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

• , providing a cost-effective alternative to traditional catalytic methods. The immobilisation of organocatalysts offers the potential to increase catalyst reusability and efficiency in organic reactions. This article reviews the key parameters that influence the effectiveness of immobilised organocatalysts

• methods, such as the application of immobilised organocatalysts [14][15] and heterogeneous organocatalysis [16][17][18], could be a potential driver for the introduction of, for example, enantioselective organocatalysis in the pharmaceutical industry [19]. Knowledge of the factors that influence catalyst

• ]. The role of the polymers as supports for catalysts is not merely passive. These supports significantly influence the reaction environment and catalytic efficiency [42]. Attachment methods, spacer lengths, and polymer nature profoundly impact the catalyst's performance and recyclability. Various

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• understand the conditions for the generation of heteroatom radicals. In addition, from the perspective of recent green chemistry, the development of environmentally friendly synthetic methods is strongly demanded. In other words, a new synthetic method should have excellent atom economy, produce no waste, be

• aware of resource recycling, and promote the use of natural energy [16]. The following three methods are generally used to generate heteroatom radicals (E•) (Scheme 1). In method 1, E• is generated by hydrogen abstraction from E–H by cyanoisopropyl radicals generated by thermal decomposition of 2,2

• on molecular transformations by the reactions of heteroatom radicals with isocyanides using methods 1 and 2. Thus, in this perspective, we mainly focused on the use of method 1 and method 2 for the generation of heteroatom radicals and the reactivity of them with isocyanides. Among these three

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• simulations and analyse the corresponding results. The presented computational toolbox represents a valuable resource for researchers studying protein–glycan interactions and incorporates advanced computational methods for building, visualising and predicting protein/glycan structures, modelling protein

• , especially in bacterial glycans, makes the structural and conformational analysis of glycans extremely difficult, posing a considerable challenge when employing conventional structural biology methods for glycan analysis [10][12]. Nevertheless, understanding the three-dimensional structure of glycans is

• focused in the last decades on the development of new techniques and technologies for the systematic analysis of complex glycans and the study of their interactions with proteins. A multidisciplinary approach, spanning from wet laboratory experiments and biophysical techniques to bioinformatics methods is

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• Colloidosomes are microcapsules built on the basis of colloidal particles [1]. In the past 20 years, many methods have been proposed for the synthesis based on different particle types (inorganic, polymer, and composite) [2][3][4] and shape [5] (spheres, discs, and fibers). A distinctive feature of

• obtain colloidosomes covered with fissures of a controlled size [10]. A simpler method recently proposed involves the self-assembly of starch granules on the surface of emulsion droplets. However, this approach did not allow the pore size to be controlled [14]. Thus, the currently available methods for

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

• numerous other applications. The search for new and efficient syntheses of these heterocycles is therefore highly relevant. The modular concept of multicomponent reactions (MCR) has paved a broad alley to heteroaromatics. The advantages over traditional methods are the broader scope and increased

• intermediates undergo cyclization following a Michael addition to yield the corresponding pyrano[2,3-c]pyrazoles 63 (Scheme 20) [91]. Safaei-Ghomi et al. succeeded in isolating the intermediately formed pyrazole 64 [92]. Since pyrano[2,3-c]pyrazoles are fused heterocycles of interest, catalytic methods for

• ) cycloadditions with alkenes or alkynes to form pyrazoles, also in the sense of MCR. Furthermore, while not strictly classified as pericyclic reactions, hydrazones are also recognized as CN2 building blocks in pyrazole synthesis [169]. 1,3-Dipoles as key intermediates Various methods have been developed for the

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

• appealing opportunities to take advantage of the versatility of this reagent. Such an approach can either ameliorate the previous methods in a more sustainable and efficient fashion or provide a mean for the discovery of new reactivity. Herein, this review aims to give an overview of the state of the art in

• FDA-approved drugs in the United States contain at least one azacycle [33]. Therefore, the development of gentle and efficient methods for accessing these heterocycles is an ongoing pursuit for synthetic chemists. As mentioned above, with their two nitrogen atoms, hydrazones constitute unique synthons

