Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• cyclic amines. Next, we will examine some important derivatives of amines, such as amides and sulfonamides. Throughout, the emphasis will mostly be on bioactive molecules, but finally this section will conclude by examining a different type of molecular function, namely, organocatalysis. When fluorine is

• important derivatives of amines, namely amides and sulfonamides. Model studies with simple β-fluoroamides (e.g., 106 and 107, Figure 12) reveal that such molecules consistently adopt conformations in which the F–C–C–N dihedral angle is gauche [183][184][185]. This situation is reminiscent of that already

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• facilitated the cyclization, and the 6-membered heterocycles 6h,i could be obtained in 27% and 18% yield, respectively. In addition to sulfonamides, carbamates such as N-Boc and benzamide are also suitable as nucleophiles for the anodic decarboxylation/cyclization reaction. However, the corresponding 2

• tethered nitrogen nucleophiles such as sulfonamides, carbamates, and benzamide. The decarboxylative cyclization of a stereogenic center-containing sulfonamide proceeds with excellent diastereoselectivity (97:3 dr). The N-protected 2-aminoproline derivatives can be incorporated into dipeptides by an ester

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• directly to the alkene, then reacts with the nucleophile to afford product 7. The regioselective 1,2-difunctionalization of allyl alcohol has been developed as a three-component cascade reaction using arenes and sulfonamides as nucleophiles to achieve arylation/hydroamination processes. The reaction

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

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

• reagents (HIRs) bearing a benzylamine with in situ-generated sulfenate salts was investigated. Under the studied conditions sulfonamides have been obtained in up to 52% yield. This reaction has been extended to a variety of HIRs and sulfenate salts to explore the different reactivity of these new reagents

• a central theme of the work carried out by our research group in recent years, focusing on the formation of the S–N bond by applying the umpolung reactivity of HIRs, in particular in the preparation of sulfonamides and sulfonyl hydrazides [22][23]. In both approaches, a sulfonyl-containing

• electrophilic amination reaction afforded sulfonamides 5aa, 5ba, 5da, and 5ea with moderate yields. However, no amination product was detected with tert-butyl 3-(benzylsulfinyl)propanoate (4c). This result suggests that aliphatic β-sulfinyl esters may not possess sufficient nucleophilicity to react with the

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• functional groups and avoids the use of highly toxic and corrosive bromine. Approaches using this approach are outlined below. Nitrogen nucleophiles In 2007, aminobromocyclisation of homoallylic sulfonamides 53 was reported by Fan, Wang and co-workers (Scheme 29) [50]. Using PhI(OAc)2 as an oxidant with KBr

• as the bromine source and Bu4NBr as a reaction promoter, racemic brominated pyrrolidines 54 were synthesised from a range of homoallylic sulfonamides 53 in excellent yields under mild conditions at room temperature. A mechanism was suggested by the authors (Scheme 29), whereby ligand exchange on PhI

• . Proposed mechanism for the synthesis of chloromethyl oxazolines 49. Oxychlorination to form oxazine and oxazoline heterocycles promoted by BCl3. Aminobromocyclisation of homoallylic sulfonamides 53. The cis:trans ratios based on the 1H NMR of the corresponding products are given in parentheses. Synthesis

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• product yield increased [93]. Similarly, the arylation of sulfonamides can also be achieved by using t-BuONa in toluene for an hour at room temperature in the presence of air (conditions D) [94]. The mechanism of the reaction involves formation of anionic intermediates I and II by the action of the base

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

• significant potential for further industrial and medicinal chemistry applications (Scheme 5). Furthermore, Ackermann and coworkers described a straightforward C(sp3)–H amination of 1,3-diarylpropenes with sulfonamides via direct oxidation of allylic C(sp3)–H bonds [13]. During the reaction process, a radical

• -bond product. To demonstrate the mildness of the LSF reaction conditions, celecoxib and topiramate sulfonamides were easily functionalized with 1,3-diarylpropene in moderate yields (Scheme 6). C–H bond oxygenation: In addition to electrochemical C–H aminations, C–H oxygenations have also been reported

• leads to an intermediate product, which is then deprotonated, generating the thiol radical. This allowed for the preparation of the para-thiolation product (Scheme 11). Sulfonamides are an important class of bioactive molecules. In 2021, the Waldvogel group disclosed the first C(sp2)–H functionalization

