Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• much more efficiently in decarboxylative RLT reactions than aliphatic acids [42]. Outside of decarboxylation, X. Peter Zhang recently reported the enantioselective synthesis of allylic amines through coupled HAT and RLT on allylic C–H bonds [45], using a bulky cobalt porphyrin complex developed and

• beautiful decarboxylative azidation examples, combining iron-mediated photodecarboxylation via LMCT and azide RLT (Scheme 5) [11]. Irradiating a substoichiometric amount of iron(III) nitrate hydrate III in the presence of carboxylic acid, TMS azide, and sodium carbonate allows for direct synthesis of alkyl

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• ; multicomponent synthesis; one-pot reaction; trichloroacetic acid; Introduction π-Conjugated porphyrin macrocycles are known for their applications in numerous areas ranging from oxygen transport, photosynthesis, catalysis and medicine [1][2][3]. In the past several years, diverse organic scaffolds have been

• aldehydes and dimedone in chloroform at 65 °C. The optical properties of the newly prepared porphyrins have been investigated by using UV–vis and emission spectroscopy and the results are presented in this paper. Results and Discussion Synthesis The required precursors, copper(II) 2,3-diamino-5,10,15,20

• /toluene 1:10 mixture under inert atmosphere to afford 2-amino-3-nitro-meso-tetraarylporphyrins which on reduction through sodium borohydride in the presence of 10% Pd/C in CH2Cl2/MeOH provided the desired porphyrins 1 in good yields as key starting materials for the synthesis of newly designed benzo[f

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

• photosynthesis. It is also noteworthy that the reduced pyridinium compounds resemble Hantzsch esters which are organic reductants commonly used in organic synthesis. Quinones and hydroquinones have also been used in RFBs. Notably, 1,4-hydroquinone and 1,4-benzoquinone were used to create membrane-less RFBs with

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• Valeriy O. Filimonov Alexandra I. Topchiy Vladimir G. Ilkin Tetyana V. Beryozkina Vasiliy A. Bakulev Technology of Organic Synthesis Department, Ural Federal University named after the first President of Russia B. N. Yeltsin, 19 Mira st. Yekaterinburg 620002, Russia Department of Organic Chemistry

• -enethioamides with hydrazine and its derivatives, the interaction proceeds with the participation of cyano- and enamine groups, not affecting the thiocarbamoyl group, and leads to the formation of 4-thiocarbamoylpyrazoles. A synthesis method has been developed and a series of 1-substituted-4-thiocarbamoyl

• potential of such compounds. The most common method for obtaining 3,5-disubstituted pyrazoles is the cyclocondensation of 1,3-bielectrophilic reagents with hydrazine, which acts as a 1,2-dinucleophile [15][16]. It is worthy to note that a small number of methods for the synthesis of 3,5-diaminopyrazoles are

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• reductive elimination of iodobenzene to give 11 (Figure 5, left). This was also the pathway subsequently suggested by Gallos et al. [116] for the synthesis of 13/14 from 12. In 2003, Hadjiarapoglou further investigated the intermolecular reaction between 8 and cyclopentene under thermal, metal-free

• calculations for enaminone synthesis from iodonium ylides and thioamides. Crystal structures of 76c (top) and 76e (bottom) [101], (CCDC# 2104180 & 2104181) [143][144]. Outline of possible reaction pathways between iodonium ylides and Lewis basic nucleophiles (top); and, reaction between 6 and HCl to give 7, as

• synthesis from acyclic iodonium ylide 31 and tertiary amines. N-Heterocycle synthesis from acyclic iodonium ylide 31 and secondary amines. Indoline synthesis from acyclic iodonium ylides 39 and tertiary

Retraction: One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2023, 19, 1170–1170, doi:10.3762/bjoc.19.85

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• Ave., 55a, 644077 Omsk, Russian Federation 10.3762/bjoc.19.83 Abstract An effective one-pot strategy was developed for the synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones from pyrazolo[3,4-b]pyridin-6-ones, obtained by reacting 5-aminopyrazoles with 4-arylidene-2-phenyloxazol-5(4H)-ones (azlactones

• when irradiated with UV light. Keywords: 5-aminopyrazole; azlactone; elimination; fluorescence; one-pot synthesis; pyrazolo[3,4-b]pyridin-6-one; Introduction The pyrazolo[3,4-b]pyridine scaffold is present in many biologically active compounds [1][2][3][4][5][6][7][8][9][10][11][12]. Among them, 4

