Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• this conjecture, the present reaction is proposed to involve reversible complexation between the alkyne and the cationic iodine(III) electrophile and subsequent trans-addition of the azole nucleophile, the latter step being coupled with concomitant deprotonation of the N–H bond by the triflate anion

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• isotope labeling experiments [6], followed by a 2,7-cyclization, afforded C6 cationic intermediate IM-3 with cyclopiane skeleton. Quench of the cation IM-3 with water would give 4, while upon two 1,2-alkyl shifts of IM-3, followed by deprotonation of cation IM-4, would give spiroviolene (1). On the other

• IM-7. A key 1,3-hydride shift of IM-7 from the β-face, followed by deprotonation of the formed C2-cation IM-8, would deliver the originally proposed structure 1' [6]. However, no related natural products that would be derived from the intermediates of this pathway have been found so far. A third

• ][20], and fusaterpenol (8, GJ1012E) [17]. A similar 1,2-alkyl shift of IM-10, followed by deprotonation of the formed spirocyclic cation IM-12, afforded 3. Although previous isotope labeling experiments did not support this pathway for spiroviolene cyclization, it should be noted that a subtle

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• metabolic enzymes. In addition, it has been shown to irreversibly inhibit isocitrate lyase 1 (ICL1) from Mycobacterium tuberculosis [40], and key metabolic protein for these pathogens [41]. Isocitrate lyases convert isocitrate to glyoxylate and succinate. Deprotonation of 3NP (pKa = 9.0) results in the

• transition analog of carboxylate groups, resulting in nitro compounds also acting as tight-binding reversible inhibitors [42]. Deprotonation of NNG also results in formation of the corresponding nitronate, albeit with a pKa of 6.6 [24], far lower than that for 3-NP (Scheme 2). Therefore, a much larger

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

• led to the production of preterretonin A (7) (Figure 2) [9]. These data indicated that Trt1 protonates the epoxide of (10'R)-epoxyfarnesyl-DMOA-3,5-methyl ester (6), leading to the cyclization of the terpenoid moiety in the chair–chair conformation, and catalyzes the deprotonation of H-9' of the

• 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

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

• -membered cycle in the latter case. The main direction of the reaction in these examples becomes isomerization (migration of a proton when it is captured by an intermediate anion) or other side processes. In the conjugated anion formed as a result of deprotonation (Scheme 8), one would also expect

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

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• fluorination of 1a–i affords monofluoro products 2a–i in their keto tautomeric forms. For difluorodiketones 3a–i to be formed, enolization of 2a–i-keto must occur through deprotonation at the 2-position, and this process is a key limiting factor [17]. The challenge posed by enolization of 2a–i-keto may be

• pKa(MeCN) of 1a-keto is ≈26.3, and we expect a pKa(MeCN) of 2a-keto to be similar in value [51][52], we suggest fluoride ion may be sufficiently basic to cause significant acceleration of the deprotonation of 2a–i-keto and allow formation of 2a–i-enolates, which then react rapidly with fluorine gas

• as an effective base for the formation of enolates of 1a and 2a, and this is reflected in the modest levels of formation of 3a (Scheme 4). Chloride ion, on the other hand, is less basic (pKa(MeCN) of HCl is 10.30 [60]), however, its greater solubility seemingly allows some level of deprotonation of

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• (Table 1, entries 14–16). The decisive influence of the base for this reaction is probably due to a concerted metalation–deprotonation mechanism [27][28][29][30]. Then, the scope of the Pd-catalyzed direct arylation for access to fluoranthenes was investigated (Scheme 2). The first step of the catalytic

• cycle involves the oxidative addition of 1,8-dibromonaphthalene. Then, a concerted metalation–deprotonation of the arene, which usually occurs at the ortho-position of an activating group such as a fluorine or a chlorine atom, followed by reductive elimination, gives the corresponding intermediate 1