• electrochemical approach constitutes an advantageous alternative to previous methods, which required the preparation of difficult-to-handle hydrazonoyl halides for the synthesis of 1-aryl-5-amino-1,2,4-triazoles from cyanamide [56][57]. Pyrazolines are highly important heterocyclic motifs in pharmaceutical and

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

• claimed to be a potential monomer for the preparation of new fluoropolymers [43][44]. Despite the fact that HFO-1132 has been known for a long time, there are no publications that summarize the chemistry of the compound. With this in mind, the main methods for the preparation of (E/Z)-1,2-difluoroethylene

• synthesis of 1,2-difluoroethylene based on perfluoropropyl vinyl ether as starting material can be found (Scheme 7). Consequently, two methods to prepare 1,2-difluoroethylene in the laboratory have been described to date. Even though at least five approaches to HFO-1132 can be found in patent literature, it

• the methods for the preparation of HFO-1132 as well as reactions demonstrating the chemical behavior of this compound. From the reactions not included in this Review article, mechanistic studies on 1,2-difluoroethylene ozonolysis [77][103][104][105][106][107][108] and studies on the stability of

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• , Parr and Yang developed a now widely used index of nucleophilicity from robust electron population methods such as NBO analyses, referred to as the Fukui index (f-) [44]. The larger the Fukui index, the greater the nucleophilicity, and is thus inversely proportional to the partial charge. Our

• yields from the same carbon sources through reagent control. Experimental General methods All materials were obtained from commercial suppliers and used without further purification unless otherwise noted. Anhydrous solvents were obtained from Sigma-Aldrich and used directly. Reactions involving air- or

• : Characterization of all compounds (1H NMR, 13C NMR, LC–MS, IR), and crystallographic methods and data for products P1 and P2. Supporting Information File 23: DFT methods, relative energy comparisons, TS imaginary frequencies, and XYZ coordinates. Supporting Information File 24: GoodVibes outputs. Acknowledgements

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• ]. The success of this technology ultimately relies on the quality and diversity of the libraries. DEL synthesis must employ DNA-compatible reactions; hence it operates under a limited set of conditions [4][5]. DELs are typically produced via split-and-pool combinatorial chemistry methods. Using

• range of less widely applicable strategies have been developed as well [17][18][19][20][21][22]. The above-mentioned methods focus on the synthesis of α-alkyl-amino acids. Moving to α-aryl-amino acids, the Clayden group published an excellent asymmetric α-arylation method to access quaternary amino

• with the Negishi cross-coupling step in a continuous flow manner [41][42][43]. Continuous flow chemistry offers superior control over reaction parameters compared to traditional batch methods. This approach leads to reproducible reactions, improved safety features, and it can facilitate high-throughput

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• Medicus (Figure 1) [9]. Therefore, in recent years, isoquinolinone derivatives have attracted considerable attention, and successful synthetic methods involving the isoquinolinone framework have been reported. A number of appealing methods for the synthesis of isoquinolinone scaffolds using transition

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• -arylpyridoindazolium salts S1–S3 was confirmed with HRMS and 1H, 13C and 19F NMR data; the complete assignment of the signals was performed using 2D NMR methods. The N–N bond formation was additionally confirmed via comparison of the 1H spectra for the salts and their diarylamine precursors. The absence of the signals

• A1, similarly to the chemical oxidation. The radical cation of dihydrophenazine formed was isolated and studied using ESR and HRMS methods. The ESR spectrum (see Supporting Information File 1) was typical for this type of compounds: a characteristic quintet due to hyperfine splitting on two

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• photochemical reactions under acidic conditions, which were proposed to proceed via radical cations [20]. Since electrochemical and photochemical aza-Wacker cyclizations can offer ring systems that are difficult to construct through state-of-the-art palladium-catalyzed methods, the mechanistic understanding of

