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

• imine 6’ (96%), which underwent [2 + 2] cycloaddition with methoxyketene to afford β-lactam derivative 7 (79%) (Scheme 4). Selective replacement of the PhSe group of 7 with a 3-butanonyl group (34%) and the subsequent intramolecular Horner–Emmons reaction successfully led to carbacephem skeleton 8 (96

• quinoxaline synthesis was reported to proceed by irradiation with visible light in the presence of dibenzylamine ((PhCH2)2NH, MeCN, rt, blue LED) [64]. This reaction involves a visible-light-induced single electron transfer (SET) process. An efficient radical cascade cyclization has also been reported, in

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

• difunctionalization led to lower yields (2e,f). The product of rearrangement 2a was oxidized into the sulfoxide and re-engaged under the optimized conditions to afford the compound of bis-rearrangement 2g in a good yield of 49%. This compound is then the result of an iterative rearrangement. Difluorinated sulfoxides

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

• simplify the transmission and efficiency of the communication within the scientific community. This led to the extensive use of the symbol nomenclature for glycans (SNFG) representation that is used in all the tools described below (Figure 3) [11][45]. Numerous computer applications have been developed to

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

• in dilute aqueous solutions [17]. The use of this method led to the formation of particles with an average diameter in the range of 200–350 nm and with a domain structure. Domains of about 40 nm in size, consisting of CMC, were connected to each other by a soft material based on chitosan. Such

• . Titration of CMC with hydrochloric acid, followed by treatment with a mixture of hexamethylene diisocyanide and formalin led to the formation of compact particles with an average diameter of 40–80 nm (Figure 3A). These particles were the main building blocks for the construction of cage-like structures

• increase in the cross-linking density to 20 mol % at the first stage led to the formation of a denser packing of particles at the second stage of the process (Figure 4B). Supposedly, this was due to the large steric repulsion between the particles, which prevented the formation of chains on the surface of

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

• -phenyl-2,4-hexanedione was generated in situ through acid hydrolysis of 1,1,1-trichloro-4-methoxy-6-phenyl-3-hexen-2-ones 71. Subsequent cyclization with hydrazine hydrochloride followed by hydrolysis of the trichloromethyl group led to 73. This intermediate was then reacted with 2,2,2-trifluoroethanol

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

• ). In the next set of experiments, different curcumins were examined while keeping 2a as the model arylidenemalonate (Table 2, entries 9–11). The reaction of p-tolyl and p-bromophenyl analogs of curcumin 1b,c led to the formation of double Michael adducts 3i–j in moderate yields (35–43%) over prolonged

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

• hydrophilicity [6]. This, in turn, affects the interfacial and self-assembly properties of the PS [4][5][6]. The uniquely tuneable properties of these photoswitchable molecules have led to their successful application in areas such as DNA compaction [8], photorheological fluids [9][10] and micellar catalysis [11

• replaced by a pyrazole, which improves several aspects of their performance, including quantitative photoswitching between isomers and significantly enhanced thermal stability of the Z isomer [13][14][15]. This has led to recent reports on the integration of AAPs into surfactants to form systems with

• (10 and 90 wt %), and the samples were heated to 60 °C, whilst stirring until homogenous. Samples were left to cool to room temperature whilst stirring. For the photoisomerisation studies using UV–vis absorbance spectroscopy, samples were irradiated to the PSS in a custom-built LED light box with UV

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

• formation of dimeric side products. Cyclic voltammetry analysis suggested an initial anodic single electron transfer (SET) to radical cation 5, cyclization and deprotonation. Subsequent SET oxidation in solution by 5 led to cation 7. Final deprotonation furnished aromatic cycle 4. In 2022, Zhang et al

• the electrolysis was a four-electron oxidative process. Based on this study, the authors proposed the initial anodic oxidation of hydrazone 44 through the loss of two electrons and one proton to form cation 47. Subsequent nucleophilic addition of the azaarene led to new highly acidic cationic species

• generation of electrophilic thiocyanogen as the initial step. Further reaction with the hydrazone 95 and deprotonation led to hydrazonoyl thiocyanate intermediate 99, which isomerized to the thermodynamically more stable isothiocyanate derivatives 100 through 1,3-shift. The latter underwent spontaneous ring

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

• Allostreptomyces sp. RD068384, including a new congener, allostreptamide [24]. Further investigation of this strain led to the isolation of five new β-alkylpyrroles, designated allostreptopyrroles A–E (1–5) (Figure 1). Results and Discussion The fermentation extract of strain RD068384, cultured in A-3M medium, was