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• deprotonation of 21 to provide radical intermediate 22 [45]. Finally, the iridium excited state (*IrIII) formed under blue light irradiation oxidizes 22 to form product 23 and the corresponding reduced IrII complex, beginning a new photocatalytic cycle. Photocatalytic oxidative quenching mechanism The

• . Decarboxylative fragmentation of 86 forms radical 9, which upon radical addition to 84 and deprotonation yields radical 87. Finally, oxidation of 87 mediated by 85 delivers the Minisci addition product 84 while regenerating PPh3 and NaI (Scheme 16B). The Ohmiya group has developed a series of light-mediated

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• that omitting the photocatalyst led to an even higher yield (Table 1, entry 2), but light irradiation was essential to the reaction (Table 1, entries 3 and 4). Initially, some bases were added into the reaction system considering a deprotonation process, but subsequent investigations indicated that

• formed radical 7 can be oxidized by 2a or 4 giving a cation 8, which undergoes a deprotonation process and formation of the desired product. Conclusion In conclusion, we have developed a visible-light-promoted protocol for the synthesis of dihydropyrido[1,2-a]indolones bearing a trifluoromethyl group at

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• could potentially after deprotonation be reacted with electrophiles as previously established [29] for the parent structure [30] without tert-butyl substituents. UV–vis absorption spectroscopy UV–vis absorption spectra of the known compound 4 [14] and new compounds 9–12 and 15 are depicted in Figure 3

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• , deprotonation of the phenol moiety by the methoxide gives the final product E (2a when acrylonitrile is used as the Michael acceptor). In this case, the proton at the α-position to the electron-withdrawing group is stemming from the protic solvent. Performing the reaction with methanol-d4 leads to incorporation

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

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• deprotonation of acrylonitriles 1 to form anion 1′. The subsequent formal cycloaddition of anion 1′ with azides 2 then affords triazolines 5, which aromatize through a 1,3-H-shift to afford the triazoles 6. Two pathways towards the isomeric triazoles 3 can be proposed: the first involving the electrocyclic ring

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• presence of the NHC derived from the IL deprotonation. Conclusion In conclusion, in this work we demonstrated the possibility to carry out the hydration of alkynes in imidazolium ILs, as alternative solvents until now still little explored for this reaction, employing the Lewis acid BF3 as catalyst. The

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• NHC·CS2 zwitterions relies on the deprotonation of an azolium salt with a strong base, typically potassium tert-butoxide or potassium bis(trimethylsilyl)amide (also known as potassium hexamethyldisilazide, KHMDS) followed by the addition of carbon disulfide either in one pot or after the isolation of the

• excess to compensate for the possible formation of sodium O-tert-butyl xanthate [72][73][74]. We reasoned that these conditions should favor a quantitative deprotonation of the starting triazolium salts and the concomitant trapping of the free carbenes by CS2 prior to their potential decomposition

• vanishing signal was always the most deshielded singlet in the spectra of the reagents, it was a very convenient probe to monitor the success of the deprotonation step. Concomitantly, the incorporation of CS2 in products 4a–c and 6a–f led to the emergence of an equally characteristic resonance in the 13C

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• concert with sacrificial weak reductants (Figure 1b) [8][9][10][11]. Another approach is to add ambient-stable precursors to reaction mixtures: for example, reducing Wanzlick dimers and related species (Figure 1a, ii) have been formed from precursors through in situ decarboxylation [12] or deprotonation

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• the Ph3P−I• species III, forming the cationic intermediate F. Finally, deprotonation of intermediate F yielded the product 34g. Functional polycyclic compounds, such as indene-containing polycyclic motifs and N-containing polyheterocycles are commonly found in many natural products and pharmaceuticals

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• (helping in the deprotonation of the radical cation BIH•+ formed after the reductive quenching of the PS), but also can actively assist the catalysis, by capturing CO2 [50][51][52]. On the other hand, having three hydroxy groups, TEOA is also considered a proton donor and the formation of metal hydrides is

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

• of the resulting hydrazone: a considerable amount of hdz-NO2 deprotonates immediately upon dilution in the aqueous-rich medium at pH 7.4, affording a deep yellow solution due to phenolate-based absorptions centered at around 440 nm. For this reason, we decided to investigate this deprotonation by

