Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• (Danheiser method [22]) or ethoxalylation [23]. Fortunately, all of the substrates 11a–s were converted cleanly and smoothly over 2–5 days into their diazo derivatives 10a–s using p-(acetamido)benzenesulfonyl azide (p-ABSA) as the diazo group donor [24] and DBU as the base. The yields of diazo compounds 10

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• diverse α-azidoketones in good yields without the use of a stoichiometric amount of chemical oxidant. A range of functionality is shown to be compatible with this transformation, and further applications are demonstrated. Keywords: azide; azidoketone; electrosynthesis; enol acetate; radical

• development of a green, efficient, and sustainable protocol for the synthesis of azidoketones is of great significance [7][8][9]. Retrosynthetically, the nucleophilic substitution of α-bromoketones by sodium azide [10] and oxidation of the azido alcohols [11] are among the most straightforward methods to

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• [24]. Both monomesityl and dimesitylphosphinyl azides 14 generated 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 15 in 31% and 20%, respectively, via an intramolecular nitrene C–H insertion, for dimesitylphosphinyl azide (14b), with 51% yield of phosphonamidate 16 as byproduct. Bis(2,4,6

• -triisopropylphenyl)phosphinyl azide (17) gave the corresponding 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxide 18 in 51% and phosphonamidate 19 in 28% yield (Scheme 4). The synthetic method was applied occasionally [24]. P-Stereogenic 3-arylmethylidene-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 21 and 23 were

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

• –Prakash reagent (TMSCF3) in the presence of Cs2CO3 as base in MeCN at 0 °C gave product 7 with a trifluoromethyl group. Stefani et al. reported the 1,3-dipolar azide–alkyne cycloaddition (AAC) of organotellanyl alkynes with organic azides in the presence of a copper reagent to form 5-organotellanyl-1,2,3

• -triazoles [33]. Based on these findings, we examined the reaction of Cu-mediated AAC. The reaction of 4aa with benzyl azide in the presence of one equivalent of CuI and pentamethyldiethylenetriamine (PMDETA) in THF at 60 °C gave the desired 5-selanyl-1,2,3-triazole 8 in 72% yield. This reaction yielded a

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• coupled with in situ generation of the azide from the corresponding bromide. The 1,2,3-triazoles are formed in up to 99% yield and in less than 10 minutes residence time, which includes azide formation prior to the cycloaddition step. Interestingly, this process could not be successfully repeated under

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• able to build a new catalytic machinery [100]. Hereunto, the two concepts RPI and ILC were combined in a synergistic manner, starting with rotor [Cu2(83)(91)]2+ (k298 = 46.0 kHz) that catalyzed the click reaction between the zinc porphyrin ligand 92 and the azide 93 furnishing triazole 94 (Figure 20

• porphyrin 92 is catalytically inactive. However, upon addition of azide 93, the formation of [Cu2(83)(91)(94)2]2+ was detected. Since the organocatalyst originally firmly bound at the ZnPor of ligand 92 is now part of the dynamic slider-on-deck [Cu2(83)(91)(94)2]2+, the motion of biped 83 will dynamically

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• could be regarded as a protective group by shielding the internal alkenyl site. In 2016, the Rebek group achieved the site-selective reduction of an α,ω-diazide compound by trimethylphosphine (PMe3) in aqueous solution with a cavitand host as the protecting group for one of the azide sites (Figure 5

• the complex solution with three equivalents of PMe3 resulted in the reduction of one of the azide groups. At this stage, the monoamine guest showed a fixed unsymmetrical J-shaped conformation with the amine end exposed and the azide end deeply protected inside the cavitand. The addition of another 3

• equivalents of PMe3 to the post-reaction mixture after 24 hours still did not induce further reduction of the residual azide group. However, control experiments gave just the diamine products. This work opened the protective ability of water-soluble cavitands and inspired many other following examples of

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• isocyanides 3 produced the azide intermediates 4, which were treated sequentially with triphenylphosphine, isocyanates (or CS2), and secondary amines to give polysubstituted 3,4-dihydroquinazolines 8 and 4H-3,1-benzothiazines 11 in good overall yields through consecutive Passerini/Staudinger/aza-Wittig

• -azidobenzaldehyde (1a), benzoic acid (2a) and tert-butyl isocyanide (3a) as the reactants (Scheme 2). When a mixture of 1a, 2a, and 3a in CH2Cl2 was stirred at room temperature for 48 h, the three-component Passerini reaction was carried out smoothly and the azide 4a (R = Ph) was finally obtained in 87% yield

