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

• piperidine 17 were obtained in good mass balance under non-electrochemical conditions. Although the detailed mechanism remains an open question, the electrochemical aza-Wacker cyclizations might be radical reactions rather than ionic ones, since the six-membered piperidine was not obtained from the

• . Synthetic outcomes and cyclic voltammetric studies suggest that the reactions are initiated by single-electron oxidation of the alkenes instead of the aryl sulfonamides. Although the detailed mechanism remains an open question, the electrochemical radical cation aza-Wacker cyclizations might be radical

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

• -free conditions at room temperature for 2 h [16]. Although thiamine had already been reported to be effective in other chemical transformations and its role in carbonyl activation in vivo through its thiazole ring is well known, no mechanism of action in the GBB condensation was proposed by the authors

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

• mechanism, see Supporting Information File 1). Such results with previous reports on DMSO acting as a methine source in the synthesis of heterocyclic compounds [35][36] are opening a new avenue for the green synthesis of non-substituted 5-deazaalloxazines in a pseudo MCR fashion. Conclusion In summary, we

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

• domain. The findings of this study provide valuable insights into the effects of lanthipeptides on S. epidermidis, and confirm the previous results acquired during the antimicrobial activity assays. Further studies are needed to confirm the mechanism of action of these lanthipeptides and their molecular

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

• benzodiazepinones, where the protonation would be exclusively controlled by the chiral amine in the synthesis of 6. Moreover, this proposed mechanism also explains the spontaneous cyclization in the absence of a base when 3-bromopropanamine was used (Scheme 8). Moreover, we envisaged the possibility of obtaining

• -phenylglicine. Synthesis of pyrrolopiperazinone 11 using (S)-α-methylbenzylamine. Proposed mechanism in the spontaneous cyclization of Ugi adducts obtained from arylglyoxals and deactivated amines. Synthesis of pyrrolopiperazinoquinazolines 13. Synthesis of piperazinoquinazoline 14. Synthesis of

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

• ]. Studies by Swenton’s [41][53] and Barba’s [54] groups have established that a phenoxonium ion is formed, which is supported by further studies [37][39]. Based on this prior knowledge and our results, a mechanism for the anodic oxidation is proposed in Scheme 3. After two single-electron transfers [38], a

• the hydroxy group is available for oxidation, while o-quinones are formed when the para-position is part of the conserved polyaromatic skeleton. All results are in accordance with an oxidation mechanism going through a phenoxonium cation. Experimental The substrates 1a,b and 6a,b were obtained from

• performed under neutral or weakly basic conditions. Anodic oxidation reported by Swenton et al. [37]. Proposed mechanism for the formation of p-dimethoxy acetals in the anodic oxidation of 1b and 3b. Electrode and electrolyte effects on the electrochemical oxidation of 2-naphthol (1a).a Anodic methoxylation

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

• 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

• –water–NaOAc mixture. Spiro heterocycle 99 was obtained in 52% overall yield as a single product (Scheme 29). The reaction mechanism was elucidated based on the hard and soft acid and base theory. Spiro-1,3,4-thiadiazoline steroids In 2006, Mazoir et al. [56] reported the synthesis of 4α,14α-dimethyl-5α

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

• 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

• processes. The mechanism was initially postulated by Dreiding [30], and supported through isotope-labelling studies conducted by Abe and co-workers [31][32][33]. Subsequently, Cox et al. have elucidated the key enzyme SorbC responsible for the dearomatization process [34][35]. Scheme 4A illustrates the

• families, known as bistetrahydroisoquinoline (THIQ) alkaloids, share a highly functionalized pentacyclic scaffold with different aromatic ring oxidation states and sidechain structures [90][91][92][93]. The biosynthetic mechanism of 5 has been extensively studied by gene disruption and reconstruction of in

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

• ]. Among the different switches known in the literature, azobenzene is a textbook example of a photoswitch operating via a double bond isomerization mechanism, with the first reports of its trans-to-cis interconversion under direct sunlight dating back to the work of Hartley in 1937 [2]. Over the decades

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• decomposition for thiophenylmethanol 3y. Regarding the reaction mechanism, two plausible pathways can be discussed based on literature examples (Scheme 1, path a [17] and path b [33]). In either path, initial ligand exchange to the hydroxy(chloro)iodane I-OH is proposed. For getting an indication of a chloride

• the alkyl hypochlorite IIa. The second mechanism (path b) requires a direct ligand exchange of I-OH with the alcohol and subsequent β-elimination of the alkoxy(hydroxy)iodane IIb to form the desired aldehyde 4. Conclusion In conclusion, this study has successfully introduced N-heterocycle-stabilized

