Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• trichloroacetimidate donor 75 was controlled by SN2 displacement of the α-trichloroacetimidate LG upon activation with BF3·OEt2 in CH2Cl2/n-hexane (3:2) (Scheme 11B). The orthogonal N-trichloroacetyl (N-TCA) and N-benzyloxycarbonyl (N-Cbz) PGs permitted the synthesis of chitobioses with different PA. N-TCA groups

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• and colleagues proposed an asymmetric [3 + 2] cycloaddition employing a coumarin dipolarophile 43 with azomethine ylides 60 organocatalyzed by quinidine (62) for the formation of fused pyrrolidine compounds through activation of the coumarin substrate by hydrogen bonding [53]. The methodology enabled

• addition in the least hindered Re face, consequently resulting in products of (R)-configurations, which were determined via X-ray crystallography. A stereoselective [3 + 2] cycloaddition with indandione alkylidenes 103 and 3-homoacylcoumarin 70 as the 1,3-dipole precursor, to generate a series of coumarin

• hydroxylated malonate 53 catalyzed by NHC 55. Oxidative [4 + 2] cycloaddition of enals 57 to coumarins 56 catalyzed by NHC 59. Asymmetric [3 + 2] cycloaddition of coumarins 43 to azomethine ylides 60 organocatalyzed by quinidine 62. Synthesis of α-benzylaminocoumarins 64 through Mannich reaction between 4

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

• similar catalyst, [Sc-2], which bears a more electron-rich cyclopentadienyl ligand, in a scandium-catalyzed C–H [3 + 2] cyclization (Scheme 5B) [40]. In this transformation, several aminoindane derivatives were obtained from benzylimines in the presence of the catalyst [Sc-2], alkenes and [Ph3C][B(C6F5)4

• benzylic, allylic, 3°, 2°, and 1° aliphatic, using unsubstituted linear sulfamate esters (Scheme 17A and B) [130]. This method is also compatible with substrates containing adjacent substituents like protected amines and tolerates the presence of electron-withdrawing groups as well as α-substituted alkynes

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• conjugative transformations, such as azide–alkyne [3 + 2]-cycloaddition [30][31][32][33][34][35][36][37]. Based on their previous late-stage fluorination studies [22][25], Groves et al. further showcased a manganese(III)–salen-catalyzed azidation process using an aqueous azide solution as a convenient azide

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• reactions [17], or in umpolung [3 + 2] annulations [18]. In all these cases, the reactions were performed without protective gas indicating that electronically modified arylphosphines tolerate the presence of oxygen. Herein we wish to report the scope of three different triarylphosphine catalysts in the oxa

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• industry. The current review aims to cover a wide literature survey of numerous synthetic strategies. Recent reports (2017–2021) in the field of 1,4,5-trisubstituted 1,2,3-triazoles are emphasized in this current review. Keywords: azides; Click reaction; [3 + 2]‐cycloaddition; fully functionalized 1,2,3

• catalyst with the corresponding acetylide by using LiOt-Bu. Further intermolecular [3 + 2]-cycloadditions of azide 67 with intermediate 70 affords a 5-copper(I)-substituted triazolide intermediate 71. The oxidative addition of 1-bromoalkyne 68 forms an alkyne–Cu(III)Br–triazole complex intermediate 72

• a [3 + 2]-cycloaddition between alkynes 73 and 76 and alkylthiotosyl azides 74 using MeOLi in the presence of a copper(I) catalyst in dioxane at room temperature. This Click/intramolecular sulfenylation reaction displayed an extensive scope, complete regioselectivity, and good to high yield of

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• fused pyrazole derivatives as the exclusive products. The reactions proceed via the initially formed [3 + 2]-cycloadducts, which undergo spontaneous aerial oxidation to give aromatized heterocyclic products. Only for 2,3,5,6-tetramethyl-1,4-benzoquinone, the expected [3 + 2]-cycloadduct exhibited fair

• naphthoquinone-derived products and low-intensity bands in the visible region (≈400 nm) for the anthraquinone series. Keywords: [3 + 2]-cycloadditions; fluorinated compounds; fused pyrazoles; N-heterocycles; nitrile imines; 1,4-quinones; Introduction The 1,4-quinone scaffold belongs to the most important

• , [3 + 2]-cycloadditions leading to five-membered heterocycles are less often employed in spite of the high dipolarophilicity of the α,β-unsaturated diketone system [6][7][8][9]. Notably, in the already reported reactions of propargylic 1,3-dipoles, such as nitrile oxides or nitrile ylides, with 1,4

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• developed protocol doesn’t require column chromatography for purification of target compounds 3 and can be performed in a gram scale. Pyridinium bromides 1a–l,n–w and iodide 1m were prepared by the reaction of 3-(2-bromophenyl)-2H-azirine (4a) with substituted N-phenacyl pyridinium salts 5a–w according to

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• Jie Zheng Shuyu Meng Quanrui Wang Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, P. R. China 10.3762/bjoc.17.104 Abstract The treatment of 2-(2-vinylphenyl)acetaldehydes or 3-(2-vinylphenyl)propanals with BF3·Et2O results in an intramolecular Prins reaction

• formation of tetrahydro-5H-benzocyclohepten-7-ol ring systems. As shown in Scheme 8, the required homo-aldehyde substrate 19 was prepared starting from methyl 3-(2-bromophenyl)propionate (16) analogously as for 13. Reduction of the ester 16 with LiAlH4 in THF at 0 °C afforded the alcohol 17 that was