• -aryl-substituted derivatives should be distinguished, exhibiting antiviral [13] and anti-inflammatory properties [14], being modulators of estrogen-related receptor alpha [15], JAK1 kinase inhibitor [16], GSK3 [17] and GyrB [8] inhibitors (Figure 1). Despite the high demand, their synthesis methods are

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• synthesis [17][18][19][20], although they are less commonly utilized than the other two functional groups. Over time, various synthetic protocols for oxygenation reactions have evolved. Initially, stoichiometric amounts of toxic oxidants were used, but now more sustainable oxidants such as H2O2 [21][22], O2

• ) significantly slowed down the reaction. Gratifyingly, we observed excellent selectivity for substrates that contained an additional sulfur atom in the structure. Thus, thianthrene selectively generated product 2c, which is an important precursor for the synthesis of thianthrene salts [37]. To our delight, the

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

• radicals that often provide access to new dimensions of synthetic chemical space, the field of single electron transfer (SET) in organic synthesis has expanded considerably in the past two decades. Among this area, photoredox catalysis (PRC) is highly attractive due to its abilities i) to generate reactive

• first efforts in this direction [32][33]. Finally, both techniques are amenable to large-scale synthesis and ideally integrated with state-of-the-art reactor technology platforms, such as continuous flow reactors and high throughput screening plates. Various examples of scalability will be highlighted

• in this Review, with a particular emphasis on the challenges and areas for improvement, such as the standardization of reactors capable to conjugate applied potential and light irradiation either in different modules or within the same flow path. 2 conPET in organic synthesis 2.1 Reductive activation

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

• [16][17]. Recent studies of the antitumor activity of imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazines revealed a number of compounds with a high antiproliferative effect towards a large number of human cancer cell lines (Figure 1) [18][19]. Therefore, the synthesis of new imidazothiazolotriazines and

• heterocyclic system, namely imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines 3 (Scheme 1B). Results and Discussion In a continuation of our studies [22] aimed at the synthesis of functionalized imidazothiazolotriazine derivatives, we attempted to hydrolyze the ester group of imidazothiazolotriazines 1 and to

The effect of dark states on the intersystem crossing and thermally activated delayed fluorescence of naphthalimide-phenothiazine dyads

• Liyuan Cao,
• Xi Liu,
• Xue Zhang,
• Jianzhang Zhao,
• Fabiao Yu and
• Yan Wan

Beilstein J. Org. Chem. 2023, 19, 1028–1046, doi:10.3762/bjoc.19.79

• . Experimental General methods All the chemicals used in synthesis are analytical pure and were used as received without further purification. UV–vis absorption spectra were measured on a UV-2550 Shimadzu spectrophotometer. Fluorescence spectra were recorded with an FS5 spectrofluorometer (Edinburgh instruments

• ., U.K.). NI-PTZ-F, NI-PTZ-Ph, NI-PTZ-CH3, NI-PTZ-OCH3, and the oxidized molecules NI-PTZ-F-O were prepared according to the literature methods [11][39][43][71]. Synthesis of NI-PTZ-F Compound NI-PTZ-F was synthesized by a modified literature method [39]. Under N2 atmosphere, F-NI-Br (200 mg, 0.542 mmol

• . Synthesis of NI-PTZ-Ph NI-PTZ-Ph was synthesized by a reported method [11][71] similar to that of NI-PTZ-F. The crude product was purified by column chromatography (silica gel, DCM/PE 1:3, v:v). Compound NI-PTZ-Ph was obtained as orange solid. Yield: 243 mg (52%); mp 126.2–127.2 °C; 1H NMR (CDCl3, 400 MHz

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• purification steps. Keywords: automated glycan assembly; photocleavable linker; polysaccharides; solid-phase synthesis; Introduction Automated glycan assembly (AGA) is a solid-phase method that enables the rapid synthesis of complex oligo- and polysaccharides from protected monosaccharide building blocks

• mostly performed on cross-linked polystyrene resins equipped with photocleavable linkers [3], offering orthogonality to all the synthetic steps of the assembly, while selectively releasing the glycan at the end of the synthesis. In recent years, the implementation of new synthetic strategies [4][5][6][7

• scale [19], and linkers [20][21] affect the overall yield of solid phase peptide synthesis (SPPS). In the past decades, several supports and linkers have been developed and commercialized for SPPS, enabling a wide range of applications. Solid supports are available with different linker loadings, with

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• anti-inflammatory agent (Figure 1). Owing the importance of arylamines and their biological significance, the surge of development of innovative methods for their synthesis has been always an area of interest [12]. Specifically, the metal-mediated arylation reactions have witnessed significant