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

• 2a, and 0.5 mmol (5 equiv) of TFA under light irradiation (blue LED: λmax = 448 nm) at 50 °C for 1 h in 1 mL (total volume) of 1,2-DCE] [55] with a flow rate of 3 mL/h (light irradiation time: 20 min in the flow reaction, 1 h in the batch reaction). As shown in Table 1, product 3a was obtained in

• result, extending the premixing time and the light irradiation time (Table 2, entry 2) led to an improved yield; the obtained yield was higher than that of the batch reaction system even when half the amount of AgNTf2 was used with the temperature reduced to 25 °C (flow: 54% vs batch: 48%). Meanwhile

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

• HCFCs, along with new refrigeration systems in the 1930s–1960s, has led to the wide application of these materials in household and commercial refrigeration systems [1][2]. In addition, CFCs have found applications as propellants, foam-blowing agents, cleaning solvents, etc. Although these groups of

• fluorinated materials are non-flammable and have low toxicity, CFCs were found to be destructive to the ozone layer of the stratosphere [1][2] due to high ozone-depleting potential (ODP). This has led to the phasing out of CFCs and the replacement with hydrofluorocarbons (HFCs), which show no significant

• cis-isomer decreases, i.e., the cis-isomer of 1,2-difluoroethylene is thermodynamically favored [47]. Deuteration The stereospecific reaction of (E/Z)-1,2-difluoroethylene with a 1–2 M solution of NaOD in D2O (90–120 °C, 2 d) led to the formation of CDF=CDF with high isotopic purity (Scheme 8) [76][77

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 N1-product with highly similar energy (averaging −16.8 kcal/mol). The N2-s-cis and N2-s-trans TSs leading to the N2-product were higher in energy and led to the higher energy N2 products. The critical difference between N1-s-cis and N2-s-cis is the presence of the N2–Cs+–O non-covalent interaction

• for TSs that led to both the N1- and N2-products but lacked any dative preorganization. However, under these reaction conditions, we found that the TS leading to the N2-product, N2-s-cis, was lower in energy than its N1-analog, N1-s-trans, by 1.1 kcal/mol (see Figure 8). This energy difference appears

A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• . Furthermore, the reaction with 4-(acetylamino)benzenethiol led to the selective formation of the disubstituted compound 3c in 53% yield. Phenols are less nucleophilic than thiols and, depending on the substitution pattern, a stronger base is often required to generate the corresponding alkoxide, which is the

• contrast to the reaction with pyridine-4-thiol, which resulted in the S-substituted product 3a, the reaction with 4-hydroxypyridine led exclusively to the formation of the pyridin-4-one-derived compounds 3f and 4f, in 45% and 13% yield, respectively. The substitution occurred at the nitrogen atom rather

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

• conditions in hand, we proceeded with the investigation of the heteroaryl halide scope in batch (Scheme 3). Thiazoles proved to be challenging substrates typically affording the desired products in moderate yields (2b–h). While 2-chlorothiazole led to the production of 2b in 44% yield, 2-bromo-5

• protection of the aromatic NH group (2s vs 2t; 2v vs 2u). Reactions with unprotected imidazoles 1s and 1v led to immediate formation of a precipitate upon addition of the Reformatsky reagent. Surprisingly, 1z did not afford the expected product (2z). The synthesis of the Reformatsky reagent can be combined

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

• - 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

• hexafluoro-2-propanol led to 3-substituted isoquinolinones. The solvent-dependent chemoselective synthesis of isoquinolinone derivatives is interesting and unprecedented. Further research on synthetic utility of PISA, a unique zwitterionic hypervalent iodine(III) reagent, is underway in our laboratory

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

• yield of 83–95%. The second strategy, based on the deacetylation of 29 followed by the GBB-3CR, led to a lower overall yield of 21–23%. The reaction with different 2-aminopyridines and alkyl/aryl isocyanides afforded the intermediates 30 in 86 to 96% yield, and the subsequent deacetylation with

• (IPT)-mediated intramolecular oxidative annulation and a hydroxylamine-induced ring cleavage of intermediate 48. With this one-pot sequential procedure they synthesized 49 in yields up to 95% (Scheme 19). The subsequent GBB-3CR led to the unique 1H-imidazo[1,2-a]imidazole core 50 with 4 distinct

• and the nitrogen atom in imidazoles 65. This interaction increased the steric hindrance around C-2 and allowed the Pictet–Spengler reaction to occur at position of C-4. Indole-4-carbaldehydes were also compatible with this transformation, while indole-2-carbaldehyde (70) surprisingly led to 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

