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

• investigate hypervalent iodine(V) fluorides has been limited primarily by their difficult preparation traditionally using harsh fluorinating reagents such as trifluoromethyl hypofluorite and bromine trifluoride. Here, we report a mild and efficient route using Selectfluor to deliver hypervalent iodine(V

• ) fluorides by reacting iodine(III) precursors with commercially available Selectfluor. The method avoids large excesses of reagents and pure iodine(V) fluorides are isolated after a simple work-up. Results and Discussion Preparation of bicyclic difluoro(aryl)-λ5-iodanes Two different types of bicyclic

• protocol using TCCA (4 equivalents) and KF (6 equivalents) was then applied to both bicyclic iodine(III) amides 11a and 11b, but these reactions also failed to form either difluoroiodane 7a or 7b. Following the successful preparation and isolation of difluoroiodane 6, we investigated its ability to

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

• bisamides based on the same aldehydes and amines may also demonstrate biological activity. In view of these facts, we decided to develop a new approach for the synthesis of hybrid molecules containing substituted heterocyclic and peptidomimetic moieties. The first stage of this approach was the preparation

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• organic thin-film transistors from heteroacenes. Inspired by these results, we sought to demonstrate the preparation of all-carbon scaffolds, i.e., acenes, that are cata-annulated with cyclic imides. Here, we communicate the successful synthesis of 1,2,3,4-NDIs and -ADIs and the characterization of their

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

• , spanning the period from 2000 to 2023, for the preparation of spiro heterocyclic steroids. The compounds surveyed encompass four-, five-, six-, and seven-membered heterocycles appended to various positions of steroidal backbones, with spirocycles containing oxygen, nitrogen, and sulfur atoms being

• substituents of the new heterocycle rather than functionalization on C-3 (Scheme 22). Spirothiazolidine steroids Horiuchi et al. introduced a novel synthetic approach for the preparation of steroidal spiro 1,3-thiazolidines from 2α-bromo-3-oxo steroids, exemplified by compound 76 [46]. Initially, treatment of

• 2α-bromo-3-oxo-, 2β-bromo-3-oxo-, and 4β-bromo-3-oxo-steroids. In 2012, Shamsuzzaman et al. presented a synthetic route for the preparation of novel steroidal spiro derivatives incorporating three heterocyclic moieties [47]. Initially, thiosemicarbazone 80 served as the starting material, undergoing

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

• biosynthetic intermediate 8 to its analogs 21, enabling the chemo-enzymatic total synthesis of 1. The chemical synthesis commenced with the preparation of two fragments and their subsequent coupling to assemble the core 5/8/5 tricyclic scaffold (Scheme 3A). The left-half fragment, aldehyde 14, was synthesized

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

• . [17], the spectrum of trans-azobenzene can be easily obtained by careful preparation of the sample in the dark. The absorption spectrum of cis-azobenzene, however, is challenging to obtain via direct measurement, due to its intrinsic thermal instability and sensitivity to ambient light. The authors

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

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• report the synthesis of a new series of triazinephosphonate derivatives and their use as dopants in the preparation of new modified Nafion membranes. The triazinephosphonate derivatives were prepared by substitution of chlorine atoms in cyanuric chloride. Diverse conditions were used to obtain the

• , in the same experimental conditions. Results and Discussion Preparation of triazine derivatives The synthesis of 1,3,5-triazinephosphonate (TP) derivatives, to be used as dopants on new membranes, were carried out from the commercially available cyanuric chloride (1), through the substitution of

• to chlorine, and the singlet signal of the phosphorus atom at the 31P NMR spectrum. The synthesis of the corresponding 4-hydroxyphenylphosphonate derivatives followed the same strategy of the amino counterparts’ preparation (Scheme 6). The initial reaction between cyanuric acid (1) and diethyl 4

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• string. Furthermore, we adjust the shell radius from 5 to 6, improving the performance of the ML model to predict pKa values as detailed in Supporting Information File 1, section “The descriptor”. Data preparation and hyperparameter optimization Building on the procedure outlined by Ree et al. [14], we

