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

• the use of HF or its complexes as a reagent. These reactions seem to proceed via the formation of the vinyl fluoride as the intermediate [25][26][27][28]. In the first example, Olah and co-workers reported the reaction of terminal alkynes with HF/pyridine (Olah reagent) (Figure 1, reaction 1) [29][30

• ][31][32], although the original work was developed by Linn and Plueddeman using HF [33][34][35]. As another example, Renoux and co-workers developed the utility of SbF5/HF (Figure 1, reaction 2) [36]. In 2014, the HF/N,N’-dimethylpropyleneurea (DMPU) complex in the presence of an Au catalyst was found

• HF is still inevitable [40][41]. Quite recently, Crimmin and co-workers reported gem-difluorination by shuttling between fluoroalkanes and alkynes, in which catalytic HF played a key role [42]. In the course of our study on the fluorination reaction, we have envisioned that the combination of a

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• . This is in agreement with results on the co-optimization of PEG with phosphoenolpyruvate, which indicate an optimal concentration of 4% PEG (7.5 kDa) and a decrease in the activity of the CFPS system at concentrations above 5% [47]. PEG-8000 has been shown to have opposite effects on transcription and

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• is straightforward and has broad applicability, extending to other azidated molecules and polymers. Experimental Materials All reagents are purchased from TCI, Aldrich, and Kanto Chemical Co. Inc., and used as received. 4,5-Diiodophthalic acid was prepared according to a literature method [20]. A

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

• both β-keto thioesters and β-keto amides [40][41]. Li and co-authors achieved the synthesis of β-keto thioesters by CF3SO3H-promoted hydrolysis of α-oxo ketene N,S-acetals with an amino leaving group (Scheme 1a, path 8) [40]. Subsequently, using NaOH-promoted hydrolysis of α-oxo ketene N,S-acetals, we

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• diketone 1b, bearing the less electron-withdrawing 1,3,4-oxadiazole moiety (σm/σp 0.335/0.443), with alkylamines proceeded well (73–74% yields), but required the addition of CHCl3 as co-solvent due to the low solubility of the starting 1,3-diketone 1b. On the other hand, the reaction of 1,3-diketone 1b

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• for diverse applications in future studies. Keywords: condensation; co-timerization; dipyrromethane; Friedel–Crafts acylation; heterocycles; pyrrole; truxene; Introduction The scaffold of truxene (10,15‐dihydro‐5H‐diindeno[1,2‐a;1′,2′‐c]fluorene) and its congeners comprises three fluorene subunits

• – sharing a common benzene ring at the centre [1]. The notable structural signatures of truxene are its rigid, planar and C3-symmetric skeleton, wherein three peripheral phenylene ring systems are all meta-positioned with respect to the congested central benzene ring, so that all four benzene rings are co

• functional materials for diverse uses [1][5][6][7]. Notably, to synthesize this vital heptacyclic star‐shaped π‐conjugated polyarene framework, only a single acid-mediated co-trimerization step is required from an inexpensive and commercially available starting material, namely 1-indanone [8]. It is to be

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

• controllability of surface, geometry, and pore size makes silica-based materials sustainable and functionalisable supports for organocatalytic reactions [44]. The particle morphology of mesoporous silica can be tuned to various shapes, including spheres, tubes, and rods of various dimensions [45], by using a co

• lead to a decrease in selectivity. Connon and co-workers have attached a cinchona thiourea organocatalyst to magnetic nanoparticles 13 for the Michael addition of dimethyl malonate (10) to trans-β-nitrostyrene (11) (Scheme 3) [31]. To explore the potential impact of nanoparticles on catalyst efficiency

• conditions (Scheme 4). Thiel and co-workers examined N-benzylthiazolium salts 17 anchored covalently to mesoporous materials in a benzoin condensation reaction (Scheme 5) [65]. Initially good yields were observed, even after a short reaction time, but a drop in yield was seen after reusing the catalysts for

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

• reaction, pressurization in an autoclave or other pressurization device is required to increase the CO concentration. Isocyanides, on the other hand, have an isoelectronic structure with carbon monoxide and are expected to be not only a promising C1 resource but also an important synthetic reagent for