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• sialic acid derivatives in good yields and high purity via copper-catalysed azide–alkyne cycloaddition (CuAAC, click chemistry) and evaluated their activity towards TcTS and neuraminidase. Surprisingly, the compounds showed practically no TcTS inhibition, whereas ca. 70% inhibition was observed for

• ) has also been introduced at C-2 of α-triazole-linked sialic acid derivatives modified at C-9 as ligands for the transmembrane glycoprotein CD22 [21]. In this sense, we have synthesised a small series of 1,2,3-triazole-linked sialic acid derivatives via copper-catalysed azide–alkyne cycloaddition

• acid derivatives was synthesised as outlined in Figure 2B. Emulating our previous work with anomeric azide CuAAC click chemistry [17][22][23][24], the well-known α-azidosialic acid 1 [25] was synthesised from N-acetylneuraminic acid in four steps [26] in good overall yield (55%). The assignment of the

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• eventually brought about the need for newly designed and improved anti-HIV drugs with respect to their improved pharmacological properties [20]. With an idea to keep the presence of azide functionality and to introduce structural rigidity, Marquez et al. [21] developed a methodology for the synthesis of

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• the epoxide-ring-opening reaction of 7 with sodium azide, to introduce an extra amino group in position 4 on the cyclooctane skeleton. For this, epoxide 7 was treated with NaN3 in the presence of NH4Cl/DMF and this formed lactone 13 as the sole product in 80% yield (Scheme 4). The epoxide 7 was

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• with other nitrogenous nucleophiles, such as azide ions. The reaction of 18 in the presence of sodium azide and water produces 4-azido-1,2-naphthoquinone (39) in a 52% yield. Although 39 can produce many other derivatives, few reactions have been studied. The reaction of 39 with concentrated sulfuric

• involving the addition of arylamines to β-NQS 18 followed by N-alkynylation and then Cu(I)-catalyzed heterocyclization with tosyl azide in toluene at room temperature, leading to triazoles 50c–k in moderate to excellent yields (Scheme 14). The research group that most explored the formation of heterocycles

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• examining of other potential arenes capable of undergoing electrophilic aromatic substitution would expand the applicability of the reaction. Carboazidation In 2018, Yang investigated the three-component carboazidation of styrene derivatives 115 with alkanes 101/139b and trimethylsilyl azide for the

• carboazidation product was observed. In the same year, the Xu laboratory demonstrated Togni’s reagent could be employed for the synthesis of γ-azido fluoroalkanes [128]. In 2019, Chu and co-workers demonstrated the three-component carboazidation of alkenes with chloroalkanes and trimethylsilyl azide could be

• solvent-tuned [129]. In neat CH2Cl2, the reaction produced the expected β-trichloromethyl alkyl azide; however, the reaction was chemoselective for diazidation when tert-butanol was used as co-solvent. The authors hypothesized the presence of the alcohol suppresses the polar-unmatched HAT process from

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• mmol) in dry THF (10 mL) was cooled in an ice-water bath, and subsequently, diisopropyl azodicarboxylate (DIAD, 1.21 g, 6.0 mmol) and diphenylphosphoryl azide (DPPA, 1.65 g, 6.0 mmol) were added dropwise under argon atmosphere. The mixture was allowed to reach room temperature and stirred for 20 h. The

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• tetrazoles from bile acid precursors was developed. Mild reaction conditions using TMSN3 instead of hydrazoic acid as an azide source produced good yields of the desired tetrazoles. These conditions could be applied to other steroidal precursors. Additionally, an improved methodology for the synthesis of

• selective activity towards certain tumor cell lines. Keywords: antiproliferative activity; Schmidt reaction; steroids; tetrazoles; trimethylsilyl azide; Introduction Bile acids are naturally occurring steroidal surfactants that play various biological roles. Besides the well-known role as lipid

• ]. The main approach in the synthesis of the tetrazoles is 1,3-dipolar cycloaddition between azide and nitrile. These reactions often follow the principles of “click” chemistry [20]. Although the formation of tetrazole in the Schmidt reaction of ketones was noted in the original study by Schmidt himself

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• arenes (Scheme 13). In this transformation, the azide anion is oxidized to its radical, and this process requires a high reduction potential that cannot be achieved by iridium and ruthenium-based catalysts. In contrast, [Cu(dap)2]Cl and [Cu(dap)Cl2] were found suitable for the oxidation. Based on a

• mechanistic study, CuII serves as the catalytically active species that undergoes homolytic cleavage to form a CuI species and an azide radical. The latter adds to the alkene to form an alkyl radical, which is then trapped by oxygen to form the desired product. The homolytic cleavage of the active species

