Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• Jun Kikuchi Roi Nakajima Naohiko Yoshikai Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan 10.3762/bjoc.20.79 Abstract A stereoselective N-alkenylation of azoles with alkynes and iodine(III) electrophile is reported. The reaction

• between various azoles and internal alkynes is mediated by benziodoxole triflate as the electrophile in a trans-fashion, affording azole-bearing vinylbenziodoxoles in moderate to good yields. The tolerable azole nuclei include pyrazole, indazole, 1,2,3-triazole, benzotriazole, and tetrazole. The iodanyl

• group in the product can be leveraged as a versatile synthetic handle, allowing for the preparation of hitherto inaccessible types of densely functionalized N-vinylazoles. Keywords: alkynes; azoles; cross-coupling; hypervalent iodine; Introduction N-Functionalized azoles are prevalent in bioactive

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• suppressed the targeted reaction. Merely traces of the N–H insertion product were detectable in NMR data, with insignificant conversion of the initial heterocycle. Examples of N–H insertion reactions with azoles containing non-equivalent nitrogen atoms deserve separate discussion. As the only product of the

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• reactions with azoles and amines (Figure 1B) are also well-precedented [10]. Herein, we address a critical gap in the literature and report the discovery of a cycloaddition of gem-difluoroalkenes and organic azides mediated by a base and with morpholine as a solvent. The cycloaddition adducts, 1,4,5

• been reported to facilitate the addition of azoles to gem-difluoroalkenes (Figure 1B) [9][33]. An elevated temperature (110 °C) was required along with 48 h reaction time (Table 1, entry 3 vs entry 4) due to the sluggish nature of the reaction and poor reactivity of the gem-difluoroalkenes. The

• and beyond. The Z-geometry of INT-1 was determined from its 3JH−F coupling constant of 35.7 Hz in the 1H NMR with a matching J value in the 19F NMR. This is in agreement with Cao’s report on the geometry of N-(α-fluorovinyl)azoles [33]. The configurations of the E- and Z-isomers were determined by

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• amidating reagent leading to the isolation of copper–arylcarbamato species and the desired product. The developed amidation protocol works highly efficiently and selectively over a broad range of substrates including polyfluorobenzenes, azoles, and quinoline N-oxides (Scheme 74). 2.10 C(sp2)–H thiolation

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• the same year, Correa et al. reported the FeF2-catalyzed direct α-arylation of azoles with ethers (Scheme 25) [86]. This approach was suitable for assembling a wide variety of functionalized heterocycles, representing an attractive strategy for the C–H alkylation of azoles. The authors also discussed

• -catalyzed formation of 1,1-bis-indolylmethane derivatives. Alkylation of coumarins and flavonoids. Direct CDC α-arylation of azoles with ethers. CDC of terminal alkynes with C(sp3)–H bonds adjacent to oxygen, sulfur or nitrogen atoms. Alkylation of terminal alkynes. Co-catalyzed functionalization of glycine

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• benzylic substrates with azoles was developed [128] (Scheme 27). In the proposed mechanism DDQ participated in benzylic C–H bond cleavage. The C–N bond of the final product is formed as a result of the nucleophilic attack of azole on a benzylic cation. A two-fold molar excess of azoles was used. A

• oxidative organocatalysis. Electrochemical DDQ-catalyzed intramolecular dehydrogenative aryl–aryl coupling. DDQ-mediated cross-dehydrogenative C–N coupling of benzylic substrates with azoles. Biomimetic o-quinone-catalyzed benzylic alcohol oxidation. Electrochemical synthesis of secondary amines by

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• with various carbonyl compounds, such as carboxylic acid derivatives or aldehydes [6][7][8][9]. These classic reactions require harsh conditions, such as using strong acids or high temperatures. The syntheses of azoles using one-pot reactions are attracting increasing attention as alternatives to

• constructing azoles with an amine functional group at the 2-position, such as benzoxazole or benzoimidazole, but are unsuitable for the syntheses of 2-arylated or 2-alkylated benzoxazoles and benzimidazoles. In fact, only two reports cover the subject. Jackson et al. carried out the intramolecular ring-closure

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• Plasmodium has been developed and is reported in the literature [24]. Results and Discussion The vinylic SN reaction of 2-nitroperchlorobutadiene (1) with four equivalents of the azoles such as 1H-pyrazole, 1H-1,2,4-triazole, or 1H-benzotriazole affords similarly to [25] the corresponding 1,1

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• -resolved 1H,15N (JHN) and 13C,15N (JCN) coupling constants, as well as additional splitting of the corresponding signals in the standard proton decoupled 1D 13C NMR and 1D 1H NMR spectra [41][42]. The 1H,15N coupling constants in the azoles, especially the rather large 2JHN values, which are in the range

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

• aliphatic alcohols. In 2015, Ackermann’s group [88] disclosed the visible light-induced copper-catalyzed arylation of azoles. In this case, the mechanistic studies revealed that amino acid ligands accelerated the cross-coupling (Scheme 22). In 2020, a visible-light-induced copper-catalyzed arylation of C

