Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• were tolerated, while a dioxazolone containing bromobenzene displayed lower reactivity (26c). The enamide 26d, derived from lobatamide, was successfully produced without altering the stereochemistry of the oxime ether. Terminal alkynes with linear alkyl group, protected alcohol, and sulfonamide

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• either debenzylated and subsequently transformed into a thiourea organocatalyst or turned into an axially chiral sulfonamide. In 2022, Yang et al. presented their (3 + 2) formal cycloaddition of alkynylindoles 184 with azonaphthalenes 185 catalyzed by the SPINOL-based CPA C26 (Scheme 54) [82]. The

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• . A plausible mechanism is proposed, suggesting a possible radical pathway. Keywords: electrophilic amination; hypervalent iodine reagents; sulfinamide; sulfonamide; Introduction Iodine(III) compounds, known as λ3-iodanes, have been extensively applied in organic synthesis. Although initially used

• reactivity with in situ-generated sulfenate anions, from β-sulfinyl esters, to achieve S–N bond formation. The importance of establishing this S–N bond results from the widespread presence of sulfonyl-containing bioactive compounds, such as the sulfonamide group which can be found in many pharmaceuticals

• , commonly referred to as sulfa drugs. These include top seller drugs, e.g., antimicrobials, anti-inflammatories, antihypertensives, and antitumor agents [24][25][26]. Particularly, the sulfonamide motif can act as a bioisostere of carboxylic acids, establishing a set of hydrogen bonds similar to those

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• cyclic derivatives. Conjugated imines are usually synthesized from the corresponding carbonyl precursors by reaction with a sulfonamide in the presence of Lewis acids and a dehydrating agent such as molecular sieves [3]. Also, recently a palladium-catalyzed dehydrogenation of aliphatic imines was

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• , an intramolecular cyclization takes place, facilitated by CuI. This step involves a 5-endo-dig cyclization, where the negatively nitrogen atom of the sulfonamide 25 attacks intramolecularly to yield the intermediate 26. The final product is formed when iodide is regenerated as CuI, allowing it to re

• -enter into the catalytic cycle. On the other hand, the sulfonyl group in its sulfonamide form is typically associated with antibacterial activity. However, it has been little studied the sulfonyl group regarding biological activity when attached to the indole nitrogen. Although scarce, some recent

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• cation is formed by oxidation of the substrate at the anode. This radical cation is subsequently deprotonated to produce an allyl radical. The allyl radical is further oxidized to form the allyl cation, which is then attacked by the nucleophilic sulfonamide, leading to the formation of the desired C–N

• protocol for the installation of sulfonamide groups using commercially available SO2 and amines (Scheme 12) [20]. This method is highly appealing for industrial applications and LSF. The proposed mechanism begins with the anodic oxidation of the arene substrate. The resulting radical cation intermediate is

• then attacked by the nucleophilic amidosulfinate, which also functions as an electrolyte. The amidosulfinate is generated through the formation of a Lewis acid–base adduct. A subsequent oxidation step, accompanied by deprotonation, yields the sulfonamide product. SO2 captures the excess electrons via

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• by extended reaction times, sometimes up to 168 hours. An intriguing example involves the use of a bifunctional primary amine-sulfonamide catalyst, which activates benzylideneacetone towards dibenzyl malonate, with the presence of water accelerating the reaction [25]. An alternative approach, where

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• selected as it underwent efficient aziridination with PhINTs. A family of iminoiodinanes 2 was synthesized from PIDA and the corresponding sulfonamide derivative. Reaction of phenylsulfonamide-derived iminoiodinane with cyclopentene afforded N-phenylsulfonylaziridine 6b in 45% yield, while N-(p

• with the stability of the relevant iminoiodinane reagent, with higher yields attributed to more electron-rich sulfonamide substitution such as 2a. Relatively electron-deficient iminoiodinanes are less efficient but are also more prone to decomposition (see Supporting Information File 1, Figure S2 for

• of the sulfonamide resulted in O–H proton signal of HFIP being at 5.64 ppm with FWHM = 11.3 Hz. Second, to evaluate the impact of HFIP on the redox chemistry of PhINTs, we collected cyclic voltammograms (CVs) of iminoiodinane 2c in MeCN in the presence of varying HFIP increments (Scheme 4b). The CV

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• organocatalyst was demonstrated by List and co-workers, who showcased the robustness of a cinchona alkaloid-based sulfonamide organotextile catalyst 36 (immobilised on nylon 6,6) through hundreds of recycling experiments (Scheme 11) [15]. The organotextile catalyst 36 exhibited a very similar enantioselectivity

• asymmetric Michael addition of pentane-2,4-dione (32) and trans-β-nitrostyrene (11). Alcoholytic desymmetrisation of a cyclic anhydride 34 catalysed by polyamide-supported cinchona sulfonamide 36. Funding This research was funded by the National Research, Development, and Innovation Office (grant number

