Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• there are many reasons for this renewed interest, two major motivations are the unmatched control of oxidation or reduction potential that can be achieved and the environmentally friendly aspect of having electrons as the only consumed reagent. This latter reason is certainly an advantage in many cases

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

• latter conditions to the reaction with benzylamine, the target substituted aniline 3aa was formed in a good 73% yield. However, the reaction with less nucleophilic aniline was sluggish, requiring almost 15 days to achieve full conversion of the 1,3-diketone 1a (TLC control). In this case, performing the

• reaction of 1,3-diketones 1e and 1f with aliphatic amines was expected. Indeed, the reaction of 1,3-diketones 1e or 1f with benzylamine was sluggish, and a number of undefined side-products were formed (LC control). m-Isoxazole arylamine 3ea was isolated in low yield (21%) after heating for 6 days (Scheme

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

• the catalyst enhanced the mass transport of organic reactants in water [122]. Based on similar mesoporous catalysts [123][124], it can be concluded that with a properly designed pore size resulting in a high density of active catalytic sites, diffusion control could be diminished. Furthermore, the

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

• ] because isocyanide is susceptible to multiple imidoylation [9][10][11], whereas carbon monoxide is less susceptible to multiple carbonylation. Therefore, precise control of the reaction is required for selective formation of the monoimidoylation product. Regarding the radical reaction of isocyanides, the

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

• obtaining cage-like structures are characterized by technical complexity, a multi-stage nature, and low yield of target structures. To develop a one-step method for the synthesis of cage-like structures, it is necessary to control the deposition process of colloidal particles on the surface of emulsion

• a narrow pH value range. This allowed to control the process of cage-like-structure formation. Changing the conditions of the Ugi reaction made it possible to obtain various structures, including cage- and cap-like structures, as well as hollow microspheres. Due to the developed surface, these

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

• spatiotemporal control. To build responsive materials, surfactants are particularly attractive due to their ability to self-assemble into different morphologies depending on their molecular structure and chemical environment. To that end, photoswitchable chromophores can be incorporated into amphiphilic

• is only with this additional care that there can be confidence in the structural determination of photoswitchable materials using X-ray radiation. This understanding is vital as the field advances to harness the improved properties of new photoswitches with greater isomerisation control, such as

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

• 30. Importantly, a control experiment using benzaldehyde-derived N-benzoylhydrazone delivered the corresponding 1,3,4-oxadiazole in only 25% yield. This result indicates that benzaldehyde-derived hydrazone is a less probable reaction intermediate, thereby supporting the proposed mechanism (Scheme 7

• 38. As such, the iodide electrolyte served as an electromediator to both promote the decarboxylation process and protect the aniline product from overoxidation. Importantly, a control experiment without electricity but in the presence of molecular iodine instead proceeded smoothly, thereby confirming

• situ cathodic generation of the base was supported by a control experiment in a divided cell, where no conversion was achieved. Final formal (3 + 2)-cycloaddition with the dipolarophiles 73 delivered the pyrazolines 74. It is interesting to note that a complementary (3 + 2)-cycloaddition between

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

• cytotoxicity against Kasumi-1 human acute myeloblastic leukemia cells with IC50 values of 103, 105, and 105 while 2 and 3 were less active with IC50 values of 200 and 333 μM, respectively. Under the same experimental conditions, cisplatin, a positive control, inhibited the cell growth with an IC50 value of 70

• μM. Compounds 1–5 were merely inhibitory against tyrosinase, showing 19, 13, 9.6, 18, and 15% inhibition at 200 μM, respectively, while a positive control, kojic acid, inhibited the same enzyme by 95%. Conclusion In summary, five new alkylpyrroles, allostreptopyrroles A–E (1–5), were discovered from

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• scale-up, are the advantages of using a flow system. In addition, reproducibility in a liquid–liquid flow system is improved because the flow velocity and temperature can be precisely controlled by using a syringe pump and a temperature control unit, respectively. Moreover, as the reaction mixture

