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

• . Electron-poor and electron-rich aromatic aldehydes gave good results, whereas aliphatic aldehydes gave moderate yields (Scheme 11) [24]. The asymmetric conjugate addition of dialkylzinc and benzaldehyde to unsaturated carbonyls under copper catalysis in the presence of optically pure phosphanes was

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

• becoming increasingly relevant also in medicine. Many axially chiral compounds are important as catalysts in asymmetric catalysis or have chiroptical properties. This review overviews recent progress in the synthesis of axially chiral compounds via asymmetric organocatalysis. Atroposelective

• acids feature as the most prolific catalytic structure. The last part of the article discusses hydrogen-bond-donating catalysts and other catalyst motifs such as phase-transfer catalysts. Keywords: asymmetric organocatalysis; atropoisomers; atroposelective synthesis; axial chirality; stereogenic axis

• compounds comprising a stereogenic plane or axis is much less developed. Axially chiral compounds are well known as chiral ligands in asymmetric catalysis, with notable examples of binaphthyl-based derivatives such as BINAP, SEGPHOS, or binaphthyl-based phosphoric acid derivatives, which are among the

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• is known to be able to self-assemble in a variety of structures, including micelles, vesicles, and nanoparticles [14][15]. However, the versatility of these polymers in shaping vesicles into asymmetric structures suitable for nanomotors remains relatively unexplored. While previous research has

• demonstrated their ability to form round vesicles and some tubular shapes, the pursuit of asymmetric structures, such as the stomatocyte, presents a novel challenge and opportunity in the field [16][17]. The stomatocyte shape would be an excellent addition because of its demonstrated suitability for nanomotor

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

• Sergio Torres-Oya Mercedes Zurro Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química “Andrés M. del Río” (IQAR), Universidad de Alcalá (IRYCIS), 28805 Madrid, Spain 10.3762/bjoc.20.268 Abstract Asymmetric cycloaddition is a straightforward strategy which

• enables the synthesis of structurally distinct cyclic derivatives which are difficult to access by other methodologies, using an efficient and atom-economical path from simple precursors. In recent years several asymmetric catalytic cyclization strategies have been accomplished for the construction of N

• imines; asymmetric organocatalysis; cyclization; N-heterocycles; inverse electron demand aza-Diels–Alder reaction; Introduction Nitrogen-containing heterocycles are abundant scaffolds present in natural products, biologically active compounds, pharmaceuticals, synthetic agrochemicals, and functional

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• , the first asymmetric total synthesis of psammaplysin A was accomplished by Smith and Morrow, and the absolute configuration of compound 1 was also confirmed through organic synthesis [7]. In our ongoing research focused on uncovering new bioactive secondary metabolites from Okinawan marine sponges, we

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• transition had occurred – see Supporting Information File 1 for details.) Accordingly, we gather that the rate of cooling plays an important role whereby rapid cooling effectively "shocks" the crystal of 3, compressing the unit cell isotropically, and ultimately leads to more disorder in the asymmetric unit

• moieties in the asymmetric axis viewed along the b-axis. (B) The asymmetric unit of 3 at 90 K viewed along the c-axis. Thermal displacement ellipsoids depicted at 50% probability. Effect of [1.1.1]propellane (1) equivalents relative to SF5Cl on selectivitya. Effect of [1.1.1]propellane (1) equivalents

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

• reported by Ding and co-workers in 2021 (Scheme 19) [43]. Using fluoro benziodoxole 12 as oxidant and Zn(BF4)2 as a catalytic activator, a range of fluorinated oxazepanes were synthesised from allylamino ethanols 35 in good yields. In 2021, Jiang and co-workers reported catalytic asymmetric

• stereochemistry of the reaction. Linear chiral catalysts were found to offer higher stereoselectivity compared to spiro-catalysts. Under optimized conditions, the asymmetric aminofluorination of N-cinnamylbenzamides 37 using BF3·Et2O as the fluorine reagent demonstrated good yields and high stereoselectivity

• (Scheme 20). The scope of the reaction was probed, showcasing the versatility and applicability of the method in synthesizing chiral fluorinated oxazines. The authors proposed the mechanism of the catalytic asymmetric nucleophilic fluorination to involve the activation of iodosylbenzene by BF3·Et2O which

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

• macrocycles, both synthetic and found in nature, and their ability to act as organocatalysts, metal-free porphyrin macrocycles have a potential to be excellent candidates for green, cost-effective catalysts of various organic transformations including asymmetric synthesis. 2 Metal-free tetrapyrrolic

