Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

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

• bonded to the nitrogen atom of the aniline substrate. The methodology showcases a broad scope for carboxylic acids and demonstrates multiple examples of LSF of pharmaceuticals and natural products. The proposed mechanism begins with the formation of Ru(II) diacetate through ligand exchange between the

• undivided cell using a boron-doped diamond (BDD) anode and a platinum cathode at constant current, resulting in 1,4-dicarbonyls with yields up to 91% and enantiomeric excesses (ee) greater than 99%. This methodology was demonstrated in the LSF of two complex natural product derivatives: a β-ionone

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

• rearrangement reaction [7][8][9][10][14][15]. With the established photo-flow platform and optimized conditions, we were interested in investigating the scope of this methodology using several substituted furfuryl alcohol substrates (2a–p) which were subjected to the Achmatowicz reaction utilizing our photo

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• -diastereoisomer was favored. In this study, enantiopure 3-(1’-(tert-butyldimethylsilyl)ethyl)-β-lactams 10c–f were also tested. Products 12c–f were obtained with moderate to good yield, underscoring the feasibility of the methodology for the C3-substituted β-lactam moiety. The configuration at the newly formed

• thiophenolate. Conclusion To conclude, we have employed a photoredox methodology to access clavam and pyrrolyloxazole intermediates, showing the possibility of using the nucleophilic nitrogen atom of β-lactams under photoredox conditions. The acridinium catalyst IV was able to oxidize the C=C double bond

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• as a key methodology in the synthesis of alkaloids and natural products with 4-, 5- and 6-membered cyclic amine motifs. Initially reliant on stoichiometric reagents, synthetic chemists predominantly used N-substituted chiral imines, organometallic chiral reagents and achiral reagents with an

• almost exclusively produced anti-homoallylamine 7, with (E)-6 being slightly more efficient. This was explained by the reaction switching from the chair-like TS in (E)-crotylation to the boat-like TS in (Z)-crotylation. The developed methodology was successfully applied for the total synthesis of

• as an activator. Interesting examples of a direct asymmetric allylation of indoles 15 (Scheme 4) and 3,4-dihydroisoquinolines 22 (Scheme 5) with geranyl- and prenylboronic acids 14 in the presence of BINOL derivatives were reported by Szabó [25]. In the case of 3-methylindole, the methodology enabled

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

• this research gap by introducing an effective methodology for generating enantiomerically enriched products, thereby expanding the scope of applications and contributing to a deeper understanding of stereoselective covalent catalysis, particularly in the field of mechanochemistry. Results and

• for unconventional reaction pathways by exploiting kinetic energy to surpass equilibrium constraints. This methodology presents several advantages over conventional solvent-based approaches, including the potential for diverse product formation with limited substrates and the development of

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• , Tucson, Arizona, 85721, USA 10.3762/bjoc.20.195 Abstract The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D1]-aldehydes and

• Leuckart–Wallach methodology developed herein, deuterated aldehydes can be converted into [D2]-isocyanides. The optimized conditions for this reaction are summarized below (Table 1). It is important to note that 1 equivalent of formamide and excess [D2]-formic acid (Table 1, entry 2) leads to increased

• modification of 1d, representative of the large swath of chemical space accessible by Ugi-deprotect-cyclize (UDC) methodology, gave the dihydroquinoxaline 1g in good yield with high deuterium retention [29][30][31][32]. The catalytic three-component Ugi reaction was first reported by List in 2008 [33][34] and

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• ) are the key methodology to access valuable heterocycles for medicinal chemistry projects. The classical Biginelli reaction (1893) is an acid-catalyzed, three-component reaction between an aldehyde, β-ketoester, and urea that produces 3,4-dihydropyrimidin-2(1H)-ones, also known as DHPMs (Scheme 1A

• -4,6,7,8-tetrahydro-1H-thiopyrano[3,2-d]pyrimidine-2(3H)-one/thione/selenone 5,5-dioxides and some of their derivatives. Furthermore, this methodology was successfully applied for the synthesis of the SO2-containing analogue of the anticancer drug-candidate enastron (SO2 vs C=O), and we believe a multitude

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

• were overcome by the addition–cyclocondensation of α,β-unsaturated ketones. Embedding 1,3-dipolar cycloadditions into a one-pot process has additionally been developed for concise syntheses of pyrazoles. The MCR strategy also allows for concatenating classical condensation-based methodology with modern