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• versatile methods for the preparation of structurally diverse β-lactam derivatives is of great importance and relevance. Continuing the investigation of the reactivity and synthetic potential of diazotetramic acids (1), we have recently shown that these diazo reagents can act as precursors of β-lactam

• (SLC6A19) [10]. Hence, developing new synthetic methods to create structurally diverse 2-oxoazetidine-3-carboxylic acid derivatives is a highly valuable endeavour that could have a positive impact on future drug discovery. Most synthetic approaches to amides and esters of 2-oxoazetidine-3-carboxylic acids

• reported in the literature are based on the construction of the β-lactam ring (Scheme 1). The main methods include the [2 + 2] cycloaddition of acyl ketenes, generated by various methods, with imines [11][12][13][14] and the Wolff rearrangement of γ-amino-α-diazo-β-ketoesters followed by intramolecular

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• achieved during the last five years, and classifies them into five categories: synthetic methods, building blocks, scaffolds, biological activities and physical properties. Keywords: Groebke–Blackburn–Bienaymé reaction; multicomponent reactions; heterocycles; imidazo[1,2-a]pyridines; isocyanides

• future perspectives of this reaction. Review 1 Novel synthetic methods The previously mentioned review, published in 2019 [1], had already highlighted how wide the variety of methods were used to conduct the GBB reaction: as much as 46 different catalytic systems had been reported in the literature at

• (41–67%). Multicomponent polymerizations are simple and efficient methods to construct a library of polymers with great structural complexity and diversity, including fused-heterocyclic polymers[64]. Tang et al. [65] reported the transition-metal-free multicomponent polymerization of dialdehydes 96a–c

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• significant topic. Surprisingly, there has been limited information on 5-deazaalloxazines (dAll) synthesis [20][21][22]. Most known methods employ the cyclization of 6-(arylamino)uracils with one-carbon reagents such as triethyl orthoformate, dimethylformamide dimethylacetal, carbon disulfide, N,N

• -dimethyldichloromethyleniminium chloride and the Vilsmeier reagent, or condensations between o-aminobenzaldehydes and barbituric acid [20][21][23][24][25][26][27]. Neither of these methods allows for the introduction of an aryl substituent into C(5), which confers unique chemical and physical properties on 5-aryldeazaalloxazines

• -type syntheses, MCRs have become helpful tools for more efficient preparation of chemical libraries with higher molecular diversity and complexity in fewer steps and less time [28][29]. Considering the limitations of existing methods, as well as the applications of 5-aryldeazaalloxazines 2, and in the

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• PAS chemical space is with data-driven methods, which have proven in the last few years to be extremely successful at uncovering underlying structure–property relationships. To enable such exploration, we initiated the COMPAS Project (COMputational database of PASs), the first database dedicated to

• PASs and their molecular properties. The first installment, COMPAS-1 [6], contains ~35k cata-condensed polybenzenoid hydrocarbons (cc-PBHs) and has already enabled various directions of investigation, including by training of both interpretable machine [7] and deep learning methods [8], which led to

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• are derived from bacterial natural products (NPs), which have proven to be a valuable source of antimicrobial agents. During the latter part of the 20th century, the discovery of NPs was hindered by the limitation of traditional methods, which often led to the rediscovery of previously identified NPs

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• ; enantioselectivity; halogenation; lactones; organocatalysis; Introduction Catalytic asymmetric halolactonizations of alkenoic acids are powerful methods for the preparation of important chiral lactones in enantioenriched forms [1][2][3][4][5][6][7][8][9][10][11]. A wide variety of chiral catalysts have been applied

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• (PAHs) by cytochrome P450 (CYP) and other metabolic enzymes [7][8]. Main metabolic pathways form quinone isomers of benzo[a]pyrene [8], naphthalene [9][10], and benzene [11]. Numerous methods for the oxidation of phenols or their derivatives to quinones have been described [12]. Oxidation with Fremy’s

• blocked like in 2-naphthol (1a) [17]. Oxidation with iodoxybenzoic acid (IBX) [17] or stabilised IBX (SIBX) [18] form o-quinones selectively, even when the p-quinones are structurally feasible. However, all these methods constitute toxic hazards and/or produce stoichiometric amounts of waste products