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• strategy to improve or modulate their physicochemical and biological properties [41][42][43][44][45], only few publications have reported a [3,3]-rearrangement with fluorinated molecules (Scheme 1c). In 2020, Wang and co-workers have developed a one-pot [3,3]-sigmatropic rearrangement/Haller–Bauer reaction

• of aryl sulfoxides with difluoroenoxysilanes as nucleophile under mild reaction conditions [46]. This provided access to organosulfur compounds ortho-functionalized by CF2H. At the same time Peng and co-workers described the dearomatization of aryl sulfoxides using the same difluoroenol silyl ether

• (Scheme 1d). It is important to mention that during the preparation of this paper, a similar study appeared. Peng and co-workers demonstrated the efficient use of acetonitrile as nucleophile with various aryl difluoroalkyl sulfoxides but only one example of an SCF3 compound was reported [49]. Results and

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

• search space, can be done by comparing the target protein to related proteins or those co-crystallised with ligands [103] and manually superimposing the new ligand to the reference structure. Some payment software like Glide [116][117], GOLD [118] and Molecular Operating Environment (MOE) dock [119] can

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

• aliphatic alkynes, copper iodide is necessitated as a co-catalyst [141]. In addition to classic Sonogashira catalysts, phosphane-free palladium [Pd(NN)] chelate complexes can also be used, which promote excellent regioselectivity [142]. A variation of the reaction is possible with Mo(CO)6 as a carbon

• palladium-catalyzed oxidative carbonylative Sonogashira alkynylation and cyclocondensation with arylhydrazines [144]. In 2009, Müller and co-workers introduced an alternative approach for synthesizing alkynones through a one-pot process [145]. Azulen-3-ylalkynones 126, obtained by glyoxylation of azulene

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

• -arylidene-1,3-indandiones was reported by Zhang and co-workers using quinine as a catalyst, giving multicyclic spiro-1,3-indandiones in moderate yields with enantioselectivities as well as diastereoselectivities [39]. However, to the best of our knowledge, arylidenemalonates have not been employed as

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• brilliance of synchrotron X-ray sources enables the mechanisms of structural changes in PS to be studied, using in-situ light irradiation with time-resolved data collection. For example, Tribet and co-workers used this approach to explore the kinetics of micellisation and dissolution of cationic Azo-PS, both

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

• catalyst (Pd, Pd, Pt, Rh, Ru, Ir, Ni/Cu, Ag, Au, Zn, Cr, Co, Scheme 5) [62][63]. Further, 1,2-Dichloroethylene was reacted with hydrogen fluoride in the presence of metal fluorides or transition metals (Cr, Al, Co, Mn, Ni, Fe) to form 1,2-difluoroethylene (Scheme 6) [56][58]. In patents [59][60], an exotic

• and co-workers [93]. Therein, a mixture of products, with diethyl 2-chloro-1,2-difluoroethylphosphonate as main compound, was formed (Scheme 15). This mixture was reacted with absolute ethanol, and the esters formed were separated by distillation and characterized. The authors did not point out which

• case was predominant over [2 + 2]-cycloadducts. Reactions involving C–F bonds It was shown by Liu and co-workers that SiF2 was able to insert into the C–F bond of 1,2-difluoroethylene, as well as into the emerging Si–F bond, leading to a mixture of fluoropolysilanes with a low combined yield (Scheme 24

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• ). Histaprodifen 64 is a potent H1 receptor agonist with a 3,3-diphenylpropyl moiety at position 2 of the imidazole ring characterized by Elz and co-workers [58]. The authors showed parent compound 64 and methylated derivatives 65 and 66 were potent H1 receptor agonists in pithed and anaesthetized rats (Scheme 11

• , Menghin and co-workers [61] explored flexible chain incorporations at the terminal nitrogen of histaprodifen generating hits 79–86 (Scheme 11). Finally, the N,N-bis(2-imidazolyl)ethyl)-substituted amine superhistaprodifen 87 cluster was exhaustively synthesized and tested for their agonist activity

• against chloroquine-sensitive and resistant Plasmodium falciparium strains in mice were reported by Jain and co-workers [65]. Initially, these authors developed simple halohistidine derivatives as first generation analogues showing successful in vitro antimalarial activity. Prompted by these findings, a

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

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

• , including one super-cluster containing two co-localized operons from Clostridium cellulovorans 743B, that encode for two new peptides named clostrisin and cellulosin. Each operon was heterologously expressed in Escherichia coli. Molecular weights associated with the expected post-translational modifications

