Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• ] cycloaddition step that ends with aromatization through a 1,3-H shift (Scheme 31) [84][85]. These compounds are highly relevant biological scaffolds for drug discovery [84]. In general, this reaction works very well with a wide variety of Lewis acids (as Sc(OTf)3 and MgCl2) and Brønsted acids (e.g., NH4Cl and

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

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

• . Among various Lewis acids, only Cu(OTf)2 in combination with TMSCN was effective or a valuable alternative was the use of acetone cyanohydrin combined with a catalytic amount of TEA (5 mol %). The mechanism involves the formation of an imine facilitating the addition of the nitrile group. Among the

• reaction of isatin, 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one (i.e. kojic acid) and malononitriles or cyanoacetates (Scheme 32) [51]. Compared to other Lewis acids, Cu(OTf)2 proved to be the best. Mechanistically, the process begins with a Knoevenagel-type condensation between isatin and the cyano

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

• -heterocycles using various catalytic systems such as chiral metal catalysts, chiral Lewis acids or chiral organocatalysts. This review presents an overview of the recent advances in enantioselective cyclization reactions of 1-azadienes catalyzed by non-covalent organocatalysts. Keywords: α,β-unsaturated

• 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

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

• in aryl-transfer processes, DIAS are frequently employed as photoinitiators for cationic polymerizations [31][32][33], Lewis acids [34], oxidants [35][36] and in the field of macromolecular chemistry [37][38]. Additionally, biological activity is also exhibited by iodonium salts, often due to their

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• an in silico approach to design asymmetric frustrated Lewis pairs (FLPs) aimed at controlling reaction stereochemistry. Four FLP scaffolds, incorporating diverse Lewis acids (LA), Lewis bases (LB), and substituents, were assessed via volcano plot analysis to identify the most promising catalysts. By

• pairs tailored specifically to control the stereochemistry of the CO2 insertion reaction. Computational evaluations of four distinct FLP scaffolds, incorporating various Lewis acids, Lewis bases, and substituents, identify the most promising catalyst candidates through volcano plot analysis. The volcano

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• organocatalysis, previously only iodine(I)-based Lewis acids had been applied. However, after this study, the application of DAI salts as XB donors gained increasing interest and was investigated by several groups [11]. In the last years, important information about structure–activity relationships was also

• obtained: in a titration study by Mayer and Legault it was determined that cyclic five-membered DAI salts, so-called iodolium compounds, are significantly stronger Lewis acids than their less-stable acyclic counterparts [12]. By using the activation of alkyl halides as a benchmark, our group later reported

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• experimented with Lewis acids (Table 1, entries 10–12) to catalyze the reaction and observe low conversion with SrCl2. The reaction was significantly better with both La(NO2)3 and Yb(OTf)3 under solvent-free conditions (Table 1, entries 11 and 12, yield 61–65%). The most promising results were obtained by

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

• catalysts Noncovalent organocatalysts display a few advantages compared to the traditional metal Lewis acids, such as lower environmental impact, higher stability to air and moisture, easier removal from the GBB products. In this regard, Bolotin et al. in 2022 have reported the high catalytic activity of

• Suzuki–Miyaura reaction and then subjected the adduct 52 to a GBB reaction with various aldehydes and isocyanides (Scheme 20) [53]. Focusing on the GBB part, the authors tested both Lewis acids (Sc(OTf)3 or Yb(OTf)3) and Brønsted acids (NH4Cl or AcOH) and found that the best results could be obtained

• active ones by DNA sequencing. Great challenges, however, characterize the synthetic methodologies, since the chemistry must display a broad scope, be compatible with water and operationally simple, and preserve the genetic information (i.e., no harsh conditions, strongly acidic pHs, no oxidants or Lewis

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• was significantly enhanced when refluxing in DMF with a catalytic amount of AlCl3 compared to the reaction in clear DMF (Table 1, entries 7–9). Other Lewis acids were not as effective, except for a combination of DMSO/TMSOTf (Table 1, entry 4). The application of AcOH/PPA for the synthesis of 5

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• added to 3a (Scheme 3a). Formation of hemiketal 8 was expected to occur, which would facilitate ring opening by a 5-exo-tet cyclization. While we did observe the formation of hemiketal 8 by NMR spectroscopy, we were unable to detect any ring-opened products 9, even when adding Lewis acids or Brønsted

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• , 2a could be fully converted and the 2-benzylaniline 4aa was obtained in 52% yield after 46 h (Table 1, entry 1). Some commonly used acid catalysts were tested, however, neither Brønsted acids such as AcOH and TsOH, nor Lewis acids such as FeCl3 and BF3·Et2O, showed a promoting effect on the aimed

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• goal, different Lewis acids (10 mol %) such as Zn(OTf)2, CuCl2, and FeCl3 were screened at room temperature in different solvents, employing compound 4a as the model substrate (Table 1). From the set of data collected, both the formation of N,O-aminal 5a and corresponding hemiaminal 6a were observed

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• electrocyclization reaction could be mediated by weaker Lewis acids, and consequently a catalytic amount of them could be used. The first example of a catalytic version of the Nazarov cyclization was reported by Denmark and Jones [25][26][27][28][29][30][31]. They found that a substoichiometric amount of FeCl3 (40

