New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• Radovan Sebesta Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia 10.3762/bjoc.21.60 Keywords: asymmetric organocatalysis; covalent activation; noncovalent activation; Organocatalysis is

• organocatalysis. Even toward the end of the 20th century, there have been a few pioneering studies that should be counted as examples of asymmetric organocatalysis. The works of Jacobsen, Miller, Shi, and Denmark et al. marked the early sparks of interest in this type of chemistry based on catalysis by peptides

• prominent Hayashi–Jørgensen catalyst. This prolinol silyl ether was independently discovered by the respective Hayashi and Jørgensen research teams in 2005 [13][14]. Interestingly, the use of prolinol alkyl ethers for asymmetric Michael additions, although at the time added in a stoichiometric manner, has

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• Erlangen-Nürnberg, Nikolaus-Fiebiger Strasse 10, 91058 Erlangen, Germany Department of Chemistry and Pharmacy, Chair of Inorganic and Organometallic Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 1, 91058 Erlangen, Germany 10.3762/bjoc.21.59 Abstract Asymmetric

• enantioselectivity achieved with the calcium catalyst remains modest, mainly due to competing pathways for the Z- and E-hydrazone isomers leading to opposite enantiomers. The experimental results confirm these computational proposals. Keywords: asymmetric synthesis; calcium–BINOL phosphate catalysis; hydrocyanation

• through calcium catalysis [8][9][10]. Asymmetric synthesis has also been achieved via, e.g., 1,4-addition and [3 + 2] cycloaddition of 3-tetrasubstituted oxindoles with a calcium Pybox catalyst [11][12], or through enantioselective Friedel–Crafts and carbonyl–ene reactions [13]. Since the pioneering

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• Abstract The transition-metal-catalyzed asymmetric allylic substitution represents a pivotal methodology in organic synthesis, providing remarkable versatility for complex molecule construction. Particularly, the generation and utilization of chiral secondary alkylcopper species have received considerable

• attention due to their unique properties in stereoselective allylic substitution. This review highlights recent advances in copper-catalyzed asymmetric allylic substitution reactions with chiral secondary alkylcopper species, encompassing several key strategies for their generation: stereospecific

• asymmetric allylic alkylation (AAA) has been remarkable since its initial development in 1995, when Bäckvall and van Koten first reported moderate enantioselectivity using Grignard reagents with allylic acetates [21][22]. This discovery triggered extensive research endeavors, significantly expanding the

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• of its unique interaction in organic synthesis. Chiral halonium salts have been found to have strong halogen-bonding-donor abilities and work as powerful asymmetric catalysts. Recently, we have developed binaphthyl-based chiral halonium salts and applied them in several enantioselective reactions

• , which formed the corresponding products in high to excellent enantioselectivities. In this paper, the asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon stereogenic centers by the Mannich reaction through chiral halonium salt catalysis is presented, which provided the

• corresponding products in excellent yields with up to 86% ee. To the best of our knowledge, the present paper is the first to report the asymmetric construction of β-amino cyanoesters with contiguous tetrasubstituted carbon stereogenic centers by the catalytic Mannich reaction. Keywords: asymmetric catalysis

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• diastereoselectivity at 50 °C (Table 1, entry 16). Finally, the addition of molecular sieves was evaluated (Table 1, entries 17 and 18) affording in both cases lower yields for the reaction product. We also attempted asymmetric reactions using chiral organocatalysts to achieve an enantioselective outcome; however, we

• observed only racemic mixtures, likely due to the occurrence of a background reaction (details for asymmetric trials are provided in Supporting Information File 1). On the view of the results of the optimization process, we decided to study the reaction scope using the reaction conditions of entries 10 and

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• bimanes studied: a) Cl2B (B), representing 90% of the disordered asymmetric unit, b) Me2B, not disordered with dotted line representing an intramolecular hydrogen bond, and c) Me4B showing the majority occupied (55%) N–N moiety. View of the molecular structure in the crystal of a) symmetry generated by

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• olefins with a wide range of nucleophiles, with many organocatalyzed asymmetric examples highlighted in the literature [23][24]. We have observed that the enantioenriched 1,5-dicarbonyl Michael adducts, synthesized via organocatalyzed reaction of cinnamaldehyde with benzyl phenyl ketone, undergo

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• selective substrate and transition-state binding, and for which extensive synthetic development is known [350][351][352][353][354][355]; (iii) they are the lowest possible symmetry polymacrocyclic structure (removing one edge piece will result in a macrocycle) [356][357], meaning ordered asymmetric

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• intermediate in the reaction. When the asymmetric thiosulfonate was used as the substrate, unexpectedly a mixture of three disulfide ethers rather than a single disulfide was obtained under the standard reaction conditions (Scheme 5, reaction 1), which led us to conclude that the reaction might be a process in

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• potential bioactivity [70][71][72][73]. Despite the development of synthetic approaches for six-membered lactams, including transition-metal-catalyzed transformations, several limitations remain, particularly with regard to regioselectivity and asymmetric C–N bond formation, which are still limited. In 2023

• area of medicinal chemistry [93][94][95][96][97]. In 2018, Buchwald and co-workers unveiled the enantioselective synthesis of benzylic amines through the asymmetric Markovnikov hydroamidation of alkenes utilizing diphenylsilane in copper catalysis under mild reaction conditions [98]. Dioxazolones, as

• . Moreover, copper-catalyzed asymmetric C(sp3)–N bond-forming transformations are still underexplored except for elegant studies by the research groups of Buchwald [98] and Chang [74]. Given the versatility and sustainability of the copper-catalyzed transformation of dioxazolones, further investigations for

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

• ][22][23][24]. Moreover, copper-catalyzed asymmetric radical cross-coupling has advanced significantly over the past decade [25][26][27], with notable examples including Liu and Stahl’s enantioselective cyanation of benzylic C–H bonds using a Cu/chiral bisoxazoline catalyst [28], along with the Peters

• ’ and Fu’s asymmetric C–N bond cross-coupling reactions by merging photoredox catalysis with copper catalysis [29][30]. Building on the success of photoredox catalysis, electrochemistry has emerged as a complementary and attractive strategy for promoting sustainability of organic synthesis. By offering

• achieved by precisely controlling the potential. Additionally, the merging of electrochemistry and transition-metal catalysis offers advantages in controlling substrate activation, intermediate reactivity, and bond formation, as well as facilitating asymmetric transformations. As a result, electrochemical

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