The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• demonstrated that the use of triflimide (Tf2NH) in solvents like CH2Cl2, acetonitrile or toluene at −78 °C yielded exclusively the 1,2-trans stereoselective glycoside product 105 (protocol A, Scheme 18), while the use of triflic acid (TfOH) in ether as the solvent at ambient temperature conditions (protocol B

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

• emerged among copper catalysts because it can act as a precursor to triflic acid in addition to a powerful copper-catalytic effect. Indeed, Cu(OTf)2 has proven to be an excellent surrogate for triflic acid compared with other metal triflates because it is inexpensive and exhibits high activity with low

• involves a Friedel–Crafts alkylation of the arene followed by hydroamination (Scheme 6) [5]. The mechanism plausibly starts with the in situ formation of triflic acid from Cu(OTf)2 which leads to protonation of the oxygen atom of the alcohol with generation of the activated allyl alcohol. This latter gives

• the allyl carbenium ion VI through the loss of a molecule of water, then undergoes a Friedel–Crafts alkylation by attack of the aromatic partner. The outcome of the reaction proceeds through a Markovnikov protonation of the allylated arene VII by triflic acid, which generates the carbocation

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• Barton–Kellogg reaction with 8b under similar conditions gave the episulfide intermediate, which, however, could not be desulfurized with triisopropyl phosphite, trimethyl phosphite or triphenylphosphine to give the corresponding triene. The subsequent Scholl reaction of 10 with DDQ and triflic acid at

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• titrations the moisture and oxygen contents in argon were always under 10 ppm during measurements. Triflic acid (Aldrich, 99+%) and phosphazene base P2-Et (165535-45-5, Aldrich, ≥98%) were used to prepare the acidic and basic titrant solutions, respectively. Acetonitrile (Romil 190 SpS far UV/gradient

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• active catalytic species in COBI-catalysed allylations, chemical equilibria in a solution containing catalyst 72, triflic acid, and aldimine 73 were investigated by low-temperature NMR spectroscopy (Scheme 15). Protonation of oxazaborolidine 70 with triflic acid resulted in an 8.3:1 mixture of 71 and 72

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• use of triflic acid (TfOH) resulted also in the cleavage of the alkyl group derived from the isocyanide, with formation of 47 (Scheme 18). Kanizsai et al. [51] have reported the synthesis of 4,5-disubstituted 2-amino-1H-imidazoles and their further modification through the GBB-3CR. The 2

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• electrolysis cell. Thioglycoside 14 (0.40 mmol, 186 mg), Bu4NOTf (1.0 mmol, 393 mg), DTBMP (2.0 mmol, 411 mg), and dry CH2Cl2 (10 mL) were added to the anodic chamber. Triflic acid (0.4 mmol, 35 μL) and CH2Cl2 (10 mL) were added to the cathodic chamber. Electrolysis was performed at −20 °C under constant

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

• were shown to proceed with anti-selectivity and that was used as support for gold catalysis [15], but mechanism studies of triflic acid catalysis showed a preference for anti-selectivity as well [31]. Despite similarities, control studies indicate meaningful differences in catalytic activity between

• catalyzed by triflic acid and the gold π-activation pathway was questioned [26]. Nevertheless, advancements in gold-catalyzed reactions continued to be achieved. In particular, successful asymmetric methods were reported in short time after initially reported non-asymmetric methods, specifically Kojima’s

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• acid [13], polyvinylsulfonic acid (PVSA) [14], kaolin-supported H2SO4 [15], polyvinylpolypyrrolidone-supported triflic acid (PVPP.OTf) [16], ascorbic acid [17], phosphoric acid [18], benzenesulfonic acid [19], chitosan–SO3H (CTSA) [20], phthalimide-N-sulfonic acid (PISA) [21] and SiO2-KHSO4 [22] as

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• -enones) undergo intramolecular transformation into 3-trichloromethylindan-1-ones (CCl3-indanones) in Brønsted superacid CF3SO3H (triflic acid, TfOH) at 80 °C within 2–10 h in yields up to 92%. Protonation of the carbonyl oxygen of the starting CCl3-enones by TfOH affords the key reactive intermediates