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

• give five-membered pyrrolidine 2, while the six-membered piperidine 3 is formed through ionic cyclization under non-electrochemical conditions. With the optimized conditions in hand, the scope of the electrochemical aza-Wacker cyclization was investigated (Scheme 3). Various aryl sulfonamides 4–6 were

• tetrasubstituted alkene 14. Cyclic voltammetric studies have provided further mechanistic insights into electrochemical aza-Wacker cyclizations. As reported by Yoon, a trisubstituted alkene is oxidized at significantly lower potential than aryl sulfonamides, suggesting that the reactions were initiated by single

• -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

• hydration reaction of carbon dioxide to bicarbonate, cyanates to carbamic acids, aldehydes to gem-diols, etc., and represent a potential therapeutic target for diseases like osteoporosis, edema, obesity or cancer [29]. Alım et al. [30] evaluated a series of thiophene sulfonamides based on the high stability

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

• homogeneous nature of the catalytic system. The mechanistic investigation suggested that the reaction proceeds via a dehydrogenative pathway confirmed by forming an aldehyde product and H2 gas which was detected by GC. In 2019, Morrill’s group reported the N-alkylation of sulfonamides using Mn1. The reaction

• 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

•  10). However, sulfonamides with electron-withdrawing groups attached to the aromatic ring (e.g., 4-NO2, 4-CN) were found incompatible with the conditions. Ke and co-workers described an exciting example of a phosphine-free Mn(I)-NHC catalyst for the N-alkylation of amines with alcohols at room

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• acid, trifluoroborate moiety, trifluoromethanesulfonate, aryl sulfonamides, and heterocycles, have been incorporated into the ortho-position of diaryliodonium structures [16][17][18][19][20][21]. Ortho-trimethylsilyl or boronic acid-substituted diaryliodonium salts can serve as aryne precursors. Ortho

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

• with up to 10 mol % JPhosAu(NCCH3)SbF6 in CD2Cl2 after 48 hours with and without added CH3OH) despite common use of sulfonamides in alkene hydroamination reports, albeit at higher temperatures. Based on our ligand survey above, we proposed to improve rates of cyclization with slower reacting substrates

• ; 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

• groups as measured by rates of Michael addition [52]. This suggests that in fact nitrogen nucleophilicity alone is not the most relevant factor since sulfonamides react much slower in hydroamination. Sulfonamide N–H bonds are significantly more acidic than urea, amide and carbamate N–H bonds (16.1 versus

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• through concerted or stepwise mechanisms. An enantioselective palladium-catalyzed three-component reaction of glyoxylic acid, sulfonamides, and aryltrifluoroborates toward synthetically useful α-arylglycine compounds is described by the Manolikakes group [11]. Moreover, Šebesta and co-workers report a

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• under the reaction conditions and afforded the bromination products 3ua and 3va in 93 and 98% yield. Finally, some other acyl motifs were investigated (3wa–za) and the results showed that the protocol could be successfully applied to sulfonamides, albeit giving the target product 3za in only 53% yield

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

•  1). In our previous works, we have shown that the reaction of pyrrole with N-tosylimines leads to pyrrole sulfonamides as the main products [35]. In another work, in the synthesis of dipyrromethane structures, we have proven the formation of azafulvene intermediates by Cu(OTf)2-appended elimination

• 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

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

• important factors, and the commonly utilized chemicals include thiols [16][17][18], disulfides [19][20][21][22], sulfenyl halides [23][24][25], sulfonamides [26], sulfenate esters [27][28], and methyl(bismethylthio)sulfonium salts [29][30]. Among various organic molecules, aryl sulfides are recognized as

• chlorinated product 21 was detected, which with POCl3 gave the cyclized product 22. Also, the synthesis of benzo[b]thieno[2,3-c]quinolone 24 as an anticancer molecule was demonstrated in this approach (Scheme 13). An intermolecular sulfenoamination of alkenes 9 with sulfonamides 25 as the nitrogen source and

