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

• describes several important catalytic asymmetric strategies applied to enantioselective radical reactions, including chiral Lewis acid catalysis, organocatalysis, photoredox catalysis, chiral transition-metal catalysis and photoenzymatic catalysis. The application of electrochemistry to asymmetric radical

• the 1990s. Since then, meticulous research by several research groups has led to significant advances in this area [4][5][6][7][8]. This perspective focuses on several important contributions to the science of asymmetric radical reactions. Pioneering work on chiral Lewis acid catalysis and iminium

• research on auxiliary-based chiral Lewis acid catalysis inspired Porter, Sibi and others to transpose the concept to radical chemistry. A large number of enantioselective radical reactions that were reported during 1996–2007 were mainly based on chiral Lewis acid-mediated/catalyzed free radical reactions

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• pathway-controlled approach using tryptamine ynamides bearing Michael acceptor moieties as substrates (Scheme 27) [38][39]. Under strong Brønsted acid catalysis, protonation of the carbonyl group was achieved, which facilitated a Michael addition between the electron-rich indole C3-position and the

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

• , amides, lactones, acrylic acid, etc. (Scheme 72) and is therefore a key intermediate in the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals. Levulinate esters, used as a solvent or as biofuels, are obtained by esterification under acid catalysis, e.g., with a sulfuric acid

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• that its sufficient acidity is key to the success of the reaction. Using the 2N-Troc-protected GlcN phosphite 44 as the donor and the 4,6-O-benzylidene acetal-protected 1,2-diol 45 as the acceptor afforded the β,α-disaccharide 46 with high stereoselectivity under borinic acid catalysis [62]. In

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

• metal-free annulation reaction between electron-rich 3-aryloxetan-3-ols 142 and 1,2-diols under Brønsted acid catalysis (Scheme 51) [105]. The resulting 1,4-dioxanes 218 were obtained mostly in moderate to high yields and high regio- and diastereoselectivities were achieved with unsymmetrical diols. The

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

• consequently, different catalytic strategies to afford the electrophilic addition on the final cyclization step. Finally, other examples show the synthesis of 3-aryl and alkyl quinoline-3-carboxylate derivatives under acid catalysis for the activation of DMSO via the Pummerer reaction (Scheme 10). In these

• was carried out via copper catalysis or iodine–acid catalysis. Interestingly, when aliphatic amines are employed (R3 = n-Pr, n-Bu, product 8) only the N atoms are incorporated in the structure of the final product, probably because the high temperature favors the elimination of the alkyl group. The

• -protic nature make them suitable dissolving agents for a wide range of reagents. Furthermore, the polar bond C–X can be activated by different chemical procedures (metal or acid catalysis, for example) and serves as a reactive center. In this regard, dihalomethanes can act as halogen donors in

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

• to NHC-catalyzed reactions. The major part is devoted to chiral Brønsted acid catalysis as it seems so far the most widely used activation principle for the generation of axially chiral compounds. Hydrogen-bond-donating catalysts and various other activation modes complete the discussion of recent

• 219oa (84%, 92% ee). The unique combination of photochemistry and Brønsted acid-catalysis by CPA (R)-C23 was utilized in the cyclization reaction of cinnamates 220 forming N-arylquinolones 221 (Scheme 65) [95]. Optimized reaction conditions led to the formation of products 221 in remarkable yields with

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

• out IEDADA reactions has been a glowing field in recent years [11][12]. In particular, organocatalysis can provide different activation modes to promote enantioselective IEDADA reactions [13][14], based on three strategies (Figure 3): i) LUMO-lowering activation (Brønsted acid catalysis), ii) HOMO

• Brønsted acid catalysis has been widely studied in asymmetric synthesis [38][39]. While the asymmetric transformations of 2-azadienes have been more intensively investigated, enantioselective derivatizations of 1-azadienes are scarce. In this section, the cycloaddition reactions involving α,β-unsaturated

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

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

• in a Mannich reaction [4]. In 2018, our group showed in a proof-of-principle study [5] that the Lewis acid catalysis by DAI salts is based on halogen bonding (XB), an interaction between a Lewis base (XB acceptor) and an electrophilic halogen atom in the Lewis acid (XB donor) [6][7][8][9][10]. In

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

• catalysts or photochemical procedures have been developed to enable this transformation [7][8][9]. The reactivity of hypervalent iodine reagents can be enhanced via Lewis acid catalysis [10]. For example, PIDA becomes a stronger oxidant upon coordination of BF3·OEt2, enabling chemistry that was not

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• 2356151). No significant improvement in the yield was observed by varying the reaction conditions. Surprisingly, the reaction of 1,3-diketone 1a, morpholine and acetone without the use of molecular sieves and acid catalysis (conditions A) resulted in 81% yield of meta-substituted aniline 3ab. Applying the

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• in shape and polarity of the structures. This is reversible using blue light (460 nm, AzoTAB only), heat (Δ) or acid catalysis (both AzoTAB and AAPTAB). In-situ UV (365 nm) irradiation results in sequential change to the SAXS patterns for (c) AzoTAB and (d) AAPTAB (both 50 mM in water), attributed to

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• numerous modified techniques, which established the greener side of the reaction. The use of Lewis acid catalysis in this regard [34][35][36][37][38][39] played a significant role, which also suppressed the epimerization in the case of chiral molecules. Among the various Lewis acid catalysts such as

• methodologies, such as Lewis acid catalysis, desymmetrization of symmetrical dialdehydes, synthesis of natural products, and building blocks. These modifications constitute the main highlight of this review. The use of modern technology and newer strategies aiming towards industrial benefit is the goal for the

