Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• activated by the base, affording the active amido complex Mn1-a which reacts with the alcohol to form the alkoxo-type complex Mn1-b. An intramolecular ligand-assisted mechanism produced the aldehyde and manganese hydride complex Mn1-c after protonation of the intermediate. The aldehyde then underwent aldol

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• observed that the β-anomer of charge-neutral nucleoside Vb exhibited similar inhibition of hCDA as the control dZ (IIc). Presence of a negative charge in nucleoside Va led to lack of inhibition at pH 7.4. We assumed that protonation of Va might result in some inhibition of hCDA. However, the pKa of Va was

• against hCDA (Table 1), which might be a result of protonation of the pyrimidine ring in dZ (IIc). Some inhibition of hCDA by the β-anomer of Va was observed at pH 4.7, with a Ki value of 560 μM. At this pH value, less than 1 in 1,000 molecules of Va might be protonated, which could mean that protonated

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• products) were found to be somehow unstable when concentrated to dryness during work-up. We hypothesize that a possible cause of such instability might consist in the formation of a highly electrophilic iminium ion upon protonation of the hemiaminal ether by silica or glassware acidity and further

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• provide a better overall understanding. The hydrochlorination of alkenes can be categorized into three main classes (Scheme 1; only a terminal alkene is shown as a substrate, although polysubstituted and conjugated alkenes can also serve as substrates). 1) Polar reactions: These involve the protonation of

• alkene reactivity is essential. Two reactivity scales for alkenes are available in the literature, one considering the reactivity of the alkene itself (Mayr scale) [25] and the other the stability of the corresponding cation after protonation (hydride affinities) [26]. In the polar hydrochlorination

• reaction, the protonation of the alkene is the rate-determining step. This process can be viewed as the reaction between a nucleophile (alkene) and an electrophile (proton). According to the Mayr–Patz equation log(k) = s(N + E), the second order reaction rate constant k at 20 °C for a reaction is related

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• easily converted into hydrophilic charged entities by the protonation of the unsubstituted amino functionalities in their structure providing improved bioconjugation. Spectroscopic data All porphyrin conjugates were structurally characterized by IR, UV–vis, NMR spectroscopy, and mass spectrometry. The IR

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• meroterpenoids: insuetusin A1 (12) and insuetusin B1 (10), respectively (Figure 2) [9]. Like other Trt1-type enzymes, InsB2 catalyzes the protonation of the epoxide, the formation of two six-membered rings in a chair–chair conformation, but the reaction finishes with the deprotonation of the hydroxy group at C-3

• to produce compound 10. In contrast, InsA7 commonly initiates and terminates the reaction with the protonation of the epoxide and the deprotonation of OH-3, respectively, but it produces product 12 via a boat–chair conformation. Since all of the other Trt1-like cyclases catalyze the reaction with

• cyclization process is initiated by the protonation of the epoxide, leading to the formation of a cation at C-7. A cascade of migrations then occurs to form the final backbone: H-6 migrates to the cation C-7, the methyl group at C-13 shifts to C-6, H-10 migrates to C-11, and finally, deprotonation of the

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• summarized in Scheme 8). The first pathway is realized in the formation of five-membered (in the case of 3-bromopropanol) and six-membered (in the case of 2-(bromomethyl)benzyl alcohol) cycles – the cyclization of the anion is faster than its reverse protonation. The same applies to substrates with activated

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• and drug delivery systems [12]. pH-Responsive molecular tweezers A particular case of coordination-responsive systems is when a proton is used as a stimulus leading to pH-responsive systems with the protonation/deprotonation of the switchable moiety. The conformational switch in these systems is

• signals in the low-range visible/NIR region. Upon protonation of the pyridine, the conformation switch leads to a spatial separation of the active Pt moieties and a release of the guest (Figure 4). Also, the same group demonstrated the induction of chirality and fluorescence with chiral guest molecules

• observed confirming the formation of the host–guest complex. Again, protonation of the pyridine results in a guest release and a loss of the CD signal. Thus, this system provides a peculiar example of the control of chirality by a pH stimulus. A similar moiety employed for acid–base-triggered

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• concerted attack and protonation [59]) may be being mimicked by the gold-catalyzed processes here, further supporting the viability of a mechanism like that shown in Scheme 2. Finally, at its extreme, increasing nitrogen basicity inhibits gold catalytic activity, but within this low basicity regime, the

• behaves accordingly here [66]. Specific gold–oxygen interactions are typically not invoked in mechanistic discussions, though a gold alcohol complex has been proposed in silyl enol ether protonation [67]. Equilibrium studies by Maier et al. indicate that methanol is more weakly coordinating than alkynes

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• . The difference between the two mechanistic pathways is the nature of activation of the carbonyl group. Protic acids induce the protonation of the carbonyl group of the aldehyde or ketone, enhancing its electrophilic character. Whereas, Lewis acid catalysts bind to the heteroatom of the carbonyl group

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• , protonation, and luminescence, have recently been studied by us in sufficient detail [15], nothing is known so far about the possibility of chemical modification of this molecule. It should be emphasized that the presence of a dimethylene moiety in the peri-positions of the naphthalene system will not only

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• mechanism of the CPA-catalyzed transfer hydrogenation reaction was proposed (Figure 2). The activation of 3,3-difluoro-substituted 3H-indole 1 by protonation through the Brønsted acid generates the iminium A. Subsequent hydrogen transfer from the Hantzsch ester gives the chiral amine 2 and pyridinium salt B

Facile access to pyridinium-based bent aromatic amphiphiles: nonionic surface modification of nanocarbons in water

• Lorenzo Catti,
• Shinji Aoyama and
• Michito Yoshizawa

Beilstein J. Org. Chem. 2024, 20, 32–40, doi:10.3762/bjoc.20.5

• through the template effect of the hydrophobic nanocarbon guests (Table 2). Moreover, aromatic micelle (PA-Im)n and its host–guest composite (PA-Im)n·(C60)m were anticipated to provide pH-dependent ZPs via imidazole-based protonation/deprotonation. Micelle (PA-Im)n showed a significantly higher ZP (41.7

• mV) compared to the other derivatives in neutral water, owing to the basic imidazole groups (Table 1). The protonation behavior of the imidazole groups on (PA-Im)n·(C60)m in D2O (0.5 mM based on PA-Im) was monitored by 1H NMR spectroscopy, showing significant down-field shifts of the imidazole ring

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• azomethine nitrogen N1 as H-acceptor is observed, which originates six-membered cyclic motifs with a graph-set (6) [39]. The hydrogen atom is closer to O1 than to N1, indicating that the preferred protonation site is the former, as can be observed at the Fourier difference maps (Figure S1A and S1B in

• absorptions lose intensity by around 10% along the first 48 hours after dilution in buffer (Figure S13 in Supporting Information File 1). The mechanism associated with the hydrolysis of N-acylhydrazones involves the protonation of the azomethine nitrogen (in this case, N1), followed by the nucleophilic attack

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• alternative approach towards crown ether–porphyrin hybrids. They have introduced the crown ether segment by exploiting a dicarbinol 38, which, once subjected to the reaction with pyrrole, formed 39 [68]. The latter reacted with arylaldehydes under acidic conditions yielding 40 (Scheme 11). Protonation of 40

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