Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• 10.3762/bjoc.20.263 Abstract A novel study on the hypervalent iodine-mediated polyfluoroalkylation of sulfoxonium ylides was developed. Sulfoxonium ylides, known for their versatility and stability, are promising substrates for numerous transformations in synthetic chemistry. This report demonstrates the

• versatile intermediates in organic synthesis due to their unique reactivity and ability to participate in a wide range of chemical transformations. In this scenario, sulfoxonium ylides are excellent substrates for bifunctionalization reactions, due to the ambiphilic character in their ylidic carbon [16

• ]. This synthetic potential has been demonstrated in a range of insertions into polar bonds [17][18][19][20], C−H activation transformations [21][22][23], and geminal difunctionalizations [24][25]. Within the literature, a broad array of classical methods describes the synthesis of sulfoxonium ylides [26

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

• years, the Ugi reaction has emerged as a highly considered reaction due to its mild conditions, broad applications, and product diversity. It enables the selective assembly of precursors, facilitating various post-reaction transformations such as deprotection cyclization, 1,3-dipolar cycloaddition, and

• -Ugi transformations, it is possible to obtain diverse heterocyclic compounds with tetrazole moieties [65]. In this context, Medda et al. [66] developed a three-step process to access biologically active imidazotetrazolodiazepinones. The first one is the AU-4CRs among ethyl glyoxalate, amines

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

• a single oligomer across a panoply of different transformations typically range from <1% to ≈30% when n > 1 is desired [35]. To the best of our knowledge, the assembly of functionalized [n]staffanes from 1 in high yield/selectivity and in one step via controlled radical oligomerization remains a

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

• pyrrolidine intermediates A can undergo further transformations (Scheme 10), depending on their structure and the iodane reagent being used. For example, higher yields of 3-fluoropiperidine products 6 were observed when using cyclic iodane reagents 21 and 22 (Scheme 10), which was suggested to be because a

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

• recognition, and supramolecular assemblies [9][10][11][12][13]. There are numerous examples of using metalloporphyrins as artificial photosynthesis models, enzyme mimics, and catalysts for various organic transformations, where a metal center acts as an active site [14][15][16][17]. However, metal-free (or

• 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

• light irradiation. There are a few reports on red light-mediated transformations using other pyrrolic macrocycles, such as thiaporphyrin [94], phthalocyanine [95], and subphthalocyanine [96]. Porphyrin macrocycles can also absorb red light (Q bands at 518, 553, 592, and 648 nm with extinction

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• trifluoroethanol to Et3N for the subsequent catalysis). Thus, this protocol enabled a straightforward and rapid synthesis of highly 2-substituted indoles under mild reaction conditions, highlighting the versatility of propargylamine as a bifunctional reagent in post-Ugi-azide transformations. Our group pioneered

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

• the two transformations. Studies directed toward a better understanding of possible transition-state structures and the design of new catalysts to improve the results are currently underway in our laboratories. A potential energy surface (PES) for the proposed mechanism for (a) isomerization of

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

• of allylic peroxidation 2, 4 and 5 were observed (Scheme 4) [24]. Similar transformations were reported later using CuCl as the catalyst [39]. Later, Gade with coauthors demonstrated the allylic peroxidation of cyclohexane with TBHP using the alkylperoxocobalt(III) complexes [Co(BPI)(OAc)(OO-t-Bu

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• Poznań, Poland 10.3762/bjoc.20.247 Abstract The incorporation of fluorine atoms within the structure of organic compounds is known to exert a significant impact on their electronic properties, thereby modulating their reactivity in diverse chemical transformations. In the context of our investigation

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

• various useful transformations under mild, eco-friendly reaction conditions [4][5][6][7][8][9][10][11]. Various review articles [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and books [27][28] have appeared on the chemistry of hypervalent iodine compounds. In the past two decades

• capability to function as radical initiators. The use of diaryliodonium salts as efficient electrophilic arylating reagents in a wide range of organic transformations is due to their unique features such as solid-state nature, excellent stability, and the presence of a robust leaving group [39][40][41][42

• reductive elimination to produce the desired sulfilimine 99 (Scheme 40) [92]. Synthesizing S-aryl xanthates through transition-metal-catalyzed or SNAr reactions presents challenges due to potential additional transformations occurring under the reaction conditions. However, employing diaryliodonium salts

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• . Various reagents and chemical transformations have been elaborated in this context over the years [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Despite these recent advances, the design of highly functionalized

• various transformations [54][55][56][57][58][59][60][61][62][63][64]. In consequence, a large number of transition-metal-catalyzed or radical-mediated processes for C–H functionalization of aldehyde hydrazones has flourished over the years. An ideal scenario for a direct and sustainable synthetic route

• towards trifluoromethylthiolated hydrazones will be the direct C–H functionalization of the corresponding aldehyde hydrazone, an uncharted transformation to date. Forging a C–S bond by the direct C–H-bond functionalization of hydrazones is still underdeveloped. Except for transformations leading to the

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

• and 1n were studied. Both gave the expected products in yields of 50% (for 3m) and 44% (for 3n). Besides these successful transformations several ketones proved unsuitable (Scheme S1 in Supporting Information File 1). Additionally, attempted [4 + 1]-type cycloadditions of three 1-arylprop-2-en-1-ones

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

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• purification. The synthetic utility of the prepared tetronic acids was demonstrated by further transformations at the hydroxyethylidene fragment. The structures of one obtained tetronic acid and one product of derivatization were confirmed by X-ray analysis. Keywords: allomaltol; base-promoted recyclization

