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

• ][12], inflammation [13], bacterial [14][15], and viral infections [16]. Hence, new ways to rapidly and efficiently access 1,2,3-triazole heterocyclic motifs are still in demand. However, methods for the direct synthesis of 1,4,5-trisubstituted-1,2,3-triazoles are limited [17]. This is highly desirable

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• classes of heterocyclic compounds studied for a long time. Those scaffolds have attracted great attention since the introduction of various glitazones and epalrestat into clinical use for the treatment of type-II diabetes (Figure 1). Indeed, those compounds are often identified as hits in high throughput

• . Surprisingly, 2-naphthaldehyde was found to be less reactive and needed a reaction time of 24 h to obtain product 3g with 85% yield. Heterocyclic aldehydes gave also good results as shown with pyrrole-2-carboxaldehyde that allowed formation of product 3h in 86% yield. Rhodanine-3-acetic acid also allowed

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• enantioselectivity and the product yield were reduced. Although, the authors did not further explain the catalytic pathway. The use of organocatalysts in sulfenylation of N-heterocyclic compounds was investigated by Gustafson′s group in 2017 (Scheme 48) [81]. In their work, a series of conjugate Lewis base Brønsted

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

• Nosheen Beig Varsha Goyal Raj K. Bansal Department of Chemistry, The IIS (deemed to be University), Jaipur, 302 020, India 10.3762/bjoc.19.102 Abstract N-Heterocyclic carbenes (NHCs) are a special type of carbenes in which the carbene carbon atom is part of the nitrogen heterocyclic ring. Due to

• addition; [3 + 2] cycloaddition reaction; hydrosilylation reaction; N-heterocyclic carbenes; NHC–Cu complexes; NHC–Cu complexes as catalyst; Introduction N-Heterocyclic carbenes (NHCs) are a neutral species having the carbene carbon atom as a part of the nitrogen heterocyclic ring. The transient

• reaction of the carbene 1,3-dimesitylimidazol-2-ylidene (7a) with carbon tetrachloride in THF (Scheme 4) [5]. Structure of N-heterocyclic carbenes N-Heterocyclic carbenes contain at least one nitrogen atom and there may be another nitrogen atom or a sulfur atom present in the heterocycle. A general

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• state, in good yield. Keywords: alkynylation; catalysis; cyclization; indoles; iodination; multicomponent reactions; Introduction Indoles and their derived substitution patterns are omnipresent heterocyclic structural motifs in nature [1], many natural products [2][3], drugs [4][5][6][7][8], and dyes

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

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

• oxidant (Scheme 38a) [103]. Subsequently, Li et al. developed the CDC of heterocyclic aromatics with simple ethers mediated by AgOTFA to construct C(sp2)–C(sp3) bonds. The reaction proceeds under mild conditions (room temperature) with a wide range of substrates (Scheme 38b) [104]. The reaction mechanism

• heterocyclic aromatics with α-C–H bonds of ethers was achieved under the irradiation of a 34 W blue LED using rose bengal (RB) as the organic photoredox catalyst, TBHP as oxidizing agent, and DABCO as the base (Scheme 43c) [125]. The wide scope of substrates, aerobic conditions, and gram-scale suitability are

•  43d) [126]. Further, in the presence of [Ir{dF(CF3)ppy}2(dtbbpy)]PF6 as a photocatalyst, Na2S2O8 as oxidant, and TFA as an additive, under the irradiation of 26 W CFL at room temperature, the CDC reaction of various heterocyclic aromatics with α-C(sp3)–H bonds of ethers could be accomplished (Scheme

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• . This reaction has the advantages of using readily available materials, simple reaction conditions, satisfactory yields, high diastereoselectivity and atomic economy, which enable this reaction potential synthetic applications in heterocyclic chemistry and medicinal chemistry. Experimental General

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• carbazole heterocyclic oxidation products [75]. LOHC compounds could potentially provide both protons and electrons for artificial photosynthesis. The thermodynamics of electrochemically hydrogenating several LOHCs using a modified water-splitting device have been investigated [40]. However, other

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

• pyrroles was applicable to electron-poor aryl halides including various heterocyclic halides, affording their products in poor to excellent yields (4–92%) (Figure 9A). Regarding the unsatisfactory results, the coupled products of the strongly deactivated 4-bromoanisole (Epred = −2.75 V vs SCE) and 4

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• rearrangement; 1,3-thiazines; thiazolidine-4-ones; Introduction Nitrogen- and sulfur-containing heterocyclic compounds are widely represented in nature and used for the synthesis of biologically active substances. Among the 1,3-thiazine derivatives, promising compounds as antimicrobial and antiviral drugs