• subjected to a Suzuki reaction with pinacol vinylboronate using Pd(dppf)Cl2 as catalyst to produce 3-(2-vinylphenyl)propan-1-ol (18). The oxidation of alcohol 18 with Dess–Martin oxidizing reagent furnished the requisite aldehyde 19 in 43% yield over the three steps. Under the standard conditions, aldehyde

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• , alkyl N-arylideneglycinates have attracted much attention in recent years. For instance, the metal-catalyzed asymmetric [3 + 2] cycloaddition of ethyl N-benzylideneglycinates with electron-deficient alkenes has been reported to yield substituted pyrrolidines [30]. Recently, we reported the synthesis of

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

• -pyrrolines 82 were formed as single diastereomers [101]. The whole process could be considered a [3 + 2] annulation, and aziridines were not observed as competing reaction products (see above Scheme 11). In addition, hindered imines, ethers, sulfonates, heteroaryl substituents, and conjugated imines were all

• one of the most important points, continue to be of great interest [109][116][117][118]. Cyclizations involving a position in the starting chiral imine Enantiomeric N-tert-butanesulfinyl imines 104b derived from 3-(2-bromophenyl)propanal have been used as reaction intermediates in the synthesis of

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• ] developed a visible-light-induced [3 + 2] cycloaddition reaction between glycine derivatives 57 and aryl epoxides 58, which can efficiently prepare a series of multisubstituted 1,3-oxazolidines 59 at room temperature (Scheme 20). The strategy can be applied smoothly to an extensive range of glycine

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• , these diazo compounds undergo [3 + 2] cycloadditions with suitable substrates to render various nitrogen-rich heterocycles [39]. In addition to their synthetic importance, these are frequently encountered as ligands in many metal complexes [40][41][42][43]. Our group have also employed 1,3-dicarbonyl

• alternative approach for the synthesis of such triazole moiety 3a is the [3 + 2] cycloaddition between alkynes and the corresponding azides. However, the major disadvantage of such a strategy is the use of 3-azidoenone which is difficult to handle owing to its explosive nature. Therefore, our method provides

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• treatment of the resulting 2-(pyrrol-3-yl)aniline 25 with 3-(2-bromophenyl)propyl isocyanate (26a), which afforded urea 27a in 60% yield. The treatment of urea 27a with CBr4 and PPh3 in the presence of Et3N then gave carbodiimide 28a in a good yield of 74%. Following the reaction of 28a with TBAF in 1,2-DCB

• -aminopyrroloquinoline 30b was synthesized from 2-(pyrrol-3-yl)aniline 25 and 3-(2-iodophenyl)propyl isocyanate (26b) in 3 steps using the same procedure as described for 30a. The subsequent cycloamination of 30b gave tetrahydroquinoline 31 in 73% yield, thus resulting in a significantly improved yield. Finally, the

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• -(aminoxy)-γ-(silyloxy)amides 9l–p with cyclic units are also suitable precursors for radical cyclization reactions (Scheme 3). 3-(2-Hydroxycyclohexyl)-2-pyrrolidone 12l was obtained by the thermal cyclization of α-(aminoxy)cyclohexylacetamide 9l as a mixture of two major trans isomers 12lA and 12lB, which

• were accompanied by traces of a C3–C4 cis-diastereomer (not shown). The relative configuration of pyrrolidone 12l was assigned by NOE experiments of 3-(2-oxocyclohexyl)lactams 13l prepared from 12l by Dess–Martin oxidation (vide infra). The thermal cyclization of compounds 9m,n with N

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• includes a [3 + 2] click reaction between the azide ion with the triple bond and further C–N coupling instead of the IAAC reaction. Compounds having no fused benzene ring or with a heterocyclic moiety instead could also be obtained via the tandem approach Ugi reaction/IAAC [15][16]. Despite the

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• ). The recovered solid catalyst was washed with acetonitrile (3 × 2 mL) and dried in an oven (150 °C, 1 h) for its reuse. TEM micrograph and size distribution graphic for CoNPs@MgO catalyst (scale bar = 20 nm). Plausible mechanistic pathway for olefin epoxidation catalyzed by CoNPs/MgO in the presence of

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• mL column was suspended in 5 mL of DMF and swollen overnight. After washing with DMF (3 × 2 mL), the Fmoc groups of the Rink amide AM resin were activated with 20% of piperidine in DMF (2 mL) for 20 min. After washing with DMF (3 × 2 mL), Fmoc-Ser(t-Bu)-OH (3 equiv) as the first Fmoc-amino acid and

• the mixture of HBTU, HOBT, and DIPEA (3 equiv/3 equiv/6 equiv) in DMF were added to the resin and shaken for 30 min. The reaction was monitored using a Kaiser test based on the reaction of ninhydrin. After washing with DMF (3 × 2 mL) and DCM (3 × 2 mL), 25% of acetic anhydride in DCM (2 mL) was added

• capping the reaction with 25% of acetic anhydride in DCM (2 mL), the column was washed with DCM (3 × 2 mL), DMF (3 × 2 mL), and methanol (3 × 2 mL), and dried overnight. A solution of 2.5 mL of TFA/TIS/H2O 94:2.5:2.5 (v/v/v) was added to the column for cleaving the compound from the resin, and the

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• , conveniently prepared by [3 + 2] cycloadditions of terminal alkynes with sulfonyl azides, have been used as the precursors to N-sulfonylindoles by transition-metal-catalyzed transannulation reactions. In the presence of Rh(II) or Ni(0) catalysts the triazole ring-opening takes place and intermediate highly

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