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

• the presence of Cs2CO3. To explore the possibility of N2-selectivity, we hypothesized that the phosphine intermediate of a Mitsunobu reaction could provide chelation control, directing alkylation to the indazole N2-atom while using identical alcohols as described above. Thus, we subjected 6 to simple

• 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

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

• 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

• control plant diseases but also have some herbicidal activity. Compound I showed good inhibitory activity against Sclerotinia sclerotiorum on detached oilseed rape leaves [8], and compound II has excellent herbicidal activity against dicot weeds, such as Zinnia elegans Jacq. and Abutilon theophrasti

• - or 4-substituted isoquinolinone derivatives with excellent chemoselectivity. These interesting findings led us to investigate the reaction mechanism. To gain insight into the mechanism and chemoselectivity of the reactions above, we performed a control experiment. With acetonitrile as the solvent, a

• aforementioned control experiment and literature precedents, we proposed a mechanism for the formation of 4-substituted isoquinolinone derivatives, including 2a. The reaction begins by tautomerization of 1a, and PISA undergoes an electrophilic reaction with 1a' to form the iodane intermediate A. The iodane A

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

• representative radical cation precursors that are widely used to realize the formation of unique bonds. The respective radical cations are trapped by various nucleophiles under radical and/or ion control, where kinetic and/or thermodynamic effects are expected to be dominant. Typical examples that clearly show

• mmol), Bu4NOTf (0.1 M), TFA (1 equiv), CH3CN (0.4 mL), and 1,2-DCE (3.6 mL). Yields reported here are isolated yields. Mechanistic studies of aza-Wacker cyclization. A: Electrochemical (Bu4NOTf in CH3CN/1,2-DCE), B: non-electrochemical (LiClO4 in CH3NO2). Control studies for electrochemical aza-Wacker

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

• -substituted products 60 underwent TFA-promoted deprotection which triggered the intramolecular cyclization to furnish the indole moiety in the desired products 61. A control experiment showed that the GBB product 60 was obtained as the sole product in the absence of acid catalyst. Another group developed the

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

• the benzene ring of the 5-deazaalloxazine core at 7.64 and 7.71 ppm. To support this theory, we conducted a control experiment between 3,4-dimethoxyaniline (3b) and N,N-dimethylbarbituric acid (5) in DMSO. To our delight, 5-deazaalloxazine 6 was formed (Scheme 2B). To prove that DMSO was the methylene

• . aReaction was done in DMF/AlCl3. bIsolation requires precipitation with 2-propanol. c2 days. Control experiments related to bulky substituted aldehydes. Optimization of the reaction conditions for the synthesis of 2a. Supporting Information Supporting Information File 28: Spectroscopic and analytical data

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

• producing strains were not distinct from the control ones, transformed with the empty vector. As a result, it was not surprising that there was no effect on the E. coli test strains, which confirmed previous observations. For S. epidermidis MIQ43, P. aeruginosa ATCC PA14, and MIQPA25, both clostrisin and

• cellulosin samples displayed robust bacteriostatic activity at the highest estimated concentration of 5.6 µg/mL and 4.8 µg/mL, respectively, compared to the bacteria grown in LB media (control), and lower but statistically significant effects at lower concentrations (Figure 5). The immature peptides CloA1

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

• control of the current [32][33][34]. Early studies on the electrochemical oxidation of phenols revealed that the oxidation passes through a phenoxonium ion and forms acetals in methanol but quinones in the presence of water [35][36][37]. However, the reaction is sometimes accompanied by the formation of

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

• bioassays against multi-drug resistant parasite Plasmodium yoelii in Swiss mice revealed that pregnane-based trioxanes 161b were the most active compounds, showing 100% suppression of parasitemia on day 4 at 48 mg/kg × 4 days, a similar activity to that of β-arteether used as positive control. Bis