• (PD404182) [1][2][3][4], sedative [5] and antitumor agents [6][7][8], as well as fungicides [9][10] and insecticides [11] have been found (Figure 1). The 1,3-thiazine heterocyclic system is comprised in some natural phytoalexins (cyclobrassinin, sinalbins A and B, rutalexin, and others) [12] and 7

• -aminocephalosporanic acid (7-ACA), which is a key fragment of broad-spectrum cephalosporin antibiotics [13][14]. Condensed 1,2,4-triazines attract attention of researchers due to their diverse biological activities [15] and also their application as starting materials for the constructing of new heterocyclic systems

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• ]pyridines represent an important class of heterocyclic compounds, which skeleton is the key frame of many bioactive and natural compounds. For example, tetrahydrofuro[3,2-c]pyridine A demonstrates excellent in vitro JAK2 inhibitory activity superior to tofacitinib (Figure 1) [1]. Furan B is a potent κ

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• as one of the most valuable synthons to construct diverse carbocyclic and heterocyclic systems as well as many open-chain compounds [9][10][11][12][13][14][15]. In recent years, in situ generated Huisgen 1,4-dipoles were also widely employed to design highly efficient multicomponent and domino

• reactions [16][17][18][19][20][21][22][23][24][25]. Recently, much attention has been devoted to the development of new domino reactions containing reactive Huisgen 1,4-dipoles as key components for the assembly of many biologically important nitrogen-containing six-membered heterocyclic compounds [26][27

• behaved as an activated electron-rich dienophile. Inspired by these elegant synthetic methodologies and in continuation of our aim to develop well-known Huisgen 1,4-dipoles for the construction of diverse nitrogen-containing heterocyclic compounds [45][46][47][48][49][50][51][52][53][54][55][56][57][58

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• acyclic, carbocyclic, heterocyclic, and polycyclic molecular architectures with high molecular complexity. In particular, asymmetric organocatalysis plays a pivotal role in the construction of optically active, bioactive, and natural products. The main advantages of organocatalyzed stereoselective

• the reaction partners in a highly ordered three dimensional transition state through noncovalent interactions (like H-bonding, π–π interactions) thus promoting the stereoselective reaction. Examples of covalent bonding organocatalysts are amines [6][7], N-heterocyclic carbenes [8][9], phosphines [10

• products 23 framed with an aza-quaternary stereocenter. Indole derivatives without any substitution in the heterocyclic ring participated in the reaction through the C3 position smoothly providing the products with appreciable yields and enantiocontrol. Two examples were demonstrated with 3-alkyl

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• is an important aromatic heterocyclic scaffold found in many natural products and predominantly used in pharmaceuticals. Continuous efforts are being made to design and synthesize various pyrrole derivatives using different synthetic procedures. Among them, the Clauson–Kaas reaction is a very old and

• -dimethoxytetrahydrofuran; green synthesis; microwave-assisted reaction; N-substituted pyrrole; Introduction Heterocyclic compounds are the most explored molecules in organic chemistry in terms of their synthesis and various applications. Among the diverse heterocyclic compounds, N-containing heterocycles are found in

• many natural products [1][2][3] and biologically active molecules [4][5][6][7]. Pyrroles are a significant class of five-membered aromatic nitrogen-containing heterocyclic skeletons that have attracted much attention due to their broad spectrum of biological activity, such as anticancer [8][9][10

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• , National Institute of Pharmaceutical Education and Research - Ahmedabad, Gandhinagar, Gujarat, 382355, India 10.3762/bjoc.19.62 Abstract Pyridine is a crucial heterocyclic scaffold that is widely found in organic chemistry, medicines, natural products, and functional materials. In spite of the discovery

• ][43][44][45]. On the other hand, a metal-catalyzed functionalization of arene/heteroarene C–H bonds to the corresponding C–C bonds is an area of great interest and has been well studied [46][47]. Pyridine, being an important heterocyclic scaffold, various studies have been conducted for the C(sp2)–H

• with a bulky N-heterocyclic carbene ligand and (2,6-t-Bu2-4-Me-C6H2O)2AlMe (MAD) as the Lewis acid which allowed the direct C-4 alkylation of pyridines 1 (Scheme 12a). With the optimized reaction conditions in hand the group also screened the alkene and pyridine substrate scope which resulted C4

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• synthesis of quinoline-3-sulfonyl chlorides which are the most common reagents for their preparation. As a possible solution, the approach to the heterocyclic core construction from a sulfonamide-containing building block may be considered. In turn, diversely substituted quinoline-3-sulfones are available