• halogenated solvents. Moreover, the use of economic and eco-friendly solvents such as water have always been an attractive area in organic synthesis. Therefore, in continuation of our efforts towards the development of sustainable methods for the synthesis of valuable organic molecules, herein, we report a

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

• Elena Y. Mendogralo Maxim G. Uchuskin Perm State University, Bukireva st. 15, Perm, 614990, Russian Federation 10.3762/bjoc.19.74 Abstract A semi-one-pot method for the synthesis of 4-substituted tetrahydrofuro[3,2-c]pyridines by the Pictet–Spengler reaction was developed. The method is based on

• relatively selective α2-adrenoceptor antagonist [5]. Despite the simplicity of the tetrahydrofuro[3,2-c]pyridine core, only limited approaches for the synthesis of this subclass of heterocycles using furan derivatives as starting compounds have been described [6][7][8]. The first group of methods is based on

• -c]pyridines. Moreover, multistep cascade processes with the simultaneous construction of several cores were described, where the key step is the generation of an acyliminium cation and the Pictet–Spengler cyclization [30][31][32], including solid-phase synthesis [33][34][35]. Another route for the

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

• -fused tetrahydroquinolines (reaction 1 in Scheme 1) [41][42]. Menéndez and co-workers reported a Yb(OTf)3-mediated Povarov reaction of imines and N-alkyl-1,4-dihydropyridines for the synthesis of hexahydrobenzo[h][1,6]naphthyridines (reaction 2 in Scheme 1) [43]. Khan and co-workers employed a one-pot

• ][59][60][61][62][63][64], herein, we wish to report the use of 5,6-unsubstituted 1,4-dihydropyridines as electron-deficient alkenes in the Huisgen 1,4-diploar cycloaddition and as electron-rich alkenes in formal [2 + 2] cycloadditions for the efficient synthesis of isoquinolino[1,2-f][1,6

• an intramolecular Michael addition process. Conclusion In summary, we have investigated the three-component reaction of isoquinoline, dialkyl acetylenedicarboxylate and 5,6-unsubstituted 1,4-dihydropyridines. This reaction successfully provided an efficient protocol for the synthesis of

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

• years ago, the concept became increasingly accepted and popular only by the last decade of the last century [2][3]. Nowadays, organocatalysis is especially applied to asymmetric synthesis and a huge number of organocatalysts has been introduced in last three decades for the asymmetric synthesis of

• -substituted indoles which effectively attacked the electrophile through the C2 position. The reaction was even compatible with pyrroles (Scheme 7a). The utility of this methodology was successfully demonstrated by the synthesis of product 23a, the key intermediate of natural product (+)-trigonoliimine (Scheme

• substitutents. Excellent dia- and enantioselective synthesis of the products were caused by a chiral environment induced in the transition state through a dual H-bonding interaction between both the substrates and catalyst. In addition, π–π stacking between the aromatic moieties in both reagents brought more

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

• compounds. As a result, this review describes the use of various eco-friendly greener protocols to synthesize N-substituted pyrroles. This synthesis involves the reaction of various aliphatic/aromatic primary amines, and sulfonyl primary amines with 2,5-dimethoxytetrahydrofuran in the presence of numerous

• acid catalysts and transition metal catalysts. The goal of this review is to summarize the synthesis of various N-substituted pyrrole derivatives using a modified Clauson–Kaas reaction under diverse conventional and greener reaction conditions. Keywords: catalyst; Clauson–Kaas pyrrole synthesis; 2,5

• -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

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• accomplish by more conventional procedures, enables the synthesis of ergot alkaloid precursors. In addition, this work describes a mild, environmentally friendly method to activate, reductively and oxidatively, natural carboxylic acids for decarboxylative C–C bond formation by exploiting the same

• photocatalyst. Keywords: decarboxylative cyclization; DMAT; ergot alkaloids; photoredox catalysis; radicals; Introduction Visible-light photoredox catalysis is rapidly changing the way organic chemists approach the design and synthesis of molecules by offering new synthetic disconnection opportunities that

• ground state catalyst [21][22][23][24][25][26]. While early research has focused on methods for the functionalization of relatively simple hydrocarbons [27][28][29][30], developments in photoredox catalysis have gained traction recently as a viable strategy for the total synthesis of natural products [31

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• thiazole or thiazoline substituent, compounds 2–6 have not been reported before according to literature searches. Compound 1 was already described as an intermediate in the chemical total synthesis of micacocidin [35], but has not been isolated from a natural source before. Conclusion In summary, six

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• the construction of a range of δ-olefin-containing aliphatic nitriles with (E)-configuration selectivity. This new method features wide substrate scope, mild conditions, and direct N–O activation. Keywords: direct N–O activation; E-selectivity; nitrile synthesis; ring-opening cross-coupling; sulfuryl