• ; indanones; trichloromethyl group; triflic acid; Introduction Superelectrophilic activation of organic compounds under the action of strong Brønsted and Lewis acids is an effective method for the synthesis of various carbocycles and heterocycles, and polyfunctional compounds (see books [1][2] and reviews [3

• =CHC(=O)Me] with arenes in Brønsted superacid TfOH (triflic acid, CF3SO3H) furnishes 3-methyl-1-trichloromethylindenes (Scheme 1a) [11]. Based on NMR analysis in TfOH and theoretical DFT calculations, it has been found that the reaction proceeds through an intermediate formation of the O-protonated

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

• functionalization. The formation of the desired products depends on the amount of triflic acid used in the reaction. Using 0.05 equivalents triflic acid gives N-sulfonylpyrroles 15 in 80–92% yields, 1.0 equivalent of triflic acid provides N-sulfonylindole 16 in 75–91% yields and 3.5 equivalents of triflic acid

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• target hexaphenylbenzene 26 in an 80% yield. Compound 26 was treated with excess DDQ (10.0 equiv) in the presence of triflic acid to furnish the fourfold cyclization product 27 in a 60% yield. Notably, no fivefold cyclized product was detected. Meanwhile, by introducing an aza-eight-membered ring in the

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• -chloroperoxybenzoic acid (mCPBA) as the oxidant of choice in the presence of triflic acid (TfOH) [27][29]. Based on these promising results, the conditions were optimized using o-benzimidazole-substituted iodoarenes 4aa and 4ah (Table 1). While running the reaction in MeCN as solvent resulted in no product formation

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• Dihydrolevoglucosenone (DLG) is prepared by hydrogenation of levoglucosenone in the presence of palladium as a catalyst. Recently, Debsharma et al. reported the CROP of levoglucosenyl alkyl ether in CH2Cl2 at 0 °C and at room temperature using triflic acid or boron trifluoride etherate as initiators [46][47][48]. The 1H

• (Figure 5a). We suggest that the solvent reacts with methyl triflate to form triflic acid and methylated DLG (Figure 5a). The strong acid triflic acid then can initate the polymerization with a proton [46]. Alternatively, the triflic acid could react potentially together with DLG with a monomer, leading

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• ). The use of the much stronger triflic acid actually paradoxically protects the rather sensitive indoline cycloaddition products such as the dearomatized product 100, derived from skatole (99), by keeping the adduct and all intermediates in their protonated form throughout the progress of the reaction

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• the proposed multi-step procedure since we assumed it to be the more challenging. We initially intended to oxidize and cyclize the intermediate iodoarene 2 electrochemically under batch conditions (Table 1). Through preliminary observations (see Supporting Information File 1, Table S1), triflic acid

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• mg), Bu4NOTf (1.0 mmol, 393 mg), and dry CH2Cl2 (10 mL) were added to the anodic chamber. Triflic acid (0.2 mmol, 17.6 μL) and CH2Cl2 (10 mL) were added to the cathodic chamber. Electrolysis was performed at −60 °C under constant current conditions until 0.52 F/mol of electricity had been consumed

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• cytotoxic agents. Keywords: 1,4-dihydroisoquinol-3-one; heterocyclic diazo compounds; hydroarylation; Regitz diazo transfer; triflic acid; Introduction Besides being derivatives of (or a precursor to) the 1,2,3,4-tetrahydroisoquinoline core which itself bears a special significance from the standpoint of

• -arylation reaction (Table 1) [13]. The excess of benzene was varied in the range 10 to 60 equiv and the yield of product 9a was found to improve from 63% to 83% which also allowed lowering the excess of triflic acid to 1.5 equiv. Product 9a was in all cases obtained after only 15 min reaction with high

• mixture of benzene and triflic acid. On the contrary, when adding TfOH to a solution of 10a in benzene, the formation of a complex mixture of unidentifiable products was observed, with only a trace amount of 9a detectable by 1H NMR. The formation of product 9a was unavoidably accompanied by a varying

