N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• -(alkyl/arylthio)succinimides 1 led to aryl sulfides 104 (Scheme 43) [77]. The cross-coupling reaction involves protonation of the succinimide moiety by trifluoroacetic acid (TFA) to create electrophilic thio intermediate I. Nucleophilic attack of arene 103 on I led to target product 104. Also, TFA

• , CF3CO2SR, which was produced in the previous step, as a sulfenylating reagent, reacted with I to form the 3,3-bis-sulfide indolenium III. The migration of a sulfide group to the C2-site of indole, generated 2,3-disubstituted indole V. Protonation of V resulted in indolenium intermediate VI. Finally

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• -enones) undergo intramolecular transformation into 3-trichloromethylindan-1-ones (CCl3-indanones) in Brønsted superacid CF3SO3H (triflic acid, TfOH) at 80 °C within 2–10 h in yields up to 92%. Protonation of the carbonyl oxygen of the starting CCl3-enones by TfOH affords the key reactive intermediates

• ][4][5][6][7][8][9][10]). Protonation (or coordination) of basic centers (carbons of unsaturated bonds and heteroatoms) of organic molecules in Brønsted (or Lewis) acids gives rise to not only monocations, but also to highly reactive dicationic (and even higher charged) species. Thus, different

• ). The second protonation of the C=C bond is hampered due to a strong acceptor character of the substituents, contrary to other more donating enones. As a continuation of the research on the electrophilic activation of electron-poor alkenes bearing two electron-withdrawing substituents at the C=C bond

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• either through diphosphate abstraction (for type I terpene synthases) or protonation of the substrate (type II terpene synthases). The resulting cationic species can then react in a cascade reaction via a series of cationic intermediates involving cyclisations, hydride or proton shifts, and skeletal

• in sesquiterpene biosynthesis that can be reactivated by reprotonation for a second cyclisation to eudesmane (6,6-bicyclic) or guaiane (7,5-bicyclic) sesquiterpene hydrocarbons or alcohols, respectively [46][47]. Starting from 26, such a protonation induced cyclisation can lead to C that is the

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• -hexadecyl-2-O-(N-methylcarbamoyl)-sn-glycero-3-phosphocholine, mc-PAF (16.3)). Its synthesis starts with the protonation of lyso-PAF to form 16.2 that subsequently reacted with methylisocyanate to produce mc-PAF 16.3 (Figure 16) [102]. The yield of this reaction was not reported. mc-PAF 16.3, which is

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• upon addition of hydrochloric acid. This is probably due to the protonation of the dimethylamino moiety or/and that dimethylamine hydrochloride is a better leaving group than the free base. The structures of compounds 6a–f were confirmed by 1H and 13C NMR spectroscopy and HRMS, as well as X-ray

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ≈ 8; 50e, 64–74% yield) were suitable, they were unreactive in the presence of a carboxylic acid (50c). If these insertions proceed via initial protonation of the iodonium ylide to produce 51 (Figure 11), its high acidity (pKa ≈ 0) [131][132] would suggest that only strong acids should undergo this

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• ., through protonation and successive reduction or HAT) that upon excitation also acts as a super-reductant (Figure 8C). Simultaneously, Jacobi von Wangelin, Pérez-Ruiz and co-workers introduced the structurally related 9,10-dicyanoanthracene (DCA) as a conPET catalyst. Excitation of PET-generated radical

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• . however, acid 5l underwent partial transformations even under these conditions and was not isolated as individual substance. We assumed the following mechanism for the formation of products 9 (Scheme 8). Redistribution of the electron density in the acid molecule 5 after protonation of the carbonyl group

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• reactivity of catalyst P5 initiated with the protonation of amidates 42 to generate intermediate 44 through ring cleavage. Then, the intermediate 44 was paired with the anionic conjugate base of catalyst P5 and acts as electrophile to facilitate the conjugate Friedel–Crafts reaction involving C3 of indole 4