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• aza-Wacker cyclizations under acidic conditions, which are expected to proceed via radical cations generated by single-electron oxidation of alkenes. Keywords: alkene; aza-Wacker cyclization; electrochemistry; radical cation; sulfonamide; Introduction Activating bench-stable substrates is the first

• compatible to give the respective five-membered pyrrolidines, except for that possessing a 2-nitro group 7. As discussed later with cyclic voltammetric studies, the electron density in the aryl rings does not seem to have a significant impact on the reaction. While benzyl sulfonamide 8 was productive under

• -electron oxidation of the alkenes. Although a drop in oxidation potential for the alkene was observed when tethered to an aryl sulfonamide, as detailed by Moeller, rapid intramolecular cyclization would be the key [26][27][28]. We also measured cyclic voltammograms for aryl sulfonamides with and without

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• activities of this supramolecular complex (Scheme 5), with positive in vitro activities in 20S proteasome core particles isolated from rabbit erythrocytes [28]. The sulfonamide 30 (Scheme 6) has been evaluated as inhibitor of human carbonic anhydrase I/II (hCA I and II), which catalyze the reversible

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• amines 136a–e and 138 showed better 17β-HSD3 inhibition at 0.1 µM than the secondary ones 134a–e, with some of them presenting better inhibition values than the reference compounds (RM-532-105 and D-5-2). However, only morpholinones 138 that bear sulfonamide and carboxamide groups did not exhibit

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• optimized with 5 mol % of Mn1 and 10 mol % of K2CO3 in xylene at high temperature (150 °C) for 24 h afforded the desired N-alkylated sulfonamide compounds [40]. A wide range of aryl and alkyl sulfonamides were alkylated with various benzylic and aliphatic alcohols, providing good to excellent yields (Scheme

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• particularly underinvestigated [2][18][19]. In this work we report the preparation of a new L-shaped NHC motif, the 3-aminoimidazo[5,1-b]oxazol-5-ylidene A (shortened hereafter to AImOx), which fuses two π-rich rings and positions a sulfonamide group alongside the metal centre (Figure 1b). We envisaged that

• the C(oxazole)–N(sulfonamide) bond. No coalescence is observed at up to 110 °C indicating that these motifs might be useful as a robust atropisomeric system. The molecular structure of 13 and 14 have been unambiguously determined by single crystal X-ray diffraction (Scheme 2) [28]. The N–metal

• interatomic distances are between 3.53 and 3.66 Å leaving insufficient space for bond rotation about the C–N axis with the sulfonamide substituents being approximately perpendicular to the fused aromatic unit. A percentage buried volume of 44.6% was calculated from the crystal structure of 13 using Cavallo’s

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• % conversion after 24 h, estimated t1/2 = 96 h, kobs = 1.4 × 10−6 s−1). With 55 μL MeOH in DCM, the relative rates for each substrate are 3,850:50:1 with urea 1a > carbamate 1b > benzamide 1c. The analogous toluene sulfonamide substrate 1d did not react on measurable timescales at room temperature (no product

• with alkene but also the urea carbonyl. The Bronsted acidity of the urea would be increased by coordination to gold, and if such coordination is key to enabling reactivity, this would confirm the higher reactivity of urea 1a. The divergent behavior of sulfonamide 1d does not find an easy explanation

• ; there are similarities and differences in the way a sulfonamide or carbonyl impacts a neighboring nitrogen. Sulfonamides have different steric profiles from carbonyls [51]. According to Roush et al. the electron-withdrawing capability of the S(O2)Ph group is in between that of the C(O)Me and CO2Me

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• ) derivative (Figure S2 in Supporting Information File 1). The lower yield of 2b compared to 2a is probably due to the [2 + 2 + 2] homocoupling cycloaddition of the corresponding starting diyne, which is more favorable when the tether is a malonate rather than an NTs-sulfonamide. Among the four different [6,6

Substituent-controlled construction of A₄B₂-hexaphyrins and A₃B-porphyrins: a mechanistic evaluation

• Seda Cinar,
• Dilek Isik Tasgin and
• Canan Unaleroglu

Beilstein J. Org. Chem. 2023, 19, 1832–1840, doi:10.3762/bjoc.19.135

• negative and positive ion mode. After two minutes, tripyrrane sulfonamide II and azafulvene I mass peaks were observed. Later on, tripyrrolic intermediates III and VI predominated and the mass peak of IV was observed with poor intensity in the spectra (Figure 1 and Figure S47 in Supporting Information File

• of sulfonamide groups from pyrrolic sulfonamides [36]. Here in this work, during the reaction at 0 °C, intermediates I–VI were detected (Figure 1). The primary intermediates II and IV are formed by the addition of tripyrrane 1 to tosylimine 2d. Further elimination of N-tosyl group(s) from these