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

• (Mg2+-dependent, metal-independent, cobalamin-dependent), common structural folds (class I–V, with class I being the largest group, characterised by the Rossmann fold) [58], or catalytic mechanism (SN2 mechanism, radical mechanism, Figure 3) [59]. This review categorises RiPP MTs based on the acceptor

• broad range of reactions [60]. There are different rSAM MT classes, description of the classes follows below in the C-MT section. Unlike conventional MTs, which follow an SN2 mechanism, rSAM MTs can methylate non-activated carbons. O-Methyltransferases The predominant group of MTs are O-MTs, which

• binding domain (CBD) at the N-terminus and an rSAM domain at the C-terminus (Figure 9) [119]. In addition to its different enzyme structure, a distinct mechanism of methylation than the classical SN2 mechanism is employed. Reductive cleavage of SAM generates a 5'-deoxyadenosyl (dAdo) radical, which

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• hydrolases and lyases, based on their enzymatic mechanism. ChSase B6 is a chondroitinase originally identified in marine Microbulbifer sp. ALW1 [60] and was cloned and expressed in E. coli. ChSase B6 could digest chondroitin sulfate B into disaccharides with good thermostability and stability against

• fundamentally signaling molecules and enzymatic modification of AQs by Microbulbifer could represent a mechanism of ecological cross-talk among marine microbiomes. Enzymatic halogenation of other signaling molecules, such as that of acyl homoserine lactones, has been postulated to modulate bacterial

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Avenida Francisco J. Múgica S/N 58030, Morelia, Michoacán, México 10.3762/bjoc.20.141 Abstract The reaction mechanism for the chlorination and bromination of 2-naphthol with PIDA or PIFA and AlX3 (X = Cl, Br), previously

• reported by our group, was elucidated via quantum chemical calculations using density functional theory. The chlorination mechanism using PIFA and AlCl3 demonstrated a better experimental and theoretical yield compared to using PIDA. Additionally, the lowest-energy chlorinating species was characterized by

• energy than our proposed species. The reaction mechanisms are described in detail in this work and were found to be in excellent agreement with the experimental yield. These initial results confirmed that our proposed mechanism was energetically favored and therefore more plausible compared to

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• ; however, the generation of 3a was not completely suppressed (Table 1, entry 6). The use of CH2Cl2/2,2,2-trifluoroethanol (TFE) gave similar results (Table 1, entry 7). A plausible mechanism for the reduction of 1a is shown in Scheme 1. First, the reduction of 1a afforded phenylmethanimine (A). Further

• H2 gas, 100 mL min−1; reaction temperature, room temperature; current density, 50 mA cm−2 (10 h). The solution was circulated until the passage of 50 F mol−1. The yields were determined by 1H NMR analysis using 1,1,2,2-tetrachloroethane as an internal standard. Plausible mechanism for the reduction

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

• for the efficient monofluorination of 4- and 2-alkylpyridines (Figure 4 – conditions [A]) [36]. The transformation relied on the polarisation of the heterobenzylic C–H bond, via the intermediate formation of an N-sulphonylpyridinium salt, to promote deprotonation. Following a polar mechanism with

• excess NFSI, the heterobenzyl fluoride is obtained. In the case of product 3, the authors suggested that the absence of radical clock rearrangement products supported a polar mechanism. Conveniently, when both benzylic and heterobenzylic C–H bonds were present in a substrate, the reaction was selective

• selective for primary benzylic fluorination (11) and secondary benzylic fluorination (12) in the presence of tertiary benzylic sites. Although no mechanism has been proposed, the authors concluded it likely proceeded via a radical pathway [23]. In 2017, Baxter and co-workers introduced a silver-catalysed

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• measured by HPLC analysis using a stationary phase chiral column. Synthesis of 3aa on preparative scale. Proposed reaction mechanism. Optimization of reaction conditions.a Supporting Information Supporting Information File 2: Additional optimization studies, characterization data of compounds 3aa–na and

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

• insights we also carried out our standard reaction (Table 1, entry 14) in the presence of well-established radical traps like TEMPO, di-tert-butylhydroxytoluene (BHT), or 1,1-diphenylethene (DPE). In neither case any influence on the yield was observed, thus ruling out a mechanism involving radical species

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

• rather similar Kd values. In order to rationalize this difference in binding mechanism, molecular models were obtained for selected low-energy conformations of E- and Z-isomers of a “model” scaffold of the para-azobenzene derivative in the binding site of LecA (Figure 5), by simple superpositioning of

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

• , based on the syn-elimination mechanism, the ʟ-α-methyl,ʟ-β-hydroxy substrate produced by A2-type KR can also result in a trans (E) double bond [18][22], and some DH domains are reported to have epimerase activity on the α-substitution [23]. Thus, the stereochemical outcomes of KRs in γ- and δ-modules