• Plasmodium falciparum chloroquine-resistant W2 clone, whereas N-propylamides showed better activity against the D6 clone. Among them, compound 167c had the best activity (IC50 = 9.29 nM against the D6 clone), almost as good as artemisinin (IC50 = 8.6 nM) used as control. Tetraoxanes were also screened for

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

• synthesized 33 generated the highly reactive intermediate 34 in aqueous solvents under mild conditions [37][42]. In this process, the co-solvent (cs) allowed control of the dimerization modes via either Michael addition or Diels–Alder reactions, facilitating the systematic total synthesis of the

• experimental results, Gulder and co-workers devised a strategy to control the dimerization modes by adjusting the polarity of the organic co-solvent to establish the divergent synthesis of dimeric scaffolds. Indeed, with 20% DMF in the SorbC-catalyzed enzymatic oxidative dearomatization, the Michael addition

• tolerance through enzyme mutagenesis should allow more precise control over scaffold-constructing reactions. As with the related natural products, hybrid sorbicillinoids were also known to be biosynthesized through Diels–Alder reactions between diene 34 and non-sorbicillinoid-derived dienophiles [29

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

• (Avantes IC-DB26-RM), which allows the proprietary software AvaSoft from Avantes to control the internal shutter of the light source via a PC. With this configuration, starting a single measurement in AvaSoft sends a TTL signal to the light source that opens the shutter, which is followed by the

• acquisition of a spectrum, and finally a TTL signal is sent to close the shutter again. By utilizing scripts we developed (see Supporting Information File 1), it is possible to precisely control the timing of irradiation of the sample with the LED and the perpendicular illumination with the UV–vis probe. In

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

• ). The corresponding protecting group (PG) was thought to control the conformation of the 1,4-biradical 2, which is known to be important for efficient Norrish–Yang cyclizations [27][28]. Furthermore, the PG was deemed crucial for the development of further functionalizations of the azetidinols (vide

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

• , ions, and heat [15][16][17][18][19][20][21][22]. Light enables noninvasive stimulation with high spatial and temporal precision to control structural transformations of supramolecular assemblies in organic and aqueous media [19][23][24][25]. Various photochromic and photoresponsive moieties, such as

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• conformational stability of proline-rich proteins such as collagen [2]. Therefore, pyrrolidine derivatives are particularly susceptible to conformational control induced by a fluorine substituent. The 5-membered pyrrolidine ring is a cyclic alkylamine that adopts a conformation that resembles the familiar

• fluorine gauche effects to evaluate significant conformational biases in all of the possible isomers. Achieving conformational control upon the introduction of a second fluorine atom in fluoropyrrolidine presents challenges. Unlike the chair-like conformation of six-membered rings, five-membered rings lack

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

• and oxidation potentials. Electrochemical methods Synthetic electrochemistry is a powerful tool offering excellent control over reaction kinetics and selectivity [86]. Electrochemical oxidation has been demonstrated as an efficient means for generating benzylic cations, allowing for the introduction

• -oxidation and decomposition to improve the reaction efficiency overall. Conclusion The fluorination of benzylic C(sp3)–H bonds provides rapid access to an important functional group used in medicinal chemistry to control the pharmacokinetic profile of drug candidates. Historical and recent research efforts

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

• peroxide catalyzed by tetrabutylammonium iodide (TBAI). By utilizing these readily available bulk chemicals a variety of cyclic β-ketocarbonyl derivatives can be efficiently α-azidated under operationally simple conditions. Control experiments support a mechanistic scenario involving in situ formation of

• -yielding conditions for the synthesis of 2a, we next carried out a series of control experiments in order to address the role of the catalyst’s counter anion and the oxidant (Table 2). Running the reaction of 1a and NaN3 in the presence of stoichiometric amounts of Bu4NI3, I2, Bu4NIO3, or Bu4NIO4 did not

• the presence of a catalytic amount of tetrabutylammonium iodide (TBAI). Control experiments support a mechanistic scenario proceeding via in situ formation of a catalytically competent quaternary ammonium hypoiodite first. This higher oxidation state species then facilitates the α-iodination of the