• pyrroles/indoles 4/9 allowing access to 2,3-dihydroisoxazoles 77/78 bearing an all-substituted stereocenter at the C3 position. A dual catalytic activity of the Brønsted acid catalyst was illustrated by the authors which was initiated with a smooth protonation of the OH group in 76 with a subsequnte

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• by a water molecule to form intermediate B. Further, dehydration and protonation leads to the formation of intermediate E. Nucleophilic attack of amine 36 on E then affords intermediate F. Finally, protonation, cyclization, and dehydration afford N-substituted pyrrole 37. The authors also

• carbonyl carbon to form the 5-membered ring E bearing the iminium ion. Finally, N-substituted amines 67 were obtained after deprotonation/protonation, dehydration, and aromatization steps as shown in Scheme 32b. In another report, Ozaki et al. [87] used the Clauson–Kaas approach to synthesize sulfonic

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• intramolecularly with the C4-pendant prenyl side-chain previously oxidized [76]. Closure of the photoredox catalytic cycle would then involve SET reduction, and protonation would deliver the desired carbocyclic ring (Figure 1c). If this cyclization reaction could be realized in either way, it would shorten the

• to forge the desired six-membered ring through a key C–C bond formation while furnishing secondary radical VI and the undesired seven-membered-ring compound VII. Closure of the photoredox catalytic cycle would then involve either SET reduction of the radical VI and VII (which upon protonation would

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• insertion giving intermediate 16’, which upon protonation gives the desired alkylated product 14. Later, in the year 2018, Yao and co-workers [53] developed the first example of a group 4 metal-based catalyst protocol for the C–H alkylation of pyridine 1 with alkenes 18 and 20 as coupling partners. They

• involves the formation of (dibenzylamido)yttrium complex 28 by the reaction of yttrium complex 26 with HNBn2. Then σ-bond metathesis between the Y–N bond of 28 and the ortho-C–H bond of pyridine gives η2-pyridyl species 29 which on imine insertion produces species 30. Subsequent protonation then provides

• bond of 105 provides a seven-membered rhodacyclic intermediate 106. The protonation at the Rh–C bond of intermediate 106 in the presence of RCOOH furnishes hydroarylation product 104. Nitrogen heterocyclic carbenes (NHCs) are of central importance in organometallic chemistry and in organic synthesis

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• -conjugation of 1,8-bis(dimethylamino)naphthalene (DMAN) fragments through a butadiyne linker and a donor–acceptor aryl–C≡C–DMAN conjugation path. The conjugation path can be “switched” simply by protonation of DMAN fragments. X-ray diffraction, UV–vis spectroscopy and cyclic voltammetry are applied to analyze

• counterpart with an electron-donating methoxy group can be converted into a D–π–A–π–A–π–D system by protonation of the proton sponge fragments (Figure 2). Moreover, oligomers 5 are cross-conjugated π-systems. “A cross-conjugated compound may be defined as a compound possessing three unsaturated groups, two of

• planarization of the naphthalene backbone due to the disappearance of steric and electrostatic stress between the NMe2 groups. The nitrogen atoms in the DMAN fragments strongly approach during protonation and practically do not deviate from the average naphthalene ring plane. The dimethylamino groups naturally

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• composed of TBTQ-C6, as illustrated in Scheme 1. Due to the electrostatic interaction between the host and guest molecules, pH is considered an influential control factor in regulating the assembly and disassembly of supramolecular nanoparticles, as changes in pH affect the protonation degree of the

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

•  44B). In the end, protonation of the Li enolate affords the spiroindane boronate. Due to their paramount role in the fields of bioactive natural products and medicinal chemistry, there is a growing interest in enantioenriched cyclobutanes. Recently, the group of Hall was engaged in developing

• highly beneficial scaffold which was successfully involved in diastereoselective Ni/photoredox dual-catalyzed cross-coupling reactions. Furthermore, rather than the stereoselective protonation, they have also demonstrated the successful trapping of the Cu enolate with benzaldehyde (Scheme 45B). This