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• , University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146-0431, USA 10.3762/bjoc.20.255 Abstract Distilled propargyltrichlorosilane with >99% isomeric purity was prepared for the first time, and its asymmetric catalytic regiospecific addition reaction to aldehydes was developed through a

• . Accordingly, the development of efficient access to optically active chiral α-allenic alcohols continues to be of significant interest in organic chemistry [11][12][13]. The asymmetric catalytic addition of allenylation reagents to aldehydes provides direct access to chiral α-allenic alcohols in an

• toward electrophiles [14][15][16][17][18][19]. Consequently, all reported asymmetric catalytic aldehyde allenylation methods are currently limited to metal/metalloid reagents bearing R2 substituents [21][22][23][24][25][26][27][28][29][30][31][32][33][34], except for the methods with

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• . Thereafter, Takata and co-workers integrated this size-complementarity into the asymmetric framework to implement one-direction deslipping movement on the size-complementary [2]rotaxane [70]. Until 2010, only a few examples of CD-based size-complementary rotaxanes have been reported. Harada and co-workers

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

• additives. An efficient conversion was detected when the substrate contains electron-rich functionalities. In contrast, the yield dropped notably when the amines were substituted with electron-deficient functionalities. In addition, asymmetric diaryliodonium salts were examined, and the transfer of the aryl

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• reports on the preparation of chiral molecules possessing a tetrafluoroethylene unit on an asymmetric carbon center in a high optical purity, and to the best of our knowledge, only the following have been published so far (Scheme 1). As a highly enantioselective synthesis, there has been a pioneering work

• by Linclau et al. They have reported that the asymmetric Sharpless dihydroxylation of readily available (E)-5-bromo-4,4,5,5-tetrafluoro-2-penten-1-ol derivative 6 led to the corresponding chiral diols 7 with an excellent enantiomeric excess, 96% ee (reaction 1 in Scheme 1) [20][21]. It has also been

• published that the asymmetric conjugate addition of 4-methylphenylboronic acid towards (E)-5-bromo-4,4,5,5-tetrafluoro-1-phenyl-2-penten-1-one (8) in the presence of a rhodium catalyst coordinated with (S)-BINAP gave the corresponding Michael adduct 9 in 94% enantiomeric excess (reaction 2, Scheme 1) [22

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• 350100, China 10.3762/bjoc.20.232 Abstract The catalytic (asymmetric) allylation and propargylation have been established as powerful strategies allowing access to enantioenriched α-chiral alkenes and alkynes. In this context, combining allylic and propargylic substitutions offers new opportunities to

• -abundant, inexpensive, relatively stable, and low toxic. Copper-catalyzed asymmetric allylic [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and propargylic [23][24][25][26][27][28][29][30][31][32] substitutions are effective strategies for constructing new C–C and C

• ] and Nishibayashi [53] groups in 2008, Cu-catalyzed asymmetric propargylic substitutions have made significant progress [54][55][56][57][58][59][60]. The protocol allows the use of stabilized nucleophiles via the outer-sphere mechanism, and the copper allenylidene intermediate formed by copper and

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• terazosin and prazosin were successfully synthesized. Oliveira Jr. et al. developed a new methodology for the asymmetric synthesis of β-aryl-γ-lactam derivatives with very good yield and enantioselectivity [16]. This was achieved through a palladium-catalyzed Heck–Matsuda desymmetrization of N-protected 2,5

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

• strategically modifying LB substituents to induce asymmetry, a stereoselective catalytic scaffold was developed, favouring one enantiomer from both epoxide enantiomers. This work advances the in silico design of FLPs, highlighting their potential as asymmetric CCU catalysts with implications for optimising

• catalyst efficiency and selectivity in sustainable chemistry applications. Keywords: asymmetric catalysis; carbon dioxide; CO2; epoxide; frustrated Lewis pairs (FLPs); volcano plot; Introduction The field of frustrated Lewis pairs (FLPs) has flourished since their seminal discovery in 2006 by Stephan and

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• (rims) of the γ-CD cavity are blocked, but the cavity is not entirely closed. Stacked along the b axis there is a narrow channel in the cavity filled with water molecules. The conclusions are that the asymmetric unit of the crystal contains 14.1 water molecules, distributed over 23 cites, while γ-CD

• cyclodextrin cavity and in the intermolecular space. Several overlapped steps are visible on the TG curve, which is associated with the release of water molecules in several stages, with the steepest lightening of the sample at 350–370 K. Consistent with this is the DSC endothermic peak, which is asymmetric

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• , previously unobserved by microscopy, was characterised. The fit of the full model identified the one-dimensional fibres formed by the stacking of molecules, while the low-q fit identified a larger clustering feature which could be described by the formation of asymmetric multifibre braided clusters. SANS