• methodology demands that all sequences have to be performed in the same reaction vessel; neither intermediate work-up, filtration of byproducts, nor solvent exchange by evaporation falls within the scope of MCR. Therefore, this review aims to present and discuss the concepts of ring-forming MCR syntheses of

• necessary [73]. Most advantageously, this methodology tolerates many polar functional groups and allows access to pyrazole libraries from simple starting materials (alkynes, acid chlorides, hydrazines) in good to excellent yield. Notably, pyrazoles 102 and 103 demonstrate intense luminescence both in

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

• , our methodology involves a biphasic reaction medium where the starting material, viz. arylidenemalonate, remains in the organic layer and prevents itself from undergoing saponification because it requires either aqueous or alcoholic (MeOH or EtOH) medium. Furthermore, deprotonation of curcumin

• methodology (Table 2). At first, various arylidenemalonates 2 were tested with a phenyl analog of curcumin 1. The reaction of 1a with arylidene malonates 2a–c, bearing weakly electron-withdrawing para-substituents, produced the corresponding double Michael adducts 3a–c, respectively, in good to high yields

• [26][29]. In order to demonstrate the synthetic utility of our methodology, we performed a scale-up reaction with representative starting materials, viz. 1a and 2b on a 1.0 mmol scale (Scheme 3). The reaction required slightly more time and resulted in the corresponding double and triple Michael

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

• substituents on the aromatic moiety regardless of their electronic properties. However, 4,5-disubstituted 1,2,3-thiadiazoles could not be accessed with this methodology. Mechanistically, control experiments with radical trapping agent such as TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) or 1,1

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• to their populations [25]. The calculated specific rotations −11.4 and +16.1 were obtained for R-configured 2 and 3 from the DFT computations (see DFT methodology section), respectively, which were in good agreement with the experimentally obtained values, −6.1 for 2 and +15 for 3. Thus, R

• monitored by TLC. The solution was diluted with water and extracted with EtOAc three times. The organic layer was washed with brine and evaporated to dryness to afford bismethylated derivative of 1 (1a, 1.9 mg, 88% yield). DFT methodology Prior to the calculations of the molecular properties of compounds 2

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

• Supporting Information File 1). We decided to explore the potential of this methodology for the formation of α-heteroarylacetates. In particular, we were curious to see whether this methodology translates well for five-membered heteroarene substrates (e.g., thiazoles, pyrazoles, imidazoles) which are usually

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

• efficient synthesis of isoquinolinone derivatives using a PISA-mediated methodology that chemoselectively yielded 3- or 4-substituted isoquinolinone derivatives by simply adjusting the solvent. When acetonitrile was used, the 4-substituted isoquinolinone derivatives were the reaction products, whereas

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

• synthesis (DOS) where a single methodology should generate diverse scaffolds. This comprehensive review focuses on all these aspects, and has been divided into five chapters, describing, respectively: a) efforts to develop new and milder reaction conditions; b) the use of new building blocks; c) the

• -aminoimidazole moiety can be found in different alkaloids isolated from sponges and exhibits useful bioactive properties. The methodology employed by the authors to assemble C4/C5-functionalized 2-aminoimidazoles 49 exploited a Mannich condensation followed by an iodoxybenzoic acid (IBX) and N-iodophthalimide

• found to be compatible to the reaction conditions and a gram-scale synthesis was carried out to demonstrate the versatility of this methodology. 3.3 Post functionalization of GBB adducts The structural complexity of the original scaffolds of the GBB adducts can be increased by decorating the structure

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

• Discussion Regarding the synthesis of 5-aryldeazaalloxazines 2 (5-arylpyrimido[4,5-b]quinoline-2,4(1H,3H)-diones), the data in the literature are quite limited, and the known methodology describes the dehydrogenation of initially formed 5,10-dihydro analogues (5-aryl-5,10-dihydropyrimido[4,5-b]quinoline-2,4

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

• properties against S. epidermidis and P. aeruginosa resistant strains and failed to exhibit the same effects against E. coli and C. difficile. As a result, we present the discovery of two new lantibiotics that have demonstrated efficacy in combating both Gram-positive and Gram-negative pathogens. Methodology

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• methodology has several drawbacks, as the need to synthesise the 2-azidobenzoic acid from anthranilic acid and sodium azide, the requirement of anhydrous conditions to perform the Staudinger/aza-Wittig sequence or the generation of large quantities of triphenylphosphine oxide which needs to be removed by