• either A2- or B2-KRs, but are likely to contain mutations in NADPH binding site [31]. Sequence logo analysis of KRC from γ- and δ-modules In the actinobacterial γ- and δ-modules, the stereochemical outcome of a KR is obscured by further dehydration catalyzed by DH. The dehydration mechanism by DH has

• been investigated in several DH domains, which all follow the syn-elimination mechanism [5][21][33]. Based on the product configuration, we classified DHs into two types, E-type DHs (trans-double bond) and Z-type DHs (cis-double bond) and analyzed sequence logos of the DH-associated KRs. The sequence

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

• compounds 4a–j were also obtained in very good yields (60–98%, Scheme 2). Since the reaction mechanism proceeding with a Wagner–Meerwein rearrangement does not cause racemization or a diastereomeric mixture and preserves the initial enantiomeric excess in the camphene's fluoroalkoxy derivatives (Scheme 4

• mmol), scale-up experiments were conducted. The isolated yield of 4b (1.26 g, 90% yield) is quite satisfactory, as can be seen from Scheme 3. For the fluoroalkoxylation, we propose the mechanism given in Scheme 4. In this mechanism, first the double bond in (+)-camphene attacks the fluorine in the

• alcohol in 2 mL of CH3CN at 90 °C for 2 h. Isolated yields. Scale-up experiments. Reaction conditions: (+)-Camphene (1b) (1.0 g, 7.34 mmol), selectfluor (3.12 g, 8.81 mmol), MeOH (17.62 mmol), CH3CN (20 mL), 90 °C, 2 h. Proposed mechanism for fluoroalkoxylation of (+)-camphene by Wagner–Meerwein

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• by treatment with CH3MgBr in THF [56] (Scheme 4). Based on the previous reports [54][57][58][59], a possible mechanism of this selenocyanation reaction was proposed (Scheme 5). First, the reaction of PhICl2 with KSeCN produces selenocyanogen chloride (Cl–SeCN), which further reacts with selenocyanate

• 3a and their derivatization. Plausible reaction mechanism. Optimization of oxidative thiocyanation of pyrazole.a Supporting Information Supporting Information File 28: Synthetic details and compound characterization data. Funding We acknowledge the National Key Research and Development Program of

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• -position of the o-methoxyphenyl group. Therefore, compound 6g has the same relative configuration to that of the above mentioned product 3a, which also indicated that this reaction has same steric controlling effect. A plausible reaction mechanism is proposed in Scheme 1 to explain the formation of the

• . Molecular structure of compound 4a. Molecular structure of compound 6g. Proposed reaction mechanism. Optimizing reaction conditionsa. The synthesis of the tricyclic compounds 4a–ta. The synthesis of the tricyclic compounds 6a–ka. Supporting Information The crystallographic data of the compounds 4a (CCDC

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

• product of monomer 6. The proposed mechanism is shown in Scheme 2. Anodic oxidation of thioglycoside 6 generated radical cation 11, which was converted to glycosyl triflate 12. 1,6-Anhydrosugar 7 was produced via 4C1-to-1C4 conformational change of the pyran ring to generate cation intermediate 13

• 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

• -anhydrosugar 7. Electrochemical polyglycosylation of monomer 14 with a 2,3-oxazolidinone protecting group. Proposed reaction mechanism of the formation of cyclic trisaccharide 19a. Influence of the functional group in position C-2 on the formation of the cyclic product. Electrochemical polyglycosylation of

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

• content of the reaction environment during the time. Then, to explain the related formation of 5 and 6, we hypothesized a plausible reaction mechanism in which iron is involved in two concomitant catalytic cycles (Scheme 4). Initially, FeCl3 forms an acid–base complex with one of the alkoxy groups of 4

• suitably N-3-functionalized (thio)hydantoins 4a–r. aDCM was utilized as solvent with isothiocyanates 3a–f, while bEtOH was utilized with isocyanates 3g,h. Substrate scope of the iron(III)-catalyzed synthesis of functionalized heterocyclic N,O-aminals 5a–r and hemiaminals 6a–p. Proposed mechanism for the

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

• % enantioselectivity. They employed a double asymmetric induction with (+)/(−)-menthol (12), and CuX2 bis(oxazoline) catalyst where the corresponding chiral mandelate ester 13 was obtained in 81% yield and high selectivity (90% de) (Scheme 6). The proposed mechanism of the reaction is depicted below. Hong et al

• (R1 and R2) were obtained in good to excellent yields witnessing the feasibility of the methodology (Scheme 25). The mechanism depicting the proposed strategy for the Cannizzaro-aldol transformation involves an initial Cannizzaro reaction between paraformaldehyde and the isatin substrate, followed by

• aspects. The application of this highly valuable reaction to the functionalization of bioactive molecules with improved synthetic conditions, will broaden its use in the future. Types and mechanism of the Cannizzaro reaction. Various approaches of the Cannizzaro reaction. Representative molecules