• -hydroxypyran-4-ones these products are widely used in organic synthesis [17][18][19][20][21][22][23]. Among the diverse chemical transformations of allomaltol derivatives the recyclizations of the pyranone ring are of great interest. As a rule, such reactions are realized under action of nitrogen-containing

• nucleophiles and open access to a large array of substituted pyridin-4-ones. Various conditions and reagents employed for these transformations are presented in numerous papers [24][25][26][27][28][29]. Besides that, approaches to the synthesis of pyridazinones and pyrazoles based on the interaction of 3

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

• electrochemical transformations. Detailed reaction conditions, such as electrolyte, electrode material, and the use of constant current or constant voltage, are presented. Additionally, we discuss the mechanisms of some representative reactions and provide selected examples of LSF of relevant bioactive compounds

• arenes via palladium-catalyzed electrooxidation, further showcasing the versatility and potential of this approach in organic synthesis (Scheme 42b) [58]. These methodologies underline the expanding role of palladium catalysis in electrochemical transformations, offering robust strategies for the

• into a carbon radical intermediate. The photocatalyst then oxidizes this intermediate, leading to the final product (Scheme 45). This approach underscores the significant potential of combining electro- and photocatalysis to achieve selective and mild transformations in organic synthesis, particularly

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• transformations, then reaction extraction and separation, into a single process, which are typically performed individually/separately in batch methods. This enhances the overall efficiency for obtaining the desired product(s) from the reaction mixture. In continuation to our efforts on developing flow-based

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

• al. [156]. Moreover, it is unclear whether AAM significantly improves the accuracy of reaction modeling. The AAM-required methods are usually tested on specific reaction types, where the reaction transformations and AAM are clear and correct. However, most large-scale reaction datasets do not have

• related literature, caution is advised as experimental apparatus from different sources could introduce systematic errors in reported yields [46]. Furthermore, BO cannot generalize well from past reactions to unseen reaction transformations, which inherently requires gathering new relevant data for new

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

• finally be reopened by trifluoroacetate (Scheme 3). Although the selenylated compounds 2 are of interest, the presence of the PhSe moiety allows other transformations to be considered. First, the oxidative elimination of the selenyl moiety to generate a double bond was first studied. However, regardless

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• : antioxidant activity; catechol thioethers; heterocycles; redox-transformations; thiones; Introduction Synthetic derivatives of polyphenols, in particular catechol (hydroquinone), represent a promising group of pharmacologically active substances [1][2]. Catechol-containing compounds demonstrate

• [25]. A feature of mercapto-substituted heterocycles is the possibility of their existence in two tautomeric forms: thiol or thione [26][27]. The ability to tautomeric transformations affects their biological activity and allows the use of these molecular blocks to design compounds with different

• (control) during the incubation for 3, 24, and 48 hours (concentration of compounds in the reaction medium is 0.1 mM). The results are expressed as mean ± standard deviation (* p < 0.001; ** p < 0.01; ***p < 0.05). Synthesis of catechol-containing compounds 1–9. Electrochemical transformations of compounds

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• , whether isolated or generated in situ, may undergo various controlled transformations [42]. However, previously, we failed to introduce amino-1,2,5-oxadiazoles bearing an amide functionality into the diazotization protocol, arguably due to an increased electron-withdrawing effect and elevated instability

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

• ][7][8]. Furthermore, the integration of mechanochemistry and organocatalysis leads to the development of more sustainable transformations, characterized by reduced reaction times, decreased catalyst loadings, and significantly diminished solvent usage and waste production [9][10][11]. The pioneering

• studies by Bolm [12][13], and Juaristi et al. [14]. have significantly advanced chiral secondary amine-catalyzed stereoselective reactions under ball milling conditions, representing a widely explored activation mode in mechanochemical-mediated transformations. However, reports on chiral primary iminium

• [15][16] or iminium-ion catalysis [17] under ball-mill conditions are scarce, in contrast to the abundance of transformations catalyzed by such covalent catalysis. Among the numerous organocatalytic reactions facilitated by primary amine-based iminium ions, Michael-type additions deserve special

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

• ), Koser’s reagent (PhI(OH)OTs), Zhdankin’s reagent (C6H4(o-COO)IN3, ABX), and Dess–Martin periodinane (DMP) – and find application in an array of synthetically important transformations including olefin difunctionalization, carbonyl desaturation, alcohol oxidation, and C–H functionalization [3][4

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

• transformations. Subsequently, we review ML employed for privileged catalysts, before focusing on its application for catalyst and reaction design. Concluding, we give our view on current challenges and future directions for this field, drawing inspiration from the application of ML to other scientific domains

• catalysts [3]. In particular, enantioselective organocatalysis has shown an impressive rise in the last decades, owing to the tunability of catalysts and different modes of activation, enabling a manifold of different transformations [4][5]. The development of the field, driven by many researchers, led to

• 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

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• blocks for further transformations. We have focused on the investigation of gem-difluorination of carbon–carbon triple bonds, because this procedure is one of the most simple but powerful and straightforward methods. In addition, there have been a few reports in the literature that seem to mainly rely on

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• cleavage and further transformations. The isomeric altenusinoides A and B (52 and 53) were isolated from Alternaria sp., where no biological activities were determined so far for these compounds [242]. Altenuene and its diastereomers and substituted derivatives Altenuene and its diastereomers: Altenuene