• preparation and hyperparameter optimization”, the QM-computed pKa values are translated into binary values, with ‘1’ representing the lowest QM-computed pKa value and ‘0’ representing other QM-computed pKa values. The performance metrics for the test set demonstrate that the regression model (MCC of 0.97

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• country. The authors thank Mr. Oleksandr Liashuk and Dr. Anastasiia Hurieva for their help with manuscript preparation, Prof. Dr. Anrdiy A. Tolmachev for his encouragement and support, and all the brave people of Ukraine for making this publication possible. Funding The work was funded by Enamine Ltd. and

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• source (380–800 nm, 300 W) positioned at a distance of 1 cm from the sample. Preparation of aqueous samples All aqueous solutions of DAn were prepared according to the following general procedure: DAn (5.0 wt %) was mixed with 1.0 equivalent NaOH in Milli-Q water. The obtained aqueous solution was

• microscope. The preparation of soft scaffolds composed of DA6, DA7, and DA11, respectively, on a glass substrate was done as follows: Aqueous solutions of DA6 (5.0 wt %, 92.9 mM), DA7 (5.0 wt %, 90.5 mM), and DA11 (5.0 wt %, 82.2 mM) were manually added to an aqueous solution of CaCl2 (150 mM) by pipette

• wavelength of the X-ray beam (Cu Kα irradiation, 1.54 Å). The sample-to-detector distance was ≈100 mm. The obtained diffraction patterns were integrated along the Debye–Scherrer ring to afford 1D intensity data using the Rigaku 2DP software. Attachment of hBM-MSCs onto DAn scaffold surface The preparation of

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• -methylquinoline derivatives could be fluorinated in yields of up to 70%. In 2013, Groves and co-workers reported the use of manganese salen and manganese porphyrin catalysts in the preparation of a range of secondary benzyl fluorides via C–H fluorination (Figure 31) [80]. Substrates bearing electron-withdrawing

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• by harsh reaction conditions, which reduces functional group compatibility and product diversity. As such, the development of practical methods for the preparation of alkylnitriles from readily available starting materials are particularly valuable in synthetic and medicinal applications [15][16][17

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• , deepening our understanding of the stereocontrol of PKSs. Results and Discussion Preparation of KR sequence dataset We first curated the amino acid sequences of KR domains from characterized bacterial cis-AT PKSs recorded in MIBiG database [20] and by manual literature review. In total, 1,762 KRs whose

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• Lu Li Na Li Xiao-Tian Mo Ming-Wei Yuan Lin Jiang Ming-Long Yuan National and Local Joint Engineering Research Center for Green Preparation Technology of Biobased Materials; School of Chemistry and Environment, Yunnan Minzu University, Kunming, China 10.3762/bjoc.20.130 Abstract A catalyst- and

• are not always readily accessible. Typically, the preparation methods involve SNAr reactions with N-centered nucleophiles [5], nitroarene reduction [6] and transition metal (e.g., Pd, Cu)-catalyzed C–N cross coupling of aryl halides, aryl sulfonates or arylboronic acid reagents with ammonia or NH

• anilines [19] (Scheme 1, (3)). To date, although plentiful amination–aromatization approaches for the preparation of anilines have been well-established, to develop novel and efficient synthetic methods still remains highly desirable. In continuation of our recent studies on synthetic applications of

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• polymerization of organic molecules is an important strategy for the preparation of functional materials, such as conducting polymers [1][2][3][4][5]. Electrochemical reactions can be controlled by electric potential or current, electrodes, and electrolytes, which are not available in conventional chemical

• reaction time and rate is possible under electrochemical conditions [11][12][13]. We have been interested in the preparation of cyclic oligosaccharides under electrochemical conditions and electrochemical conversion of linear oligosaccharides of glucosamine into the corresponding cyclic oligosaccharides by

• rate: 7.5 mL/min, recycle numbers: 3) to obtain pure cyclic oligosaccharide 16 (0.125 mmol, 79.7 mg, 62%). Preparation of cyclic oligoglucosamines a) via intramolecular glycosylation and b) via polyglycosylation and intramolecular glycosylation. Proposed reaction mechanism of the formation of 1,6