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• (established via the α-protonation/deprotonation in the intermediate α-carbanion in the amino acid moiety) and concomitant epimerization of the final product [41]. The results of the thiolation of complex (ΔAlaNi)L7 are given in Table 1. The corresponding ʟ-cysteine derivatives (RCysNi)L7 were isolated in high

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• molecular dynamics (MD) simulations of different protonation forms of Phen-Py-1 and Phen-Py-2 placed in explicit water solvation, and analyzed structural preferences in the obtained trajectories. In setting up our simulations, we prepared the geometries of unionized Phen-Py-1 and Phen-Py-2 and their

• representative geometries that account for most of the population of each system are presented in Figure 2. The results showed that both conjugates, irrespective of their protonation state, prefer stacked conformations, with favorable π–π interactions among aromatic fragments. Interestingly, this also holds even

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• , no significant variations are observed for the bonds N11–N12 and N11–H14, confirming that protonation of N11 is maintained during all the process. In summary, we can define the whole situation as a concerted process taking place in two stages, i.e.: (i) the first one comprises a series of concomitant

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• constants K and apparent equilibrium constants K′ as well as between “chemical” and ”biochemical” reactions. Both chemical and biochemical reactions are carried out at fixed temperature T and pressure p. A chemical reaction involves species (often ionic) in specific protonation states and keeps track of the

• (overall) biochemical reaction involves sums of species that differ only in protonation and, if present, Mg2+ and Ca2+ binding states. It has an equilibrium constant K’, which is referred to as an “apparent equilibrium constant” [10]. A biochemical reaction should be carried out at essentially a constant

• equilibrium. The total ATP concentration is the sum of the concentrations of the individual ionic species formed by the protonation or metal ion binding reactions of the ATP species Additional metal ion complexes (e.g., involving Ca2+, K+, and Na+) can also be included in Equation 4. Similar expressions can

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• intermediate A tetrahydrofuran intermediate B with cis-fused ring systems is formed as seen in the existing literature [7]. A proton transfer of enolate moiety B yields another enolate C followed by the β-alkoxy elimination [17] of intermediate C to form intermediate D. The intermediate D on protonation leads

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• -selinene (10) (Scheme 4A) [43]. Interestingly, while racemic juniper camphor (11) is formed from 1 upon acid treatment [50], this reaction with diluted sulfuric acid in acetone results in (rac)-11 quantitatively. This observation is explained by a protonation-induced cyclisation, successive addition of

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• . This protonation effectively prevents any possible side reactions of the dearomatized products with electrophiles. A remarkably wide substrate scope was observed for this dearomative indole cyclopentannulation reaction, as demonstrated by the smooth ring expansion of the natural alkaloid drug yohimbine

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• , which undergoes a rapid migratory insertion to give intermediate 1-C. The protonation of 1-C produces the intermediate 1-D with the regeneration of the active Rh catalyst for the next catalytic cycle. Under acidic conditions, the further protonation of compound 1-D delivers an imine intermediate 1-E

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• Discussion At first glance, the structure of 2,5-cyclohexadienone 5 suggests a disconnection involving the dearomative addition of 2,4,6-trimethylphenol to α,α’-dimethoxy-γ-pyrone 2 that we eagerly sought to establish under basic activation of the nucleophile or by protonation of 2 (Scheme 2a). This

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• employs an intramolecular proton transfer. We recently showed that a water-mediated concerted deprotonation–protonation is required for the MgMS-mediated cyclization [20]. In order to probe the mechanism underlying the cyclization of 1, we used His6-tagged TadA to carry out in vitro enzymatic reactions

• might adopt a similar strategy as MgMS to initiate C2,6 cyclization though protonation at C2 by bulky water. To obtain further insights into the C2,6-cyclization process of TadA, its three-dimensional (3D) protein structure was constructed with SWISS-MODEL using PaFS (PDB entry 5er8) as the template

• , and the proposed bicyclic neutral intermediate was docked into the active pocket of TadA (Supporting Information File 1, Figure S20). We searched for the amino acid residues surrounding C2 or C3, which might be involved in the C2 protonation, and found the candidate residue Tyr91. In the corresponding