Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• first reported synthesis of pharmacologically interesting N-thiazolyl derivatives. Keywords: fused-ring systems; hydrazones; indazoles; intramolecular cyclization; N-heterocycles; Introduction 1H-Indazoles are important scaffolds due to the prevalence in compounds with biological activity [1], such as

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

• ]. Continuing our interest in the synthesis of N-heterocycles via the aza-Wittig reaction and multicomponent reactions [36][37][38], we wish to report herein a facile synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• )-ones 7 upon action of bis(trifluoroacetoxy)iodobenzene (PIFA) (see Scheme 1D). A part from the well-known applications of hypervalent iodine compounds for oxidative rearrangements, fragmentations, halogenations and hydroxylations [37][38], they were also involved in the synthesis of N-heterocycles [39

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• moderate yield with >90% enantioselectivity (Scheme 20c) and tolerable diastereoselectivity (4:1) [73]. The optically enriched benzimidazoles are N-heterocycles which are of great interest as drug-like molecules [75], and exhibit biological activities such as anticancer, antiviral, antifungal, and

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

• subsequent stereoselective transformations. In addition, Fimognari’s group [101] utilized copper photoredox catalysts to achieve the N-desulfonylation of benzenesulfonyl-protected N-heterocycles 72 (Scheme 29). In 2019, Xiao’s group [102] observed that under visible light or copper catalysis, cycloketone

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

• introduce the applications of the products and the reaction mechanisms for the synthesis of corresponding N-heterocycles. Keywords: 1,3-enyne; functionalization; pyridine; pyrrole; tandem annulation; Introduction The pyridine moiety is an important class of six-membered N-heterocycles that is widely found

• 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

• in Scheme 22). Conclusion 1,3-Enynes, one of the most significant classes of Michael acceptors for the construction of N-heterocycles, have been widely used in organic synthesis. We herein reviewed the recent advances in the development of tandem cyclization reactions of 1,3-enynes in the presence of

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

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

• -triazoles; N-containing heterocycles; 1,4,5-trisubstituted 1,2,3-triazoles; Introduction A high number of N-heterocycles [1][2][3][4] are identified, and this number is increasing very quickly [5][6][7][8]. Among them, the small heterocyclic ring of the 1,2,3-triazole is present in a broad variety of

• applications of these five-membered N-heterocycles are the result of both their easy synthetic procedures and ring functionalization [9][31][32]. Typically, 1,2,3-triazole derivatives are prepared via a 1,3-dipolar cycloaddition reaction between azides and alkynes [33]. It is worth noting that the metal

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

• 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

• reaction [42][43] but also via simple and highly efficient [3 + 2]-cycloadditions of nitrile imines with the C=C bond of 1,4-quinones. In general, the present study emphasizes the great importance of nitrile imines as versatile 1,3-dipoles useful for the preparation of N-heterocycles of potential

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• -rich N-heterocycles [2][3][4], decarboxylative cross-coupling reactions with propiolic acid derivatives [5], Michael addition reaction [6], cross-couplings catalyzed by Pd [7] and Cu salts [8][9], the preparation of symmetrical and nonsymmetrical disulfides [10][11], and the synthesis of β-acetamido

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• small group of structurally related N-heterocycles such as carbazole [5], dimethylacridine [13], phenoxazine [17], and phenothiazine [18]. Prior studies have shown that placing the donor groups ortho to the acceptor can lead to more limited conjugation between the two, resulting in emitters with

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• substrates. Keywords: DFT calculations; gold catalysis; Nazarov reaction; N-heterocycles; Introduction In the development of new and effective catalysts, step economy is surely one of the major goals. A reduction of the number of steps in the synthesis of complex compounds can be attained by cascade

• first step [1][9][10][11][12]. In the framework of our studies on gold(I)-catalyzed reactions of propargyl alcohol derivatives [13][14][15], we have recently reported that the pentannulation of N-heterocycles [16] can be efficiently achieved by a cascade gold-catalyzed [3,3]-rearrangement/Nazarov

• piperidine derivatives 1 because of the accelerating effect of the nitrogen atom that stabilizes the oxyallyl cation intermediate 4 formed upon the ring closure. This was in analogy to that found for the classical Brønsted or Lewis acid-catalyzed Nazarov reaction involving N-heterocycles [27][28][29][30][31

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• reaction times, and excellent isolated yields. The products do not require chromatographic purification, and the catalyst can be reused seven times. Therefore, the catalyst is a greener alternative for the synthesis of the above N-heterocycles compared to the existing reported catalysts. Keywords

• aforesaid nitrogen-containing heterocycles. Benzimidazoles are an important class of N-heterocycles due to their potential applications in both biology and medicinal chemistry [10][11][12][13]. These compounds are used in the treatment of diseases, such as obesity, ischemia-reperfusion injury, hypertension

• . Further, dolomite is used as a heterogeneous green catalyst in very few organic transformations, such as Knoevenagel, Michael–Henry, and transesterification reactions [73][74]. To the best of our knowledge, there are no reports on the NDL-catalyzed synthesis of aforesaid N-heterocycles under ultrasonic