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• preparation by using small building blocks and that lead, through appropriate transformations, to a product that becomes a substrate for another complexity-generating reaction, merit investigation [13][14][15]. Herein, we report a 3-CR-based synthesis of new properly decorated (thio)hydantoin framework able

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• synthesis of medicinally useful molecules (Scheme 23) [90]. The Cannizzaro reaction has also been applied to the preparation of mandelic acid-based synthons, which gain potential importance in the synthesis of prostaglandins, cephalosporins, and homatropine [65][66][67][68][69]. Synthesis of useful

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• preparation of the Grignard reagent followed by the homo-coupling reaction. Various conditions were examined and biphenyl (3b) was obtained in 85% yield in a one-pot reaction, when bromobenzene (5b) was treated with 1.5 equiv of Mg (turnings, grade for Grignard reaction) under reflux conditions of THF for 24

• , since the preparation of Grignard reagents derived from haloarenes with Mg in situ requires heating for a long time, we decided to use heating conditions for the one-pot homo-coupling reaction. Most homo-coupling products were obtained in this reaction, although the product yield decreased when using

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

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

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• participation of hydrazones attract special attention. This reaction is a general method for the preparation of 1,2,3-triazoles bearing various substituents at position 2. Wherein, depending on the type of starting heterocycles various functional derivatives are formed. So, the well-known Boulton–Katritzky

• undergo base-promoted Boulton–Katritzky rearrangement to appropriate 1,2,3-triazoles 4 (Scheme 1c). Based on the performed investigation a general approach to the preparation of corresponding terarylenes with a 3-hydroxy-4-pyranone unit was designed. Results and Discussion The starting ketones 1 were

• hydrazones. Further, the obtained hydrazones undergo Boulton–Katritzky recyclization to the corresponding 1,2,3-triazoles. Based on the performed study a convenient approach for the preparation of 1,2,3-triazole derivatives with 3-hydroxypyran-4-one unit was designed. It was shown that the proposed method

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• preparation of compound 2a are given in Table S2 (Supporting Information File 1). As can be seen from the table, most of these methods use toxic and volatile organic solvents, and the duration of the associated intramolecular exo-[4 + 2] reaction is quite long. In the scope of this study, the structures and

• reactions, which are a useful strategy for the preparation of many natural compounds and various organic intermediates, can be safely carried out under more environmentally friendly conditions. Experimental All reagents and solvents were purchased from Merck (Merck, Darmstadt, Germany), Sigma-Aldrich (St

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• trimethylchlorosilane. A direct preparation of 6a by reaction of dianion 7 with trimethylchlorosilane is not possible, because the silylation occurs at the terminal carbon atom of the dianion. (2,4-Dioxobutylidene)phosphorane 8 also represents a synthetic equivalent of dianion 7 [23]. However, reactions of such

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• , competent cell preparation, and transformation were performed as described previously [42]. Protein expression and purification The alpG gene was amplified by PCR from S. ambofaciens ΔΔalpW genomic DNA using primers 5’-ggaattccatATGGAAGGGACAACGGCGGACAC-3’ and 5’-cccaagcttTCAGCGGGCGGGGCCGAA-3’, digested with

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• ][8][9][10][11][12]. The interest in the preparation of functionalized indanone derivatives has increased enormously, and many synthetic methods have been developed, including Friedel–Crafts cyclization reactions [13], cyclization of acetylenic derivatives [14], ring contractions and ring expansions

• ], Reformatsky reaction [65], azalactone synthesis [66], nitro reduction [67][68], epoxide rearrangement, thiourea guanylation, and others [69][70]. In this article, we describe a simple and direct protocol for the preparation of indanones through a classical Nazarov reaction catalyzed by bismuth(III) triflate

• . In addition to the synthetic simplicity, the moisture stability of bismuth triflate allows the protocol to be carried out under ambient atmospheric conditions. Results and Discussion Preparation of β-ketoesters We initiated our studies with the preparation of the β-ketoesters, which were synthesized

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• medium). Then, the α- or β-anomer of salt 21 was converted to 2-cyanoethoxy derivative 22 using 3-hydroxypropionitrile and TBTU. This was further transformed into the required phosphoramidite 23 as individual α- or β-anomer, which was used in the preparation of modified DNA sequences on a DNA synthesiser