• making them less desirable for industrial scale [19]. Electrochemical synthesis methods have a huge potential and this field is currently undergoing a renaissance [20][21][22][23][24]. Replacing chemical oxidants with electric current reduces waste production and gives a sustainable and inherently safe

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

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• Ryo Tanifuji Hiroki Oguri Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan 10.3762/bjoc.20.151 Abstract A steadily increasing number of reports have been published on chemo-enzymatic synthesis methods that integrate

• intermediates from stable and achiral compounds, is complementary to chemical methods and is concise. In addition, adjusting the reaction environment with co-solvents and controlling the selectivity of subsequent dimerization may provide an avenue for the future design and application of more sophisticated

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• εtrans/εcis is the highest, results in the formation of >95% cis-azobenzene [17]. The quantum yields (Φ) of isomerization of this process have been determined using different irradiation wavelengths, solvents, and methods [18][19][20][21][22][23][24]. One of the most interesting properties of azobenzene

• of each isomer, as illustrated by Equation 1. The value for c at the PSS can be found using other spectroscopic methods, such as NMR spectroscopy [17] or the TEM (for Thulstrup, Eggers, and Michl) method [34][35]. With a known value for c, the spectrum of the second component can be found by a simple

• kinetic model describing the components and the non-negativity constraint on the absorbance, can help to guide the decomposition of the data into chemically meaningful concentration traces and species-associated spectra (SAS) [38]. Global and target analysis is one of the methods employed in recent

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• easily overoxidized to carboxylic acids. Over the past decades a variety of methods have been developed, utilizing toxic heavy metals such as pyridinium dichromate (PDC) [3][4][5] or manganese dioxide (Figure 1) [6][7]. Molecular oxygen [8] and peroxides [9][10] can also be used as inexpensive terminal

• oxidants in combination with transition-metal catalysts. Metal-free methods employ chlorodimethylsulfonium compounds as the reactive species and have gained great popularity under the name Swern oxidation or the Corey–Kim oxidation [11]. Hypervalent iodine compounds have also been studied and are well

• optimized conditions, revealing the tetrazole-substituted iodane 1a to be the best oxidant for this reaction (Table 2). The two suitable methods (A: HCl in EtOAc; B: TBACl in MeCN) were then applied to a variety of activated alcohols. The best option is shown in Figure 5. Model substrate 4a could be

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• strain; Introduction Identifying efficient methods for the preparation of densely functionalized molecules is one of the central goals of modern organic chemistry. In this context, application of strained molecules has garnered increasing attention due to their intrinsic reactivity [1][2]. However

• , accessing strained molecules continues to pose a synthetic challenge because many reported methods require harsh conditions for the preparation. An attractive alternative to traditional synthesis can be found in photochemical methods, bypassing energetic constraints by the utilization of photon energy. Thus

• by Norrish–Yang cyclization, which employs easily accessible α-aminoacetophenones as starting materials [11][12][13][14][15]. Furthermore, ring-opening reactions of azetidines have been recently achieved using sulfur and oxygen nucleophiles [16][17][18][19][20][21][22][23][24][25]. However, methods

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• [34]. In reductive amination, the substrate is usually an aldehyde or amine. After the formation of the iminium ion, it is reduced with the appropriate reagent to form the N-methylated amino acid. Different methods have been established using for example benzaldehyde as a protection group, sodium

• cyanoborohydride as a mild reducing agent, and paraformaldehyde as a methylating agent [36]. Methanol can be used as the methylating reagent in other methods. Here, a palladium on carbon (Pd/C) catalyst processes the dehydrogenation of the alcohol to form the corresponding aldehyde. The subsequently formed imine

• -methylation concurrently to peptide synthesis is also possible. Commonly used methods for SPPS of N-methylated peptides involve activating the amino group with 2-nitrobenzenesulfonamide and methylating agents, such as dimethyl sulphate [40][41][42]. Directly methylating peptides is challenging. Multiple amide