• , and amide, etc. functionalities. The vast area of synthetic venture highlights the significance of this reaction, as exemplified here, in some of the most recent advances of this reaction during the last two decades. Proper utilization of Lewis acid catalysis, desymmetrization of symmetrically remote

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• substrate. Employing Lewis acid catalysis Deng and co-workers reported an alternative pathway to indole-derived BCHs. Polysubstituted BCHs were accessed by nucleophilic addition of the indole to the activated bicyclobutane followed by a Mannich cyclisation [81]. The synthesis of wide variety of tri- and

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

• activities. The most direct way of obtaining this nucleus is the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between aminopyridines, aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis. However, several catalysts for this reaction have major drawbacks such as being

• conditions and the employment of relatively complex starting materials [19]. A more efficient way of obtaining this nucleus is through the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between amidines (aminoazoles), aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis [20

• ][21][22]. Multicomponent reactions (MCRs) provide one-pot reactions, simple synthetic procedures, less waste being produced, fewer purification steps, and a high atom economy [23]. The GBB three-component reaction is carried out in the presence of Lewis or Brønsted acid catalysis to increase the

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

• both within the context of a classic gold π-activation/protodeauration mechanism and a general acid-catalyzed mechanism without intermediate gold alkyls. Keywords: alkene hydroamination; general acid catalysis; gold catalysis; isotope effect; phosphine ligand effect; solvent effect; Introduction

• competing Brønsted acid catalysis in gold-catalyzed alkene functionalization remains a consideration [2], and while it is assumed that alkene activations follow the same prototypical mechanisms as allene and alkyne activations, that is (1) π-activation with nucleophilic attack followed by (2

• 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

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

• highest fungicidal activity [11]. Brønsted or Lewis acid catalysis – conventional synthetic methods The indole moiety is part of many natural products, agrochemicals, and pharmaceuticals. In medicinal chemistry, indole and its derivatives are considered important compounds, since they exhibit valuable

• of green chemistry. Organocatalysis is the acceleration of chemical reactions with the use of small organic compounds, which do not contain any amounts of enzyme or inorganic elements [37][38][39]. The benefits of solid acid catalysis render them as an appealing choice, compared to their liquid

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

• . With this mechanistic blueprint as a backdrop, Phipps and co-workers developed an enantioselective Minisci-type addition, under dual photoredox and chiral Brønsted acid catalysis [44] (Scheme 5A). In their proposed mechanism, the activation of the NHPI ester radical precursor was proposed to occur via

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• diazocarbonyl reagent is presented for the first time. The protective group is removed without acid catalysis with near quantitative yields. New benzotriazole derivatives containing functional groups capable of participating in the subsequent modification for linker attachment to assemble the PROTAC molecule

C–H bond functionalization: recent discoveries and future directions

• Indranil Chatterjee

Beilstein J. Org. Chem. 2023, 19, 1568–1569, doi:10.3762/bjoc.19.114

• its combination with organometallic chemistry for site-selective C−H bond functionalization [3][4]. Recent years have witnessed many viable strategies for the synthesis of complex targets utilizing photoredox catalysis, electroorganic catalysis, Lewis acid catalysis, and transition-metal-free

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

• nucleophilic attack of TMSN3 to deliver product 11 (Scheme 7). Tian and Chang et al. could synthesize 3‑sulfenylated coumarin compounds 13 by using N-sulfanylsuccinimides 1 under a Lewis acid catalysis system (Scheme 8) [48]. Additionally, oxidation of 3-sulfenylated coumarins utilizing (diacetoxyiodo)benzene

• -(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

• formation of three-membered cyclic sulfonium ion II followed by ring-opening of sulfonium ion and intramolecular cyclization. The use of a Lewis base/Brønsted acid catalysis system for the sulfenylation of aromatic substrates 4 was reported by Gustafson et al. (Scheme 55) [87]. In the method, catalyst P

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

• with mCPBA produced the epoxide 13.3. Then, the addition of benzoic acid in the presence of acid catalysis produced an ester that was saponified to yield the diol 13.4. A three-step sequence is applied to produce compound 13.5 that features a secondary alcohol protected with a benzyl group. Then, the

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• alkenes under chiral BINOL-derived Brønsted acid catalysis has been studied by Houk and Rueping in 2014 [33]. These authors established the origin of the enantioselectivity and the differences between the catalyzed and uncatalyzed reactions, suggesting that the catalyzed reaction is, actually, a so-called

• and co-workers demonstrated for transannular Diels–Alder cycloaddition reactions of symmetrically tethered large systems (10–18-membered rings) [29]. In this context, we have recently reported the transannular enantioselective (3 + 2) cycloaddition of cycloalkenone hydrazones under Brønsted acid

• catalysis in route to enantiomerically pure bicyclic 1,3-diamines (Scheme 1) [29]. The reaction led to excellent results when decalines and octahydro-1H-indene bicyclic scaffolds were formed (series a and b) but failed in other cases (series c, d, and k). Series e, f, g, h, and i have not been tested

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• optical activity difficult, especially if minor contaminants falsify these data. Furthermore, the variability of the optical rotations given in the literature may be a consequence of mixed enantiomeric compositions arising from contaminations of enzymatically formed 11 with 11 generated upon acid

• catalysis during compound isolations. The reporting of (–)-11, (+)-11 and 11 of unspecified absolute configuration all under the same CAS number (473-04-1) adds to the confusion. Moreover, one report is available that mentions the isolation of 11 from Atractylodes macrocephala [87]. For unclear reason, this