• potent, biologically active compounds. Interestingly, the introduction of a strong methoxy group at position 7 of the 5-aryldeazaalloxazine core led to a bathochromic shift in the absorption spectra of the synthesised molecules, making them more suitable for visible light photocatalysis. Experimental

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

• 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

• three consecutive rings having an angle of 180° between the ring centroids; any angle that is not 180° is considered to be an angular annulation (see Figure 1B). Indeed, although a trend may be observed, it is not nearly as pronounced as the trend we observed for the cc-PBHs in COMPAS-1 [6]. This led us

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

• . Furthermore, the increasing availability of genomic data has led to the development of bioinformatics tools, such as AntiSMASH [3], Bagel4 [4], and RiPPMiner [5], that have emerged to streamline the process of exploring and discovering BGCs in bacteria, known as genome mining. Genome mining has emerged as a

• lanthipeptides produced by these biosynthetic pathways has led to the discovery of many new compounds with potential therapeutic applications during recent years, along with a deeper understanding of their evolution, ecological importance, and gene composition [23]. Lanthipeptides produced by class I and II

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

• , respectively). These findings led us to further optimize the hydroxy-type chiral sulfide catalysts of type (S)-1. Substituting an alkyl group on sulfur of catalyst (S)-1 with isobutyl and tert-butyl [(S)-1b and 1c, respectively] decreased enantioselectivity compared with the n-butyl group-substituted catalyst

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

•  2, entry 3) or at 40 °C for 6 hours (Table 2, entry 4). Finally, reducing the amount of Selectfluor to 1.5 equivalents led to an excellent 90% isolated yield and the conclusion that Selectfluor delivered one electrophilic fluorine (from the N–F) and one nucleophilic fluoride (from the

• ). Dimethyltrifluoroiodane 20 was readily formed under mild reaction conditions using 2.5 equivalents of Selectfluor at 40 °C for 24 hours. However, the introduction of trifluoromethyl groups to the sidearm of the iodine(III) fluoroiodanes led to harsher oxidative fluorination conditions being required because the increased

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

• led to the formation of bisamides 5–8 when other solvents were used, e.g., methanol or acetonitrile. However, the yields of the targeted reaction products in methanol were generally lower than in ethanol, while the procedure in acetonitrile was not suitable for all reagents. It is known that the Ugi

• for two days and then heating the reaction mixture in a closed vessel at 80 °C for 3 hours (Scheme 5). This procedure led to the formation and isolation of the products 10d and 12e with yields which are similar to the tandem reaction. Using the example of bisamide 8c, it was found that changing the

• of acid also led to the formation of amides 10b–d as main products and the corresponding ketobisamides 12d–e as minor products (Table 2, entries 10, 11, 18, 23, and 24). This can be explained by the formation of HCl in the reaction mixture due to the substitution of chlorine in the vinyl chloride

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

• . Heating 5 with hexylamine or aniline in refluxing acetic acid successfully led to the formation of the targeted aromatic diimides bearing either N-hexyl (7-Hex) or N-phenyl (7-Ph) substitutions in good yields. The same strategy was employed to create the imide-capped anthracenes 8-Hex and 8-Ph

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

• . The specific quinones formed were guided by the position of an initial hydroxy group on the polycyclic aromatic hydrocarbon. An available para-position in the PAPs gave p-quinones, while hydroxy groups in the 2- or 3-position led to o-quinones. The substrates were analysed by cyclic voltammetry for

• radical (potassium nitrosodisulfonate) [13] or catalytic systems like methyltrioxorhenium(VII) (MeReO3) [14] and 2-iodobenzenesulfonic acids (IBS)/Oxone® [15] led to either p-quinones or o-quinones, depending on the substituents in the para-position to the hydroxy group. Recently, hypervalent iodine

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

• protecting group yielded the corresponding hydroxyalkynyl derivative 4. Subsequent Lindlar reduction resulted in the (Z)-alkene and a chemoselective tosylation of the primary alcohol led to the formation of tosylate 5. This intermediate underwent a stereospecific 4-exo cyclization upon exposure to iodine

• of 10% Pd/C and 5% Pd/CaCO3 yielded reduced compound 19. Cleavage of the THP group with Amberlist-15® resin and a final Jones oxidation of the primary alcohol to the carboxylic acid, led to cyclization with the 17β-OH group affording the lactone 20 in a moderate overall yield (Scheme 6). Biological

• -toluenesulfonic acid-mediated hydrolysis led to the cyclization reaction yielding the steroidal 17-spiro derivatives. The procedure was applied to synthesize drospirenone (Figure 1) and extended to build the spirolactone 23 from DHEA, a key intermediate toward the popular diuretic spironolactone (Scheme 7). 17