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• strategy applying Lewis acids can be used. Among the options, bismuth triflate is a catalyst, with the additional advantages of low-cost and easy preparation from commercially available bismuth oxide and triflic acid. Quinone acylation reactions took place under mild conditions using acetic anhydride and 2

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• nine-membered rings 27 via triflic acid (TfOH)-catalyzed reaction of indole-derived phenylenediamine 25 with aldehydes 26 (Scheme 9) [19]. Mechanistically, the initially formed iminium ion I undergoes isomerization to iminium ion II through a 1,3-hydride shift process. Iminium ion III could then be

• cyclopropanes, Li and co-workers treated compound 36 with triflic acid (TfOH) in refluxing HFIP (Scheme 13) [24]. The reaction afforded compound 37 in 82% through the regioselective intramolecular ring-opening of the cyclopropane ring at the benzylic carbon atom. Very recently, our group has reported the

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• obtained 3,3-diarylpropenenitriles in triflic acid CF3SO3H (TfOH) at room temperature for 1 h are cyclized into 3-arylindenones in yields of 55–70%. Keywords: aluminum bromide; hydroarylation; indenones; propenenitriles; propynenitriles; Introduction Conjugated acetylene nitriles (propynenitriles, R–C≡C

• ]. Recently, we have shown that reactions of 3-arylpropenenitriles (cinnamonitriles, ArCH=CHCN) with arenes (Ar′H) under the superelectrophilic activation by the Brønsted superacid CF3SO3H (TfOH, triflic acid) or the strong Lewis acid AlBr3 result in the formation of 3,3-diarylpropanenitriles (Ar(Ar′)CHCH2CN

• in a similar AlCl3-catalyzed hydroarylation of an acetylene bond in the synthesis of cyclophanes [26]. Additionally, the cyclization of two selected nitriles 2c,g into 3-arylindanones 3a,b correspondingly was carried out in triflic acid TfOH (CF3SO3H) at room temperature for 1 h (Scheme 3). The

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• isomerization of N-allyl amides [20], but still possess drawbacks, especially for stereoselective synthesis of tri- and tetrasubstituted enamides. Recently, we have reported a triflic acid-mediated reaction of N-fluoroalkyl-1,2,3-triazoles leading to (Z)-β-enamido triflates [21] and Lewis acid-mediated reaction

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

• intramolecular nucleophilic attack by azide and the following deprotonation by a fluoride anion provide the final product 8 (Scheme 5). The derivatization of sulfonated aminonicotinates 8 could easily be achieved. Desulfonylation of aminonicotinate 8b proceeded smoothly in the presence of triflic acid (2.0 equiv

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• reaction of the acetylenyl-1,2,4-oxadiazoles with arenes in neat triflic acid TfOH (CF3SO3H) at room temperature for 1 h resulted in the formation of E/Z-5-(2,2-diarylethenyl)-3-aryl-1,2,4-oxadiazoles as products of regioselective hydroarylation of the acetylene bond. The addition of TfOH to the acetylene

• ; triflic acid; Introduction 1,2,4-Oxadiazoles have a great importance in chemistry, biology and medicine. Many drugs contain an 1,2,4-oxadiazole ring, such as butalamine [1], libexin [2], ataluren [3], oxolamine [4], and pleconaril [5]. Various oxadiazole derivatives show different kinds of activity

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• procedure involving the cyclization of 2-arylmethylbenzoic acid 85b with triflic acid, followed by a NaBH4-mediated reductive dehydration. Some representative examples included anthracenes 86a–g. For those interested, the cyclodehydration was also extended to 2-(arylmethyl)naphthaldehydes and 2-(arylmethyl

• methodology, they synthesized 2,3,6,7-anthracenetetracarbonitrile (90) in a good yield (84%) by double intermolecular Wittig reaction of the protected benzenetetracarbaldehyde 87 with reagent 88, followed by deprotection and double ring-closing reaction of intermediate 89; they used a mixture of triflic acid