• (sp2)–H bonds of azoles was developed by Zhang [89]. A 2,2’-bipyridine copper coordination compound served as the photoredox catalyst and accomplished the azole C–H arylations. Under irradiation with blue LED, the photoexcited state [LnCuI-benzoxazole]* (C) engages in a double electron-transfer process

• . Aerobic oxidative C(sp)–S coupling reaction. Copper-catalyzed alkylation of carbazoles with alkyl halides. C–N coupling of organic halides with amides and aliphatic amines. Copper-catalyzed C–X (N, S, O) bond formation reactions. Arylation of C(sp2)–H bonds of azoles. C–C cross-coupling of aryl halides

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

• powerful nitrogen source for the synthesis of various N-heterocycles, such as isoquinolines, quinolines, pyridines, pyrroles, indoles, azoles, and azepines [40][41][42][43][44][45]. 1,3-Enyne, as a powerful Michael acceptor, is a wonderful synthon for the synthesis of N-heterocycles via tandem addition and

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• , respectively (Table 2, entry 3). Apart from the 1H-indazole scaffold [36][37], the steric influence of adjacent substituent(s) on N-alkylation regioselectivity has previously been described for other nitrogen-containing heterocycles, such as pyrazole [38], purine, and related 1,3-azoles [39]. Although the N

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

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

• synthesis of new functionalized 1,2,3-triazoles. Keywords: azoles; cycloaddition; enones; heterocycles; 1,2,3-triazoles; Introduction 1,2,3-Triazoles are significant non-natural heterocyclic scaffolds with extensive applications in biochemistry, agrochemistry and materials chemistry [1][2][3][4][5]. This

• azides and alkynes [14][15]. However, the formation of the nitrogenated azoles by the classical Huisgen methodology is slow due to its high activation energies and also lack of regiochemical control, in general, leading to a mixture of 1,4- and 1,5-regioisomers of 1,2,3-triazoles. Later, Sharpless and

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

• , the synthesis of C8-phosphonates of 7- and 9-deazapurines via C–H phosphonation has been reported [17]. On the other hand, azolylpurines are an important compound class that combines two recognized structural motifs of drug design – purines and azoles. Derivatives of this class are known for their

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

• , rich chemistry and technically useful properties of heterocyclic compounds have made them a focal point of science and industry over the years. Heterocyclic compounds including azoles and azines have been found in natural products, and they are included in the structures of nucleic acids, vitamins

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

• for the introduction of a hexafluoroisopropyl group based on the reaction of tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding azoles [17]. Since this methodology is simple and works for a wide variety of imidazoles, including benzimidazole, we decided to explore the applicability of

• of the reaction of tetrakis(trifluoromethyl)-1,3-dithietane (1) with the azoles 2–7 is not entirely clear. Although there are two similar reactions reported in the literature (the reaction of 1 with anilines [18] and azoles [17]), no satisfactory mechanism was suggested for these reactions. Recently

• into the final product, with extrusion of elemental sulfur) is not well understood and may be more complex, involving additional steps. The mechanism clarification of the reaction of tetrakis(trifluoromethyl)-1,3-dithietane (1) with azoles (and anilines) does require further investigation. As was

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

• azoles. His research group discovered that the abundant and inexpensive CuI catalyst allowed the direct arylation of benzoxazoles under UV-photoactivation (Figure 46) [106]. Remarkably, this totally site-selective photoinduced C–H arylation took place at room temperature and the use of amino acid ligands

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• kJ/mol). Among the 1,3-azoles 15 is thermally the most labile one with a Tpeak of 118.9 °C. For an improved overview of the discussed ΔHdec values a graphical comparison sorted by the respective coordinating unit is given in Figure 4. After obtaining decomposition energies and temperatures for these

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• in monomeric form in the case of sterically crowded parent amines such as 1-aminoadamantane or tert-butylamine or, alternatively, as trimeric hexahydro-1,3,5-triazines 3’ in the case of sterically less crowded amines [7]. In analogy to other azoles and in contrast to six-membered aromatic N

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• C–H carbonylation. Hydroarylation by C–H activation. Pathways for cobalt-catalyzed hydroarylations. Co-catalyzed hydroarylation of alkynes with azobenzenes. Co-catalyzed hydroarylation of alkynes with 2-arylpyridines. Co-catalyzed addition of azoles to alkynes. Co-catalyzed addition of indoles to

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

• easy generation of anionic ligands from azoles, the same group described the preparation of neutral platinum(II) complexes resulting from the combination of dianionic with neutral chelates (Figure 4) [27]. Compounds 8 and 9 were weakly emissive in solution. Nevertheless, the solid-state emission of

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• showed lower efficiency. Then, they extended the substrate scope to 1,3-azoles and perfluoroarenes. Di-tert-butyl peroxide was chosen as a suitable oxidant instead of air. Functional groups, such as chloro and bromo, were compatible in this reaction, providing a complementary platform for further