synthesized for the first time by the reactions of chloroethynylphosphonates with unsubstituted and 5

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• over MgSO4, and the volatile components were removed under reduced pressure. The yellowish residue (crude product) was purified by flash chromatography over silica gel, with a mixture of n-hexane/ethyl acetate 3:2, v/v as eluent. The fractions containing the product (Rf = 0.22 in n-hexane/ethyl acetate

• 3:2, v/v) were combined, and the solvents were removed under reduced pressure on a rotary evaporator to give Cit-BZP-yne (154 mg, 0.38 mmol, 67%) as white solid. 1H NMR (300 MHz, CDCl3, δ):7.85–7.72 (m, 4H), 7.09–6.99 (m, 2H), 7.02–6.91 (m, 2H), 5.61–5.49 (m, 1H), 4.77 (d, J = 2.4 Hz, 2H), 4.47 (s

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• reported under these conditions, special care should be taken for large-scale preparations. p-Methoxyphenyl (2-O-acetyl-α-ʟ-rhamnopyranosyl)-(1→3)-(α-ʟ-rhamnopyranosyl)-(1→3)-(α-ʟ-rhamnopyranosyl)-(1→3)-2-acetamido-6-O-acetyl-2-deoxy-β-ᴅ-glucopyranoside (1): To a solution of compound 7 (300 mg, 0.21 mmol

• -20 column using CH3OH/H2O 6:1 as eluent to give pure compound 1 (90 mg, 50%). p-Methoxyphenyl (2,4-di-O-benzyl-α-ʟ-rhamnopyranosyl)-(1→3)-2-azido-4,6-O-benzylidene-2-deoxy-β-ᴅ-glucopyranoside (5): To a solution of compound 2 (600 mg, 1.5 mmol) and compound 3 (800 mg, 1.57 mmol) in anhydrous CH2Cl2

• SiO2 using hexane/EtOAc 3:1 as eluent to give pure compound 5 (806 mg, 73%). p-Methoxyphenyl (2,4-di-O-benzyl-α-ʟ-rhamnopyranosyl)-(1→3)-(2,4-di-O-benzyl-α-ʟ-rhamnopyranosyl)-(1→3)-2-azido-4,6-O-benzylidene-2-deoxy-β-ᴅ-glucopyranoside (6): To a solution of compound 5 (700 mg, 0.96 mmol) and compound 3

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• immobilisation is common with transition metal complexes as they are often inherently cationic species. Amara and co-workers recently showed that [Ru(bpy)3]2+ could be immobilised on silica particles with a dramatic increase in the efficiency of the photooxidation of terpenes [137]. Polymer networks containing

• bipyridyl units have been designed to immobilise transition metal complexes through coordinate bonding for the oxidative coupling of amines [138]. [Ru(bpy)3]2+ units were synthesised with ethynyl groups para-substituted to the nitrogen heteroatom on four of the six pyridine rings. The ethynyl groups were

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• of a [3 + 2] cycloaddition reactions under UV irradiation with azobis(isobutyronitrile) (AIBN) as the free radical initiator and phenyl disulfide as the catalyst, in which the three-membered rings containing double bonds and substituted olefins were transformed into five-membered-ring structures with

• used similar disulfide-catalyzed [3 + 2] cycloaddition reactions for the synthesis of polycyclic frameworks. The irradiation of vinylcyclopropanes with alkenes or alkynes in the presence of dibutyl disulfide afford the desired bi- or tricyclic products with 54–88% yield (Scheme 2) [6]. In 2014, Maruoka

• [3 + 2] methylenecyclopentane annulations of olefins with methylenecyclopropanes. This regioselective, mild, and protecting group-free annulation requires only an equimolar amount of the reacting alkene and does not require an excess of the reacting alkene, unlike other methods [9]. Furthermore, the

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• isomer is marked with a star. 19F NMR yields are reported. a CH3CN/CH2Cl2 3:2, 0.08 M; b CH3CN/CH2Cl2 1:1, 0.05 M; c CH3CN/CH2Cl2 5:3, 0.05 M; d CH3CN/CH2Cl2 3:2, 0.02 M; e CH3CN/CH2Cl2 5:4, 0.057 M. Reaction optimization under flow conditions. Influence of bases on the photoredox trifluoromethoxylation

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• decarboxylation and [3 + 2] cycloaddition take place in the ternary complex, whereas such a reactivity from bulky adamantane 3 is less likely. This proof of principle that decarboxylation and cycloaddition can be performed in the β-CD cavity has a significant importance for the design of new supramolecular

• systems for the control of photoreactivity. Keywords: [3 + 2] cycloadditions; β-cyclodextrin; inclusion complexes; photochemistry; phthalimides; Introduction Cycloadditions are highly useful reactions in organic synthesis providing complex cyclic structures from easily available precursors [1][2]. Among

• different reactions, [3 + 2] cycloadditions showed applicability in the synthesis of heterocyclic 5-ring compounds [3], as well as in the green synthesis of a number of natural products [4]. One of the useful synthons in [3 + 2] cycloadditions is azomethine ylide [5][6][7], also used in intramolecular

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• thioketones reacted with donor–acceptor cyclopropanes in dichloromethane at room temperature in the presence of catalytic amounts of Sc(OTf)3 yielding tetrahydrothiophene derivatives, products of formal [3 + 2]-cycloaddition reactions, in moderate to high yields. In all studied cases, dimethyl 2

• thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone. Keywords: [3 + 2]-cycloaddition reactions; donor–acceptor cyclopropanes; ferrocenyl

• by means of spectroscopic methods (R = CF3). In a recent work, an alternative, efficient and useful method for the synthesis of highly functionalized tetrahydrothiophenes of type 6 was reported [9] (Scheme 2). Under Lewis acid catalysis, formal [3 + 2]-cycloadditions of aromatic and cycloaliphatic

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• Two kinds of [3 + 2] cycloaddition intermediates generated from the three-component reactions of 2-bromobenzaldehydes and maleimides with amino esters or amino acids were used for a one-pot N-allylation and intramolecular Heck reactions to form pyrrolidinedione-fused hexahydropyrrolo[2,1-a

• ]isoquinolines. The multicomponent reaction was combined with one-pot reactions to make a synthetic method with good pot, atom and step economy. MeCN was used as a preferable green solvent for the reactions. Keywords: [3 + 2] cycloaddition; Heck reaction; hexahydropyrrolo[2,1-a]isoquinoline; one-pot reactions

• related to natural products [18][19][20]. Among the well-established MCRs, three-component 1,3-dipolar cycloadditions of benzaldehydes, maleimides, and amino esters have been developed for making N-containing 5-membered heterocycles (Scheme 1) [21][22]. The [3 + 2] cycloadditions of maleimides with