• intermediates gives azafulvene-ended secondary intermediates III, V, and VI. The observed intermediates I–VI having sulfonamide or azafulvene ends are in accordance with our previous findings [26][35][36]. In addition, the observation of azafulvene I could be attributed to the fragmentation of tripyrrane 1

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

• -(arylthio)succinimides 1 or N-(arylseleno)succinimides 1’’ was developed under a Lewis acid catalysis system. This reaction involves ring-opening of the substituted cyclopropane 49, amination at the C1-site, and thiolation at the C3-site. In the transformation, sulfonamide acted as a nucleophile

• with N-(arylthio)phthalimide 14 and N-chlorophthalimide (96) under phase-transfer conditions was developed by Maruoka and co-workers (Scheme 39) [74]. The presence of chiral bifunctional catalysts C and D with the amide, or sulfonamide moieties could improve the enantioselectivity. Also, the

• Lewis base organocatalysts (Scheme 56) [88]. In this procedure, the cyclized products were obtained via the activation of the sulfur electrophile by a Lewis base to generate the thiiranium ion intermediate from the β,γ-unsaturated sulfonyl carboxamide. The attack of the sulfonamide nitrogen atom on this

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

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

• novel quinoline construction and functionalization techniques resulting in new or rare derivatives [17][18][19][20][21][22][23][24][25][26] is an important mission in the field of drug discovery and medicinal chemistry. The sulfonamide group is a known privileged motif in drug design often serving as a

• linker or pharmacophore group. In fact, more than one hundred FDA-approved drugs are sulfonamide-bearing small molecules. Screening libraries of aromatic and heteroaromatic sulfonamides gave rise to the discovery of multiple physiologically active compounds [27][28][29][30] including important

• pharmaceuticals, such as sulfamethoxazole and sulfasalazine (Figure 1a). In this context, combining sulfonamide and quinoline fragments promises to be a fruitful strategy to identify diverse types of therapeutically relevant compounds. The effectiveness of this approach is demonstrated by a series of bioactive

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• single electron transfer (SET), is proposed to be involved in the plausible reaction mechanism. Keywords: arylsulfonylimine; benzylic oxidation; benzyl sulfonamide; K2S2O8; sulfate radical anion; Introduction Among various imine compounds [1], N-arylsulfonylimines are perhaps the most prominent due to

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• proceeded further, in uncatalyzed fashion at room temperature and yielded, after intramolecular azide–alkyne click reaction novel, structurally intriguing bistriazoles. Keywords: α-acetyl-α-diazomethane sulfonamide; intramolecular click reaction; uncatalyzed; room temperature; 1,2,3-triazoles

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• compatible means in the view of a one-pot methodology for preparing isocyanides directly from amines [56]. When the amine 1 was reacted in the presence of Et3N, HCOOH, and p-Ts-Im [58] (Table 1, entry 5), the formamide was accompanied by a significant amount of sulfonamide (formamide/sulfonamide ratio: 70:30

• . Under these experimental conditions, we did not detect the formation of the sulfonamide derivative, preserving complete selectivity towards the target formamide (Table 2, entry 4). Remarkably, the results remain unchanged regarding yields and purity by shortening the reaction time (Table 2, entry 5

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• reactivity than the sulfonamide reagents such as Barnette’s N-fluoro-N-alkylarenesulfonamides, since the electronic density on the nitrogen was greatly decreased by two strong electron-withdrawing CF3SO2 groups. Reagent 7-1a reacted slowly with benzene and toluene under neat conditions, whereas activated

• pentafluoropyridine, the precursor 11-1 was prepared as illustrated in Scheme 25. Treatment of 11-1 with neat F2 in acetonitrile at −10 °C under reduced pressure gave N-fluoro-sulfonamide 11-2 in 89% yield. This product was however a 9:1 mixture of the N-F reagent 11-2 and the protonated compound of 11-1. The

• -rich substrates such as sodium diethyl (phenyl)malonate, 1-morpholinocyclohexene, phenol, and anisole (Scheme 47). The fluorination power of the carboxamide 21-2 was less than that of its N-F sulfonamide analog 11-2. 1-22. N,N’-Difluoro-1,4-diazoniabicyclo[2.2.2]octane salts In 1996, Umemoto and co

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

• produce the corresponding triazole disulfide 98 [55]. A convenient route to triazole-fused sultams 104 was reported by Latyshev et al. It comprises a modified CuIAAC cycloaddition to produce intermediate sulfonamide-tethered 5-iodo-1,2,3-triazoles 103, followed by a base-mediated cyclization under

• )amine (TTTA) as ligand, and THF as solvent at 50 °C. The obtained sulfonamide-tethered 5-iodo-1,2,3-triazoles 103 were then cyclized upon heating in the presence of Cs2CO3 to give triazole-fused sultams 104. A good to excellent yield of sultam derivatives 104 containing aryl and alkyl substituents on