• [29], through post-condensation reactions. Following the methodology previously described in our group [30], the reduction of the nitro group on indole and pyrrole derivatives 9f,g,l–o (Scheme 9, Table 5) employing tin(II) chloride under acidic conditions in boiling n-butanol (120 °C) afforded the

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

• phosphine-based ligand (L). This methodology was applied to the alkynol moiety of ethinylestradiol (8) (86% yield), and alkynols derived from ethisterone, levonorgestrel, lynestrenol, and epiandrosterone (epi-ADT), obtaining excellent yields (85–93%) and high diastereoselectivity (dr > 20:1) in all cases. α

• /mL. Since the cytotoxicity of the parent 16-arylidene steroids was LC50 > 100 µg/mL, it was concluded that the presence of the pyrrolidine moiety was essential for the activity [28]. Additional derivatives have been reported on different steroidal positions [29] or with variations in the methodology

• yields in all cases (Scheme 25). The same methodology was applied to prepare spiro 1,3-thiazolidin-4-one 89, at the C-3 steroidal position from cholest-5-en-3-one (87), yielding an overall yield of 55%. The stereochemical information regarding the new chiral carbons was not provided in any instance. The

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

• combination with an ML model to predict a variety of properties. These properties encompass the site of metabolism [31][33], the strengths of hydrogen bond donors and acceptors [34][35][36], and the regioselectivity of electrophilic aromatic substitution reactions [14]. Building on the methodology from

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

• subsequently attack electrophilic Selectfluor to afford the benzyl fluoride (Figure 2) [34]. The methodology was demonstrated on eight para-substituted benzylic substrates. The authors noted that resubjecting the monofluorinated compound 1 to the same reaction conditions afforded the difluorinated compound 2

• in good yield. The requirement of adjacent to nitro or nitrile groups limits the scope of this approach. Furthermore, the use of strong bases, particularly n-BuLi, prevents the application of this methodology on any substrate bearing sensitive functional groups. An analogous method for

• ; however, the methodology was only shown on secondary benzylic positions. The stereoselective benzylic monofluorination of α-amino acids was also reported by Yu and co-workers, employing a similar directing group strategy (Figure 7) [41]. The use of the monodentate directing group 2,3,5,6-tetrafluoro-4

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• plausible mechanistic understanding at hand, we next investigated the application scope and limitations of this methodology. As outlined in Scheme 3, a series of differently substituted α-azido-β-ketoesters 2 as well as analogous α-azido-β-ketoketones 5 and the α-azido-β-ketoamide 6 could be accessed

• straightforwardly. Furthermore, this procedure was also successfully extended to γ-butyrolactone-based products 7. Unfortunately, this methodology came to its limits when using tetralone-based β-ketoesters like compound 8, which resulted in a complex product mixture, or the acylic β-ketoester 9, which did not show

• any conversion under these conditions. The later limitation shows a clear difference between our methodology and Uyanik’s and Ishihara’s protocol [31], underscoring the higher reactivity of their designer catalyst (Scheme 1B). Having established the TBAI/DBPO-mediated α-azidation using NaN3, we also

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• the o,o’-bis-substituted derivative failed. For the β-S-galactosyl azobenzene derivatives which are accessible by our previously reported Pd-catalyzed cross-coupling methodology between glycosyl thiols and iodoaryl partners [30][38], the required p-, m- or o-iodo-p’-hydroxyazobenzenes 12, 17, and 21

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

• full conversion of 2a under the standard reactions, 1.0 equiv of each substrate was added synchronously. After running 5 times, 65% yield was obtained within a total reaction time of 60 h. Finally, we explored the synthetic versatility of the products in this methodology. Debenzylation of product 4aa

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• selectfluor and a carbocation is formed by bonding with fluorine. Subsequently, fluoroalkoxy compound 4 is formed by Wagner–Meerwein rearrangement followed by alcohol addition and deprotonation. Conclusion New bicyclic fluoroalkoxy compounds were synthesized by a molecular fluorine and metal-free methodology

• distinct advantageous such as (i) the methodology does not require the presence of any metal moities, (ii) enables the synthesis of corresponding oxyfluorinated analogues with high yields and selectivity, (iii) allows derivatization of natural chiral molecules, (iv) uses a safe solvent in mild reaction