• first asymmetric catalytic Nazarov reaction [32]. In recent years, several strategies were reported employing different Lewis acids, such as, AuCl3/AgSbF6, Cu(II), In(OTf)3, Ir(III), Al(III), Sc(OTf)3/LiClO4, In(OTf)3/diphenylphosphoric acid (DPP), Fe(OTf)3/(CF3)2PhB(OH)2, iodine [33][34][35][36][37][38

• ][39][40][41][42][43], and other strategies [44][45]. Although methodologies involving catalysis by Lewis acids are very efficient, including asymmetric versions of the Nazarov reaction, the experimental protocols are quite laborious in most cases, requiring low temperature, an inert atmosphere, or the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• a side note, it should be mentioned that Hutchings and colleagues reported the hydrochlorination of ethylene with Lewis acids on solid supports [52]. However, this work solely focuses on kinetic studies and is therefore not discussed in this report. Reactions with in situ-generated HCl HCl gas can

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• reactivity of the imine formation [24]. The most common catalysts are those derived from triflate salts such as Sc(OTf)3 [25], Yb(OTf)3 [26], In(OTf)3 [27] and Gd(OTf)3 [28], and inorganic Brønsted or Lewis acids like HClO4 [29], ZrCl4 [30], InCl3 [31], BiCl3 [32], RuCl3 [33], NH4Cl [34], HCl [35], LaCl3

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

• -inflammatory, and even anticancer agents. Traditionally, the synthesis of BIMs has been achieved upon the acidic condensation of an aldehyde with indole, utilizing a variety of protic or Lewis acids. However, due to the increased environmental awareness of our society, the focus has shifted towards the

• or Lewis acids as catalysts. In 2010, Shiri published a review, where the majority of the acidic catalysts that have been employed for the synthesis of these compounds were presented [12]. Since then, various alternative acids have been applied including protic acids, such as silica-bonded S-sulfonic

• well as Lewis acids, such as FeCl3 [23][24], RuCl3·3H2O [25], AgNO3 [26], glycerol and [Fe(III)-(salen)]Cl [27], Fe(DS)3·nH2O [28], Sc(OTf)3 [29], B(C6F5)3 or PhSiCl3 [30] and Cp2TiCl2 [31]. However, most of these reactions face some serious drawbacks, such as the requirement of large quantities of the

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• electrochemical conditions and can be influenced by a number of factors, including the nature of the electron donor, the use of Brønsted and Lewis acids, and the possibility of forming charge-transfer complexes. Such versatility creates many opportunities to influence the reaction conditions, providing a number

• transfer complexes with a donor species 6 or via LUMO lowering activation with Brønsted and Lewis acids 7 (Scheme 2B), collectively offering a number of variables to influence their reactivity. Upon reduction, RAEs give rise to a radical anion 8 with a weakened N–O bond (BDE < 70 kcal/mol) [33]. While

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• ], Pd(II) [31][32][33], Pt(II) [34][35], Fe(III) [36][37], Cu(I) [38][39][40][41], Co(III) [42][43][44], as well as other metals, have been widely studied. In addition, methods involving Brønsted acids, alone or in presence of Lewis acids as co-catalysts, have been developed [45][46][47][48][49][50][51

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• ). When 5 equiv sodium nitrite were used, the corresponding yield was also decreased (Table 1, entry 4). Other Lewis acids employed in the reaction were less effective than AlCl3 (Table 1, entries 5–7). Furthermore, solvent screening showed that DMAc was the best reaction medium for this cycloaddition

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

• imidated product 32. In 2018, an Fe-catalyzed carbosulfenylation and carboselenylation 33 of alkenes with N-(thio/seleno)phthalimides 14 was introduced by Lv and Li (Scheme 17) [54]. The use of Lewis acids, such as AlCl3, ZnCl2, InCl3, Fe(OTf)2 and Fe(acac)3 was not beneficial. However, BF3·OEt2, SnCl4

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

• ; 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

• ][4][5][6][7][8][9][10]). Protonation (or coordination) of basic centers (carbons of unsaturated bonds and heteroatoms) of organic molecules in Brønsted (or Lewis) acids gives rise to not only monocations, but also to highly reactive dicationic (and even higher charged) species. Thus, different

• Brønsted and Lewis acids were also tested for this cyclization. Thus, enones 2a and 2e were not transformed into the corresponding indanones 3 in neat sulfuric acid (H2SO4) at room temperature for 3 days. That is in accord with literature data [19], where H2SO4 was used for dehydration of hydroxy ketones 1

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

• properties of transition metals and Lewis acids [69][70][71][72]. These advantages make iron salts attractive catalysts or reagents in chemical transformations and are considered ideal materials for developing catalysts [73]. Fe-catalyzed CDC reactions have achieved remarkable achievements in recent years

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• these substrates and the formation of water as the sole non-toxic byproduct in the reaction [11]. In general, the previous methods for the amination of MBH alcohols needed catalysts or additives such as FeCl3 [12][13], In(OTf)3 [14], MoCl5 [15], AuCl3 [16], and I2 [17] as Lewis acids. Alternatively

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