Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• decreasing the oxidation potential. A range of functional groups, such as halides, ethers, and heterocycles, were tolerated well, yielding the corresponding enantioenriched products 14 with high enantioselectivity in the presence of chiral bisoxazoline ligand L2. A possible mechanism is depicted in Figure 5

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

• obtain cyclic ether-fused tetrahydroquinolines 24 has been reported starting from secondary anilines, cyclic ethers and paraformaldehyde (Scheme 18) [35]. In addition to Cu(OTf)2 as a catalyst, the most effective reaction conditions required a substoichiometric amount of p-nitrobenzoic acid as an

• additive. Some control experiments support a mechanism whose key intermediates are the formation of the iminium ion XIX, originated from aniline with formaldehyde which serves as the C1 building block, and the generation of the cyclic α,β-unsaturated ethers XX by Cu(OTf)2-catalyzed dehydrogenation of the

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

• -Breslow-type intermediates with the chiral NHC-catalyst and subsequent deprotonation toward the nitrile product. Zhang, Wang, Ye, and co-workers utilized NHC-catalysis for the atroposelective synthesis of axially chiral diaryl ethers 59 and 61 [38]. This transformation was realized via desymmetrization of

• prochiral 2-aryloxyisophthalaldehydes 57a,b with a range of aliphatic and aromatic alcohols 58a–g, as well as heteroaromatic amines 60 (Scheme 19). Chiral diaryl ethers of this type received increased attention lately. Biju, Gao, Zhang, and Zeng groups all reported high degrees of yields and

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• multi-substituted benzo[j]fluoranthene derivatives, which have the potential to be useful in natural product synthesis. However, all oxygens in compound 18 are protected as methyl ethers, and therefore, demethylating one or some of these methoxy groups selectively is anticipated to be extremely

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

• and enantioselectivities. Later in 2021, Fernández-Salas, Alemán and co-workers developed a bifunctional squaramide-catalyzed enantioselective inverse electron demand aza-Diels–Alder reaction (IEDADA) between benzofuran-derived azadienes and silyl (di)enol ethers [33]. This work provides a useful

• reaction of isocyanoacetates and saccharin-derived 1-azadienes. Enantioselective squaramide-catalyzed asymmetric IEDADA reaction of benzofuran-derived azadienes and silyl (di)enol ethers. Scale up and derivatizations of benzofuran-fused 2-piperidinol derivatives. Dihydroquinine-derived squaramide-catalyzed

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• ] developed artificial, ‘natural-like’ polyphenols, using the Ugi reaction, since it leads to mixed polyphenol–peptidomimetic structures (Scheme 4). The procedure involved an Ugi reaction using phenolic building blocks protected as allyl ethers, followed by deprotection, acetylation, and high-yielding

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

• via electrochemical oxidation of 4-iodotoluene at the anode, in a 5:6 HF:amine mixture to cyclise a range of phenolic ethers 33. Tolerance for substituents on both the aromatic ring and the alkene were shown, although the electronic requirements were quite narrow for reaction success. As the arene

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• Metal-free tetrapyrrolic macrocycles as supramolecular organocatalysts Supramolecular organocatalysis has recently attracted emerging attention as a green alternative to metal-based catalysis [24][25][26]. Organocatalysis using macrocyclic scaffolds such as crown ethers, cyclodextrins, cucurbiturils

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• )] [40]. Introduction of the tert-butylperoxy fragment into the allylic position of substituted cyclohexenes 6 was carried out using Pd(OAc)2 in ambient conditions (Scheme 5) [41]. The corresponding allylic peroxy ethers 7 were synthesized in 62–75% yields, the key intermediate was proposed to be L2Pd(OO

• tert-butylperoxy radical В. Fe(acac)3-catalyzed oxidation of benzyl, allyl and propargyl ethers 78 with TBHP led to the formation of tert-butylperoxyacetals 79 (Scheme 28) [75]. Probably, in the first step TBHP oxidizes Fe(II) to Fe(III) with the formation of tert-butoxy radical A. Then the second