• of novel synthetic methods and strategies toward nitrile group construction continues to be a focus for synthetic chemists. The cross-coupling reactions of C–C bonds catalyzed by transition-metal complexes play a crucial role in modern organic synthesis, as they make it feasible to synthesize complex

• structures from available components [11][12][13]. Indeed, the formation of C(sp2)–C(sp3) bonds by cross-coupling has developed rapidly in recent years [14][15][16], but it still remains less advanced than the synthesis of C(sp2)–C(sp2) bonds [17][18]. This is attributed to the electron-richness of the C(sp3

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• ). These structural features enable the construction of a five-membered ring upon treatment with alkenes [9], diazo compounds (reaction g) [10], and nitriles [11]. Several approaches are available for the synthesis of cyclopropanedicarboxylates 1a, which consist of three steps: 1) conjugate addition, 2

• 3b used in only three cases [12][13][19], to the best of our knowledge. Extending beyond Scheme 2, only two syntheses of nitrocyclopropanes containing cyclic keto esters or diketones have been reported [20][21]. These findings indicate that the synthesis of nitrocyclopropanes with an acyl group is

• quite difficult, although they would be very useful in synthetic chemistry, if available. In this study, we investigated the synthesis of nitrocyclopropanes using keto esters 3c–f and diketones 3b and 3g instead of diester 3a as the starting 1,3-dicarbonyl compounds. Results and Discussion We commenced

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• its applications in the total syntheses of complex natural products and other molecules of biological relevance [13][14]. Acylimidazoles proved to be versatile building blocks broadly applicable in asymmetric catalysis and organic synthesis. Today, acylimidazoles are used as ester/amide surrogates

• , because of their particular chemical and physical properties [15]. In addition to ester/amide synthesis, enoyl imidazolides were developed as excellent Michael acceptors. Acylimidazoles are unique electrophiles that demonstrate moderate reactivity, relatively high stability, chemical selectivity, and high

• solubility in water. Among exceptional properties belongs to easy post-transformation of acylimidazoles to common carbonyl analogs. These tunable properties allow the use of acylimidazoles in chemical biology research, which includes chemical synthesis of proteins/peptides, structure analysis, and functional

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

• of several methods for the synthesis of functionalized pyridines or their integration into an organic molecule, new methodologies for the direct functionalization of pyridine scaffolds have been developed during the past two decades. In addition, transition-metal-catalyzed C–H functionalization and

• materials [1][2][3][4][5][6][7][8][9][10]. Due to its different characteristics such as basicity, stability, water solubility, small molecular size, and ability to form hydrogen bonds, pyridine continues to be a suitable moiety in organic synthesis. In addition, it has been observed that pyridine rings

• serve as bioisostere for aromatic rings, amines, amides, and N-containing heterocycles. Due to the aforementioned qualities, numerous U.S. FDA-approved medications have pyridine scaffolds in their molecules (Figure 1). In this context, the synthesis of the pyridine motif is always there in trend. Many

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• thiazole synthesis and elimination to nitriles) were identified. The key factor that enables the successful Eschenmoser coupling reaction involves the optimum balance in acidity of nitrogen and carbon atoms of the intermediary α-thioiminium salts. Keywords: Eschenmoser coupling reaction; Hantzsch thiazole

• synthesis; isoquinolin-4-ones; primary thioamides; structure–reactivity relationships; Introduction During several past years, we have developed [1][2] a novel synthetic approach toward (Z)-3-[amino(phenyl/methyl)methylidene]-1,3-dihydro-2H-indol-2-ones and have demonstrated [3][4] its application

• potential in the synthesis of various tyrosine kinase inhibitors, including hesperadin and the approved drug nintedanib. The key step of the synthesis involves the Eschenmoser coupling reaction (ECR) between a substituted 3-bromooxindole 1 and appropriate primary, secondary or tertiary thioamides which

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

• have developed a new convenient protocol for the synthesis of 3-sulfonyl-substituted quinolines (sulfonamides and sulfones). The approach is based on a Knoevenagel condensation/aza-Wittig reaction cascade involving o-azidobenzaldehydes and ketosulfonamides or ketosulfones as key building blocks. The

• 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

• . While the ortho-amino carbonyl reagents are not always easily accessible and sometimes unstable (e.g., aminoaldehydes), both o-azidoaldehydes [58][59][60][61][62][63][64][65] and o-azidoketones [66][67][68][69] have been proved to be appropriate substrates for quinoline derivatives synthesis. Recently