• N-thiosuccinimides 1 as the sulfur source was reported by Gao and Liu et al. (Scheme 14) [52]. Highly regio- and diastereoselective β-sulfonylamino sulfides 26 were obtained from alkenes 9, N-thiosuccinimides 1, and sulfonamides 25 in the presence of 20 mol % BF3·Et2O. While the transformation in

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

• (P2O5) as a catalyst for the conversion of various aliphatic amines, aromatic amines, sulfonamides and primary amides into N-substituted pyrroles (Scheme 5). These pyrroles were synthesized in 46–100% yields by the modified Clauson–Kaas reaction between amines 10 and 2,5-DMTHF (2) in the presence of

• their expectation thus, they synthesized 13 derivatives of pyrroles in good yields in short reaction times (10–45 min). It has been observed that aromatic amines and amides take a longer time compared to the primary amines and sulfonamides. In another study, Rochais et al. [59] reported in 2004 the

• Clauson–Kaas reaction in a successive cyclization/annulation process from commercially available sulfonamides 14 in the presence of trifluomethanesulfonic acid (TfOH) as Brønsted-acid catalyst. This procedure produces only N-substituted products and preserves other positions open for further

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

• Ksenia Malkova Andrey Bubyrev Stanislav Kalinin Dmitry Dar'in Saint Petersburg State University, Saint Petersburg 199034, Russian Federation 10.3762/bjoc.19.60 Abstract Quinoline-based sulfonyl derivatives, and especially sulfonamides, are relevant and promising structures for drug design. We

• 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

• protocol is appropriate for both ketosulfonyl reagents and α-sulfonyl-substituted alkyl acetates providing the target quinoline derivatives in good to excellent yields. Keywords: aza-Wittig reaction; azides; cyclocondensation; quinolones; sulfonamides; Introduction The quinoline scaffold has a wide

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

• condensation of aromatic aldehydes and sulfonamides (Scheme 1a) [3][5][6][7][8]. Because of the poor nucleophilicity of sulfonamides, the condensation reactions generally require harsh reaction conditions involving the use of strong acids, elevated temperature, and metal catalysts. Other methods include a non

• -dehydrative reaction of aldehydes with isocyanate analogs ([3] and references therein) (Scheme 1b) and an oxidative reaction of primary benzylic alcohols with sulfonamides or chloramine-T ([3] and references therein), and although they are elegant, they use substrates that are not readily accessible or toxic

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• , sulfonamides and aryltrifluoroborates is described. This process provides modular access to the important α-arylglycine motif in moderate to good yields and enantioselectivies. The formed α-arylglycine products constitute useful building blocks for the synthesis of peptides or arylglycine-containing natural

• products. Keywords: amino acids; asymmetric catalysis; multicomponent reaction; palladium catalysis; Petasis reaction; sulfonamides; Introduction α-Amino acids play a crucial role in every aspect of our human life [1]. They are important synthetic intermediates in the chemical industry and used for the

• palladium-catalyzed three-component reactions between arylboronic or carboxylic acids, amides or sulfonamides and different aldehyde components as attractive and broadly applicable alternative to the classical Petasis borono-Mannich reaction (Scheme 1b) [17][18][19][20][21]. Recently, we were able to extend

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• transformations. For example, bromoacetylenes were demonstrated to add imidazoles, imidazolines [12], and benzimidazoles [13][14] to give vinyl bromides. Sulfonamides reacted with bromoacetylenes to deliver N-bromovinyl-p-toluenesulfonamides that under Heck reaction conditions afforded N-(p-toluenesulfonyl

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• , sulfonyl chlorides are good building blocks to intermediates and complex scaffolds of sulfonamides. Gordon, Maskill, and Ruasse [1] have reviewed “Sulfonyl Transfer Reactions” in a broader sense than the coverage of the present contributions. In particular, an appreciable amount of the coverage in the

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• very attractive as HAT catalysts as demonstrated by previous works using secondary amides [8][9], sulfonamides [10] and quinuclidine [11][12], the latter being broadly explored in the literature for several functionalizations along with its derivatives [11][12][13][14][15][16][17][18][19][20]. DABCO is

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• catalyst wasn’t necessary to promote the reaction, but the yield of the cascade was significantly increased upon loading. The scope of the π-systems was limited to alkenes conjugated to electron-rich aryl species. Various nitrogen nucleophiles including primary/secondary amines and sulfonamides were