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

• Lewis acid complex of Rh has been employed by Meggers and coworkers to functionalize the α-position of 2-acylimidazoles [55]. The reported transformation represents a successful example of a catalytic asymmetric electrosynthesis, which is typically quite challenging. The process was conducted in an

• oxidation then yields the intermediate. Subsequent desilylation and substrate/product exchange complete the catalytic cycle (Scheme 40). This approach underlines the potential of asymmetric electrosynthesis in achieving high selectivity and efficiency in complex molecule synthesis, further broadening the

• applications of electrochemical methods in organic synthesis. In this context the Meggers group developed an asymmetric Rh catalyst-promoted alkylation [56]. The Rh complex was used as a chiral catalyst and Cp2Fe as an anodic oxidation catalyst to achieve the enantioselective C(sp3)–H alkenylation of 2

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• are applicable to various substrates within the same reaction type [211][212][213][214][215]. For instance, the generality of chiral catalysts for asymmetric or enantioselective catalysis has been a longstanding interest in synthetic chemistry [216]. Angello et al. [53] applied uncertainty-minimizing

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

• equimolar chiral controller. However, recent years have witnessed the rise of asymmetric transition-metal catalysts and, importantly, organocatalytic allylation, reshaping the landscape of modern synthetic chemistry. This review explores the latest developments in the asymmetric allylation of imines

• , encompassing cutting-edge advances in hydrogen-bond catalysis and non-classical approaches. Furthermore, practical examples showcasing the application of these innovative methodologies in total synthesis are presented. Keywords: asymmetric catalysis; asymmetric synthesis; chiral amines; organicatalysis

• essential to provide a comprehensive overview of this significant topic. Review Asymmetric allylation with boron-based reagents The research on the metal-free, asymmetric organocatalytic allylation of acylimines was pioneered in 2007 by Schaus and co-workers [24]. In their elegant approach, high

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• nucleophiles in this transformation. Keywords: asymmetric catalysis; iminium catalysis; mechanochemistry; organocatalysis; thioesters; Introduction Mechanochemistry, particularly solventless processes under ball milling conditions, offers the opportunity to devise unconventional reaction pathways [1][2][3][4

• attention. The controlled formation of C–C and C–X bonds in a stereoselective fashion has found extensive application in asymmetric synthesis. Notably, the addition of malonates has attracted significant interest, albeit primarily limited to methyl or ethyl diesters [18][19][20]. The combination of iminium

• reactivity by chiral quaternary ammonium salt in the asymmetric variant of the phase-transfer catalysis. Nevertheless, no product was formed despite several conditions being examined. Finally, an attempt to activate the electrophile was performed. We chose iminium salt catalysis particularly employing chiral

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• the award of the Nobel Prize to List and MacMillan in 2021 ‘for the development of asymmetric organocatalysis’. Organocatalytic transformations have also seen the transition to industrial processes for the production of a variety of pesticides and medicinal compounds, as recently reviewed [6][7][8][9

• include the development of ACE (Asymmetric Catalyst Evaluation) [19][20], AARON (Automated Reaction Optimiser for New Catalysts) [21] or CatVS (Catalyst Virtual Screening) [22]. Such tools have been extensively reviewed in the past years [23][24][25]. Based on a known mechanism, the tools calculate the

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• applications in organic chemistry. Keywords: asymmetric synthesis; catalyst recycling; heterogenisation; organocatalysis; solid support; Introduction Organocatalysts are small molecules that do not contain a metal atom in the reaction centre and are able to increase the speed of reactions. They have proven

• MacMillan were awarded the Nobel Prize in 2021 for the development of asymmetric organocatalysis [6]. To date, industrial companies have used a number of asymmetric organocatalytic processes to synthesise pharmaceuticals and fine chemicals on large scales [7]. Catalyst recycling is key from both an economic

• , giving easily recyclable asymmetric catalysts. The asymmetric sites can be different types, commonly they are binaphthyl-, biphenyl- [91][92][93] and proline-based [94][95]. COFs are a type of crystalline porous material, consisting of covalently linked organic ligands [96][97]. Since the framework only

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• feature of the method is the regioselectivity with asymmetric diketones. In addition to β-ketoesters, acetylacetone can be used in the concept. The same research group employed ethyl 4,4,4-trifluoroacetoacetate as a substrate in this method. The pyrazoline oxidation proved to be critical, and the addition

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• KOH using TBAB as a suitable phase transfer catalyst in a biphasic medium at room temperature. The scalability of the reaction has also been demonstrated. Our future efforts will involve performing an asymmetric version of this reaction using chiral phase-transfer catalysts and the results will be