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

• et al., allowing the synthesis of N-heterocycles such as indoles and pyrroles. The targeted heterocyclic products were obtained by cyclization of acetanilides with alkyne derivatives via a direct ortho-metalation pathway (Figure 17) [79]. Acetyl substituents acted as DG in this transformation

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

• )ethylene-1,2-dicarbonitrile (R = CF3) [8]. Both five-membered spirotetrahydrothiophenes 3 and seven-membered S,N-heterocycles (ketene imines) 4 were observed in the course of these reactions (Scheme 1). The latter products were trapped with suitable nucleophiles (R = CO2Me) or even isolated and identified

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• -Acr+ scaffold. In 2015, they developed a site-selective C–H amination of arenes (Scheme 25) [110]. The arenes 25.1 could be aminated by various N-heterocycles 25.2 for the synthesis of the C–H functionalization products 25.3 with fine-tuned Mes-di(t-Bu)Acr+ (OD4) as a photocatalyst. In this

• oxidation of 29.1 was achieved using Mes-Acr-Me+ (OD2) and a cobalt cocatalyst, ensuring an efficient dehydrogenation. Various N-heterocycles 29.3 were accessed via a radical cyclization cascade with the alkyne derivatives 29.2. Amidyl radical generation The oxidation of amides is more difficult compared to

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• oxabicyclic substrates with organolithium reagents (selected examples). Copper-catalysed ring opening of polycyclic meso hydrazines. Copper-catalysed ACA of Grignard reagents to alkenyl-substituted aromatic N-heterocycles. Copper-catalysed ACA of Grignard reagents to β-substituted alkenylpyridines. Copper

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• or fluoroalkyl groups into three-membered N-heterocycles has emerged as an attractive direction due to the unique fluorine effect in pharmaceuticals and biology [7][8][9][10][11]. In this context, it is not surprising that the syntheses of trifluoromethylaziridines have been pursued from versatile

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• , Pietermaritzburg 3201, South Africa 10.3762/bjoc.16.35 Abstract Diverse P,N-phosphine ligands reported to date have performed exceptionally well as auxiliary ligands in organometallic catalysis. Phosphines bearing 2-pyridyl moieties prominently feature in literature as compared to phosphines with five-membered N

• -heterocycles. This discussion seeks to paint a broad picture and consolidate different synthetic protocols and techniques for N-heterocyclic phosphine motifs. The introduction provides an account of P,N-phosphine ligands, and their structural and coordination benefits from combining heteroatoms with different

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• enormous range of applications in biology [121][122][123]. Inspired by other C–H arylation methods for N-heterocycles [124][125][126], recently, Guo and co-workers reported a dual photoredox-catalyzed C–H arylation of 6-arylpurine using photoredox catalyst 12a in the presence of a Pd cocatalyst [127]. With

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• results were rationalized based on docking studies. Keywords: Buchwald–Hartwig reaction; cyclization; N-heterocycles; palladium; Suzuki–Miyaura reaction; Introduction Furoindoles and their derivatives have received a lot of attention based on their versatile pharmaceutical activities. Furoindols were

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

• high Tpeak but also higher ΔHdec values for the latter ones. NHIs bearing N-heterocycles with a high N/C-ratio such as triazoles show among the lowest Tpeak and the highest ΔHdec values. A comparison of NHIs with known (pseudo)cyclic benziodoxolones is made and we further correlated their thermal

• promising properties in terms of reactivity and stability. However, iodanes stabilized by nitrogen-based ligands, in particular N-heterocycles are still underexplored [22][23][24][25][26][27][28]. Recently, our groups investigated systematically cyclic and pseudocyclic N-heterocycle-stabilized iodanes (NHIs

• ). We demonstrated that the N-heterocycle significantly influences the important I–L1 bond length and subsequently has a profound impact on the reactivity of the iodane in oxygen transfer reactions [29][30]. Since the combination of a highly oxidized hypervalent iodine species with N-heterocycles with a

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• ]. Additionally, a diverse range of N-heterocycles, amides and motifs commonly encountered in medicinal chemistry were used as handles to direct C–H fluorination for the synthesis of pharmaceutical drugs (Scheme 24) [25]. Copper catalysis Despite the success of Pd-catalyzed fluorinations, the more widespread use

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

• ; nucleophilic carbenes; sulfur transfer reaction; Introduction Imidazole N-oxides constitute a practically valuable class of five-membered aromatic N-heterocycles [1][2][3][4][5]. The subclass of 2-unsubstituted imidazole N-oxides 1 with diverse substituents located at N(1), C(4), and C(5) is of special

• 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

• -heterocycles, N-oxides 1 cannot be prepared via oxidation of the parent imidazoles by treatment with an oxidizing agent, e.g., with a percarboxylic acid [6]. Imidazole N-oxides are versatile substrates for the preparation of diverse imidazole derivatives and the most characteristic feature is their 1,3-dipolar