• was co-expressed with the corresponding precursor peptide in the same E. coli strain (expected size 150 kDa). The precursor peptides and the peptidase domain of CloPt1 were fused with a 6xHis tag at their N-terminal end for purification purposes (Figure S7 in Supporting Information File 1). After

• predictions suggesting that this should be a functional system. This lack of modification could be due to the amino acid sequence of the precursor, which differs from those described in the literature, or to mutations in the CloM1 enzyme. These mutations may require additional co-factors or specific

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• multiple extractions into hexane under a nitrogen atmosphere in a glovebox. A similar synthetic approach to acyclic iodine(V) fluorides was developed more recently by Ismalaj and co-workers by reacting iodoarenes with 6 equivalents of KF and ex situ-generated chlorine gas within a two-chamber reactor setup

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• acid hydrolysis. Similar results were obtained by Dömling and co-workers [27], who used 2-nitrobenzyl isocyanide as a universal convertible isocyanide, and the amide group was also converted into a carboxylic acid under the conditions of acid hydrolysis (Scheme 2). Therefore, taking into account the

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

• dimers, which indicates a radical intermediate [36]. Swenton and co-workers [37] established evidence for the phenoxonium ion (Scheme 1), and were further able to divert the reaction into forming ortho-oxidation due to steric hindrance (Scheme 2). Cyclic voltammetry studies of the oxidation of 2-naphthol

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

• final CO insertion to release the ester. After an acid hydrolysis which produced 36, a basic treatment induced the condensation reaction to yield the heterocycle 37 in 99% yield. This reaction sequence was also applied to the acetates of ethisterone and ethynylestradiol, resulting in similar yields in

• yields (82–85%) (Scheme 28). The authors proposed a free radical mechanism facilitated by hydrogen peroxide, generating a primary radical at the terminal nitrogen atom -CO-HN• which then adds to the carbon atom of the imino group. The reaction mechanism was substantiated by theoretical calculations

• . According to the mechanism, the heterocyclic ring closes by the attack of the bulky radical -CO-HN• over the α steroidal side to circumvent the 1,3-diaxial interaction with the methyl group at C-10. Spiro-1,3,4-oxadiazoline steroid Shamsuzzaman et al. achieved the synthesis of 5’-acetamido-3’-acetyl-(3R

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

• pathway of brassicicenes in Pseudocercospora fijiensis is outlined based on an investigation by Oikawa and co-workers [23]. The biosynthesis begins with the conversion of farnesyl pyrophosphate (FPP) and isopentenyl pyrophosphate (IPP) to geranylgeranyl pyrophosphate (GGPP), catalyzed by the

• I (9). As a pioneering investigation to elucidate the mechanism of this essentially identical allylic oxidations by Fe(II)/2OG-dependent dioxygenase, Dairi and co-workers conducted in vitro enzymatic conversions with the homologous enzyme Bsc9, derived from Alternaria brassicicola ATCC96836 [24

• , and subsequent reduction of the exomethylene at C11–C18 catalyzed by BscH yield brassicicene O (12). Renata and co-workers successfully accomplished the chemoenzymatic total syntheses of cotylenol (1) and nine brassicicenes (Scheme 3) [19]. In the cyclization phase, a suitably functionalized 5/8/5

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

• solar cell detectors now being commercially available at a reasonable cost, instructions for building laboratory apparatus for quantum yield determination using direct measurement of photon flux using solar cell detectors have been reported by Riedle and co-workers [44][45]. With the design reported by

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

• ) as a co-product, which strongly inhibits various MTs [16][17][18][19]. To overcome these limitations, numerous in situ SAM supply and SAM regeneration systems have been developed [4][20][21][22][23][24][25][26], thereby enabling preparative biocatalytic scale methylation reactions [27]. Such

• biocatalytic applications. The co-crystallisation of LahSB with bound SAH provides important details about the structure–function relationship, the substrate–enzyme interaction, and the cofactor binding site (Figure 5). This structural information, including the residues involved in binding, is essential for

• cyclised core peptide to exert its effects on the precursor peptide. Furthermore, SAM was shown to be an obligate co-substrate for OlvSA [71]. Crystallographic data of OlvSA is not yet available. The predicted three-dimensional structure displays substantial differences from the crystal structure of LahSB