• represents a new platform for copper-based photocatalysis (see section 3.3). In 2019, Yu et al. [64] developed a similar copper-catalyzed azidation of activated alkenes with 1-azido-1,2-benziodoxole as the azide radical precursor (Scheme 14). 3.3 Functionalization of alkynes A series of photoinduced copper

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• , Turkey King Abdulaziz University, Faculty of Science, Chemistry Department, 21589 Jeddah, Saudi Arabia 10.3762/bjoc.17.164 Abstract The development of long-wavelength photoinduced copper-catalyzed azide–alkyne click (CuAAC) reaction routes is attractive for organic and polymer chemistry. In this study

• azide derivatives under both white LED and NIR light irradiation. Due to its deeper penetration of NIR light, the possibility of synthesizing different macromolecular structures such as functional polymers, cross-linked networks and block copolymer has also been demonstrated. The structural and

• [40]. BPNs were tested as NIR photoinitiator for the CuAAC reactions of low molar mass compounds and polymers possessing antagonist azide and alkyne functionalities (Figure 1). The optical absorption spectra of BPNs, copper(I) chloride (CuICl, 0.05 mmol) and copper(II) chloride (CuIICl2, 0.05 mmol

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• intramolecular nucleophilic attack by azide and the following deprotonation by a fluoride anion provide the final product 8 (Scheme 5). The derivatization of sulfonated aminonicotinates 8 could easily be achieved. Desulfonylation of aminonicotinate 8b proceeded smoothly in the presence of triflic acid (2.0 equiv

• generate intermediate 20. Then, the intramolecular nucleophilic attack by azide and the following deprotonation give the final product 18 or 19, respectively. 5‑Selenyl- and 5-sulfenyl-substituted nicotinates can carry out versatile transformations, which have potential application in pharmaceutical

• -nitro-1,3-enynes 34 with amines, and trimethylsilyl azide (TMSN3, Scheme 16) [61]. The reaction could be carried out efficiently in the presence of 2.0 equiv of Cu(OAc)2·H2O. Interestingly, the addition of 10 mol % MnCl2 could promote the reaction more smoothly. A wide range of substituted aromatic

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• obtained from the nucleophilic substitution reaction of intermediate 8 in 85% yield. The 1H and 13C NMR spectra of compounds 8 and 9 were similar, but in the IR spectrum of intermediate 9, it was possible to observe the characteristic stretching of the azide group at 2103 cm−1. The 1,3-dipolar

• products 1a,b, and 2a–j, respectively, with 30–84% yields. This last step was adapted from a method already described in the literature [31]. The formation of compounds 1a,b and 2a–j was observed by the disappearance of the characteristic stretching of the azide groups at 2107 and 2103 cm−1 in the IR

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

• 3-amino-2-naphthoic acid (97) to a Sandmeyer reaction and obtained 98. Then, a Curtius rearrangement of 98 by using diphenylphosphoryl azide (DPPA) yielded 3-iodonaphthalen-2-amine, that was subjected to a Suzuki cross-coupling with potassium vinyltrifluoroborate resulting in aminostyrene 99. The

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

• used in a [2 + 2] glycosylation, affording the tetramer 74 with an alternated N-acetyl pattern (Scheme 11A) [257]. Partially N-acetylated COS dimer and tetramer were obtained exploiting the orthogonality of the azide and N-Troc groups [258]. β-Selectivity during the glycosylation with the C-2 azido

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

• compounds in excellent yields and short reaction times (Scheme 21B and C). The robustness of the manganese-catalyzed photo-flow reaction was demonstrated by a gram-scale preparation of the key intermediate in the synthesis of the pharmaceutical compound dantrolene (60) in high yields (Scheme 21D). The azide

• variety of functionalized compounds, from arylated compounds to new azide substances. This is an important characteristic in the synthesis and evaluation of biologically active molecules, since using different methods, a large variety of potential compounds can be obtained and studied. Larger scopes

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• attempt to introduce high yielding phosphoramidite building blocks suitable for automated ON synthesis, 2′-O-aminoethoxymethyl and 2′-O-aminopropoxymethyl nucleotides were developed. This method introduced the primary amine functionality through an azide reduction [73]. The corresponding monomers 37 and

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

• azidation product 11. Upon regeneration, the catalyst participates in the next catalytic cycle. In this Mn-catalyzed azidation study, the azide/oxygenated product ratio was 2:1–4:1. Therefore, a chemoselective manner is of dire need to avoid unwanted C–H oxygenation. In 2020, the Lei group disclosed the

• and loxoprofen underwent regioselective azidation at the secondary benzylic sites over tertiary benzylic sites (see 13d and 13e). Additional mechanistic studies support the reaction pathway depicted in Figure 4. The azide anion is oxidized to a radical species on the anodic surface, where Mn(II)/L–N3

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116