• leading to 2-alkoxyquinolines. Compounds 5l an 5q were obtained in 63 and 51% yield, respectively (Scheme 3). It is worth noticing that chromenopyridine-3-sulfonamide 5h derived from heterocyclic azidoaldehyde 1h was also successfully synthesized following the methodology designed. Some limitations on the

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• important role in modern chemistry allowing to create novel original synthetic methods. UV-initiated reactions of heterocyclic systems are a significant part of organic photochemistry and there are numerous such transformations for various classes of heterocycles known in the literature [11][12][13][14][15

• the 6π-electrocyclization leading to polyaromatic products. Therefore, it is complicate to predict the photochemical behavior of terarylenes containing a 3-hydroxypyran-4-one unit. It should be noted that all the products considered above were constructed on the basis of five-membered heterocyclic

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• . Taking into account all these facts, we solved the task of developing a new approach for the synthesis of hybrid molecules containing substituted pharmacophoric heterocyclic and peptidomimetic fragments. An approach based on the preparation of an imidazo[1,2-a]pyridine-containing heterocyclic acid and

• 24 hours at room temperature in DMF with catalytic amounts of HClO4. The yield of compound 4a in this case was 76%. Then new heterocyclic acids were used as reagents for the Ugi four-component reaction. Due to the rather low solubility of the acids in methanol, it was necessary to increase the

• temperature and the reaction time. After a series of experiments, it was found that stirring the isocyanides 3a–d, heterocyclic acids 4a–c, aldehydes 5a–e, and primary amines 6a–d at 50 °C in methanol for 24–48 hours (depending on the nature of the starting materials) allowed obtaining the Ugi target products

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• an oxygen in the heterocyclic ring as opposed to nitrogen in azepines, are known from natural sources (compounds 13–18 as examples) [17][18][19][20][21][22][23][24][25], the application thereof in a clinical setting is limited (Figure 5). Novartis CGP 3466 (19), a propargylamine derivative, showed

• heteroatoms (e.g., O, N, S, P, B and Si) in the heterocyclic ring result in analogues of dibenzo[b,f]azepines and -oxepines. This group of compounds will thus be broadly referred to as dibenzo[b,f]heteropines (1). The first section of this review will cover the synthesis of dibenzo[b,f]heteropines (1) and

• etherification entails the palladium or copper-catalysed formation of a carbon–heteroatom bond. Despite significant successes and facile access to the core tricyclic motif, access to dibenzo[b,f]heteropines with disparately substituted aromatic rings fused to the heterocyclic ring and varied substitution

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• phosphorus-containing heterocyclic compounds [1][2] and significant agrochemicals [3], medicinal agents [4], and organic materials [5]. They are also organic synthetic intermediates and building blocks [6][7]. To date, only limited four-membered β-phostams [8][9], β-phostones and β-phostines [10] have been

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• unsaturation required the presence of two heterocyclic rings in the molecule. The presence of an ester carbonyl signal (δC 167.0) and a deshielded oxygenated carbon resonance at C-12′ (δC 104.1) implied the formation of six-membered ring via an ester bond between C-16 and C-12′. In addition, an epoxide moiety

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• targeted cancer therapy development. Keywords: 1,4-benzothiazine; 1,3-benzothiazole; 1H-pyrrole-2,3-diones; nitrogen heterocycle; sulfur heterocycle; Introduction Pyrrolo[2,1-b][1,3]benzothiazole (PBTA) is an angularly fused sulfur and nitrogen-containing heterocyclic scaffold. Its derivatives are

•  4). Results and Discussion It is known that [e]-fused 1H-pyrrole-2,3-diones (FPDs) (Figure 2) are versatile synthetic platforms enabling the synthesis of numerous heterocyclic species [33][34][35][36]. They are polyelectrophilic compounds, bearing five electrophilic centers, whose reactivity

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• of heterocyclic enolates 108 generated from coumarin and chromone [65]. The high enantio- and diastereoselectivity of these transformations were ensured by a Josiphos-type ferrocene ligand. The reaction of chiral metal enolates with onium compounds enabled the installation of structurally attractive

• , which begins with a Cu-catalyzed enantioselective conjugate addition/enolate alkylation tandem reaction sequence utilizing the N-heterocyclic carbene ligand L40 [112]. Ketone 232 was isolated in 61% yield and 81% ee. Hereafter, the authors were able to synthesize the complex tetracyclic structure within

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• were moderately soluble in DMSO (up to c = 1 × 10−3 mol dm−3) and their stock solutions were stable during a few months. All measurements were recorded in the Na cacodylate buffer (Ic = 0.05 mol dm−3) both at pH 5.0 and pH 7.0 for comparison, since the phenanthridine heterocyclic nitrogen becomes