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

• ) to iodine(I). Intermediate II then undergoes an intramolecular aryl migration, yielding the diarylated products 41, analogous to the known iodoniumphenolate reactions that produce diaryl ethers. The same research group meliorated the N-arylation of aliphatic cyclic amines with the same fluorinated

• reaction that results in the formation of diaryl ethers. Diaryl ethers are important structural motifs in pharmaceuticals and agrochemicals due to their diverse biological activities. Since the 1950s, one of the most used methods for the synthesis of diaryl ethers involves the reaction of phenol with

• . A synthetic protocol for diaryl ethers via an in situ generation of a hypervalent iodine salt was introduced by Stuart and co-workers in 2020. To study the scope of the reaction first various substituted aryl(TMP)iodonium salts 12 were reacted with different substituted phenols 61 in the presence of

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• Jinbo Ke Pit van Bonn Carsten Bolm Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.20.235 Abstract We present a mechanochemical synthesis of difluoromethyl enol ethers. Utilizing an in situ generation of difluorocarbenes, ketones are

• reactions of difluorocarbene with cyclic and acyclic 1,3-diones (Scheme 1A) [41][42][43][44][45]. Typically, they were conducted with a base to form the corresponding enolate anions which then reacted with difluorocarbene to yield difluoromethyl enol ethers. Those products are of interest because they

• contain a unique structural motif with potential for further functionalizations into highly diverse secondary or tertiary difluoroalkyl ethers. Dolbier and co-workers investigated reactions of difluorocarbene generated from its precursor trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate (TFDA) and

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluoroenynes via Suzuki–Miyaura and Sonogashira cross-coupling reactions using novel multihalogenated fluorovinyl ethers, which are easily prepared from the reaction between phenols and 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane). These reactions make use of the unique structure of multihalogenated

• fluorovinyl ethers, which contains a reactive bromine atom, to afford a series of fluoroalkenes and fluoroenynes in moderate to high yields. Keywords: fluoroalkenes; fluoroenynes; multihalogenated vinyl ethers; Suzuki–Miyaura cross-coupling reactions; Sonogashira cross-coupling reactions; Introduction

• development of a dual-reactive fluorine-containing C2-unit, which was prepared from trifluoroethanol in two steps in 63% yield, allowed the convergent synthesis of fluoroalkenes (Scheme 1C) [26]. We recently found multihalogenated vinyl ethers 1 could be obtained by the reaction of phenols with 2-bromo-2

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• components, carboxylic acids, alcohols, glycerol ethers, amides, and volatile compounds such as phenol, benzaldehyde, or indole were present (Figure 1 and Table 1). While some of these compounds were easily identified, a group of diketopiperazines (DKPs) and a series of unknown putative carboxylic acids (A–F

• bicolor [8]. These ethers are also found in the scent glands of other reptiles such as lizards [40] and probably act as detergents to increase the solubility of apolar lipids. Amides have been found in Dumeril's Boa and the western diamondback rattlesnake, among others [5][11]. The secretion has also been

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

• > secondary. Functional groups such as silyloxy, amides, ethers, esters, enolizable ketones, and nitriles were found to be compatible with this transformation. Late-stage functionalization of different molecules was demonstrated; for example, the azidation of ibuprofen occurred preferentially at the secondary

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• trifluoromethoxylations of (hetero)aromatics [47][48][49][50][51][52], enol carbonates [53] or silyl enol ethers and allyl silanes [54] have been reported. Most of the methods described have used the trifluoromethoxide anion (CF3O−) [45]. Many sources of the CF3O− anion have been described, but with certain drawbacks

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• ][9][10][11], yielding phenylacetic acids. For example, Troupel et al. successfully performed electrochemical reduction of benzyl ethers and several esters such as acetate, trifluoroacetate, benzoate, and dibenzyl carbonate derived from benzyl alcohols, including 1-phenylethanol compounds, in the