• a hydrazone-involving process, meaning, once again, that it probably involves a transition delocalized throughout the molecule. At pH 8.2, the scenario is very different: due to phenol deprotonation, the spectrum now displays three well-defined bands centered at 281, 331 and 440 nm that can be

• (moving from 307 to 332) and 108 (from 331 to 439) nm in the phenolate form of hdz-NO2, being the higher energy component quite unsusceptible to deprotonation and therefore confirming our assignment as a TMP-involving transition. From the pKa determined for the phenol group of the nitro-substituted

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• ≈ 25.8) [34], facilitates the direct deprotonation of morpholine as opposed to acting as a scavenger base. Due to the significant difference in pKa values between the conjugate acids of morpholine (pKa of the conjugate acid is 8.3) [35] and LiHMDS, we posit that LiHMDS directly deprotonates morpholine

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

• . Intramolecular nucleophilic addition of the phenoxy ring of 12 to the activated C–C triple bond afforded intermediate III, followed by deprotonation to deliver product 13 (Scheme 9). When substrate 12 had an OMe group on the phenoxy ring, ipso sulfenylcyclization, or sulfenylation of the phenoxy ring occurred

• , which underwent a ring expansion and 1,2-sulfur migration and subsequent deprotonation/aromatization to deliver product 16. Another work in the use of AlCl3 for cyclization of N‑arylpropynamides 17 with N‑sulfanylsuccinimides 1 was described by Gao and Zhou et al. (Scheme 12) [51]. Annulation in the

• bond of 51 to give the three-membered ring III. Afterwards, intermediate IV was formed by an intramolecular ring opening of III (path I) and presumably produced IV' by path II, which through deprotonation delivered products 53 and 53' respectively. In the meantime, another Lewis acid-promoted

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• the synthesis and applications of NHC–Cu(I) complexes only. 1 Synthesis of NHC–Cu(I) complexes 1.1 Deprotonation of NHC precursors (in situ) with a base The N-alkylazolium salts 11 upon treatment with a base generate the corresponding NHCs which react with a Cu(I) salt to afford the corresponding NHC

• anionic hybrid NHC, “IMes-acac” consisting of fused diaminocarbene and acetylacetonato units. The latter afforded a series of representative Cu(I) complexes through bidentate coordination (Scheme 16) [30]. 1.2 Deprotonation of NHC-precursors with Cu2O Another important and facile method involves heating

• of the NHC-precursor, i.e. an azolium salt with cuprous oxide using a solvent or under microwave conditions (Scheme 17). Kolychev in 2009 attempted the preparation of NHC–Cu(I) complexes via deprotonation by heating of amidinium salt 53 [(7-Dipp)H][Br] with Cu2O in the presence of sodium acetate in

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

• direct precursor of 23 by deprotonation. Furthermore, four closely related terpene synthase homologs from one clade in the phylogenetic tree were investigated (Figure S37, Supporting Information File 1), including enzymes from S. sclerotialus, S. catenulae, S. ficellus and S. morookaense (Table 1

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

• deprotonation of solketal in DMF followed by the addition of oleyl alcohol tosylate. 9.3 was isolated after the hydrolysis in acidic conditions of the acetal protecting group. The protection of the primary alcohol required a protecting group that can be deprotected without affecting the C=C double bond of the

• - or 3-bromoanisole were also reported) with bromotetradecane in the presence of a copper salt (Figure 10). Then, the deprotection of the phenol function with BBr3 produced 10.2. The deprotonation of the phenol function with NaH in DMF and its reaction with solketal mesylate produced, after the

• ] but to the best of our knowledge, R. Berchtold reported in 1982 the first synthesis in large quantities with a control of the chirality at the sn-2 position (Figure 21) [116]. The synthesis starts from (S)-1,2-isopropylideneglycerol (21.1). The deprotonation of the primary alcohol with sodium amide