Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• equivalents of aqueous NaOH in EtOH, afforded (−)-preaustinoid B2 (83) with 95% yield. Using 0.4 equivalents of aqueous NaOH, a mixture of (−)-preaustinoid B1 (82) and (−)-preaustinoid (83) was obtained (Scheme 15). Nagaraju and Prasad used the α-ketol rearrangement mediated by Lewis acids to carry out the

• reagent 118 using trifluoromethanesulfonic acid (TfOH) or TMSOTf as Lewis acids. The authors suggested that the reaction proceeded via the formation of an intermediate 119 followed by reaction with an alcohol nucleophile and a 1,2-carbon migration to produce a cyclopentane derivative 120 with a yield of

• stereospecificity of the reactions. Lewis acids usually initiate this transformation, and the reaction is most efficient when there are electron-accepting groups present. Sometimes, the rearrangement of epoxides into cyclopentane is accompanied by competing reactions – the formation of cyclohexanone/ols – which are

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• -benzoquinone – advanced 41 to neoavarone (44). After screening various Lewis acids (including AlCl3, Mg(OTf)2, Yb(OTf)3, etc.), it was finally found that treatment of 44 with irradiation at 422 nm in the presence of the optimal Lewis acid LaCl3 furnished the natural products dysiherbol A (33) and dysideanone E

• spin-center-shift (SCS) process in forming the core of septosone B (47) [32][33]. The influence of Lewis acids is partially attributable to two effects: (1) the observed elongation of the lifetime of the singlet excited state (from 0.846 ± 0.015 ns to 0.912 ± 0.014 ns), which reduces undesired

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• catalysts. The drawbacks of chiral Lewis acids have been overcome to an extent using organocatalysis. The use of photochemistry to generate radicals by light-induced electron transfer has resulted in elegant enantioselective radical transformations. Several transition-metal photocatalysts [9] and organo

• ) [40]. The reactions were catalyzed by chiral Lewis acids and involved conjugate addition of a nucleophilic alkyl radical to an α,β-unsaturated substrate containing an oxazolidinone or pyrrolidinone template. The resulting α-radical was trapped with an allylstannane and the addition and trapping

• occurred in an anti fashion. Products were obtained with up to 97% ee via catalysis by complexes of magnesium or copper(II) with ligand L1. The absolute stereochemistry of the product could be controlled by a simple change from copper(II) to magnesium Lewis acids while using the same chiral ligand, thus

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• pharmaceutical and agrochemical industries [38][39]. Various types of catalysts are used to enhance the efficiency and selectivity of the Knoevenagel reaction, including Lewis acids, ureas/ thioureas, amino acids, and bases such as alkali metal hydroxides, alkali metal alkoxide, amines, etc. [37][40][41][42][43

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• (Table 1, entry 2). We were delighted to observe that, in methanol, the reaction proceeded smoothly, affording 41% and 51% isolated yields of 3a and 3a′, respectively. We further explored the effect of other catalysts on the reaction. As listed in Table 1, entries 3–6, among the Lewis acids surveyed

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• for the Diels–Alder cycloaddition reaction between isoprene and methyl acrylate catalyzed by Lewis acids. Bond distances are given in angstroms and NICS(3, +1) values in ppm. Comparative activation strain analyses (a) and energy decomposition analysis (b) of the Diels–Alder cycloaddition reaction

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• and green direct C–H amination of benzoxazoles can be catalysed by copper chlorine salts in acetonitrile in the absence of any acidic, basic, or oxidising additives. Both CuCl and CuCl2 have been found to be highly efficient in promoting the reaction, on the base of their activity as Lewis acids and

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• –base reaction. Cyclization of alkynes: The extension of π-conjugation in polycyclic aromatic hydrocarbons (PAHs) through alkyne-benzannulation reactions has become an increasingly popular method in recent years [91]. Such benzannulations can be mediated by Brønsted acids, Lewis acids or transition

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• ) [6]. This methodology enabled the selective functionalization of one or two C(sp3)–H bonds adjacent to the nitrile group, leading to the formation of diverse polycycles with high selectivity. Various reaction parameters were systematically examined, including Lewis acids, oxidants, bases, reaction

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• (II) chloride and bromide (Table 1, entries 10 and 13) the formation of acetophenone as the main reaction product was observed. Presumably, in the presence of these salts, which can act as Lewis acids, the hydrolysis of the enol acetate 1a proceeds faster than the generation of the corresponding P

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• in 1,2-dichlorobenzene at 180 °C for 4 h, which gave 8a in 85% conversion and 82% isolated yield (Table 1, entry 3). Other solvents like toluene and xylene gave minimal or no product. Different combinations of temperature and reaction time couldn’t improve the yield. Among the various Lewis acids

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