• mandel acetates [14], respectively. Electrolysis of styrene oxide and related 2-phenylcyclic ethers in the presence of carbon dioxide also induced carboxylation at the benzylic position by reductive cleavage of a C(sp3)–O bond to give the corresponding ω-hydroxy-2-phenylalkanoic acids [15][16]. In

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• with diketenes (Scheme 1b, path 3) [35] as well as isocyanates with various nucleophilic reagents (Scheme 1b, path 4), such as silyl enol ethers [36], enamines [37], α-acylphosphonium ylides [38] and lithium enolates [39]. Recently, the hydrolysis of α-oxo ketene N,S-acetals was developed to prepare

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• fecal microbiota [107]. Alternariol methyl ethers: Methyl ethers of alternariol have been obtained during chemical structure elucidation and as intermediates in total syntheses of natural products, but some of these have been furthermore isolated as natural products (Figure 5). First to mention is 9-O

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• sodium methoxide in an undivided cell, three main products (namely benzophenone dimethyl acetals 133, diphenylmethyl methyl ethers 134 and diphenylmethanes 135) were obtained, the ratio of which was influenced by the electrode materials, the temperature and the amount of sodium methoxide. The range of

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• reactions were not described at all. Nevertheless, the radical reactions are the most powerful instrument for the preparation of new molecules with a CHF–CHF fragment. For instance, the radical addition of hypohalites is a suitable high-yielding approach toward polyfluorinated aliphatic ethers and esters

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

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

• respective isomers where the geometry of the 1,3-distal dialdehyde 35 was conformationally favorable for the intramolecular hydride attack to take place leading to the formation of the product (Scheme 16). Symmetrical crown ethers having two aldehyde groups 39–42 were functionalized and desymmetrized by

• [4]arene dialdehydes. Desymmetrization of dialdehydes of symmetrical crown ethers using Ba(OH)2. Synthesis of ottelione A (proposed) via intramolecular Cannizzaro reaction. Intramolecular Cannizzaro reaction for the synthesis of pestalalactone. Synthetic strategy towards nigricanin involving an

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• photochemical C–O bond cleavage of ethers in organic transformations has attracted considerable interest. In this context, in 2018, Nicewicz and co-workers [57][58] reported a visible-light-photoredox-catalyzed single-step synthesis of polysubstituted aldehydes using easily accessible olefin substrates (Scheme

•  21). Styrenes selectively reacted with vinyl ethers in the presence of an acridinium photocatalyst and a diphenyl disulfide HAT catalyst to produce the aldehyde product when exposed to blue LED light. Differently substituted styrenes were examined using this protocol, which produced the aldehyde

• products in good yield (i.e., 80a–d, 48–80%). Cyclic olefins also performed well under these conditions and generated products with a β-ring moiety (i.e., 80e–g, 60–64%), which would have been challenging to synthesize otherwise. 2-Substituted ethyl vinyl ethers also provided α-branched aldehyde products

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• of the substituent located at carbon C3 of the chromone moiety and also on the type of nucleophile employed. Keywords: cyclizations; 1,3-dicarbonyl compounds; domino reactions; heterocycles; regioselectivity; silyl enol ethers; Introduction Domino reactions (also called cascade or tandem reactions

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• 4bo (o-phenoxy and o-bromo group, respectively), the er dropped considerably. Finally, a strong electron-withdrawing group in the ortho position such as nitro (4bn) was met with a decrease in yield (66%), but with a higher er. During the development of the scope, the hemiaminal ethers (Heck–Matsuda

• elimination of methanol favored by the evaporation process. The instability of hemiaminal ethers was previously described in literature [19] during work-up. We then found that careful control of the drying conditions, thus avoiding complete drying of the crude mixture prevents degradation of the Heck products