Synthesis of sterically shielded piperidine nitroxides via acid-catalyzed heterocyclization of β-aminoketone derivatives with ketones

• Mark M. Gulman,
• Yurii I. Glazachev and
• Sergey A. Dobrynin

Beilstein J. Org. Chem. 2026, 22, 948–954, doi:10.3762/bjoc.22.74

• , generated by deprotonation of acetylene, propargyl alcohol, or N-Boc-protected propargylamine with ethylmagnesium bromide, whereas nitrone 6b was treated with allylmagnesium bromide. Subsequent quenching of the reaction mixtures with water, followed by oxidation with MnO2, afforded the corresponding

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• suitable ligands such as N-heterocyclic carbenes or electron-rich phosphines, the deprotonation of an N–H heteroaromatic can generate a copper–amido intermediate [32][33][34]. These species typically exhibit enhanced nucleophilicity and can engage alkenes via the direct nucleophilic addition of a copper

• been widely explored. Among the various catalytic systems, copper catalysts have attracted particular attention owing to their ability to activate amine components by forming copper–amido species. In this activation mode, deprotonation of the N–H bond generates a Cu–N intermediate with enhanced

• , particularly for ester-substituted alkenes. Mechanistic insights obtained from the DFT calculations suggested that the reaction proceeded via a copper–amido catalytic cycle involving metal-assisted olefin activation and the aminocupration pathway. In the initial step, deprotonation of the amine by KOt-Bu

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• carbon–metal species (Scheme 1a). Fagnou and co-workers reported direct arylation reactions with palladium(II) acetate to synthesize biaryl compounds via concerted metalation–deprotonation (CMD; Scheme 1b) [25][26][27]. Buchwald, Hartwig, and co-workers explored carbon–nitrogen coupling reactions that

• concerted metalation-deprotonation (CMD) process, a carbon–palladium bond is formed to give the palladacycle intermediate Int-4. Next, reductive elimination between the quinoline and arene moieties forms the C–C bond to give intermediate Int-1 and regenerates the palladium(0) catalyst. Another oxidative

Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• passes through relatively low barrier (ΔG# = 24.7 kcal/mol), yielding intermediate I. Deprotonation of the latter leads to ketene J, which via rotation across single bond (intermediate K) can cyclize to carbene L. An intramolecular H-shift to the carbene center in L leads to the final pyrrole 5. Further

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• deprotonation [29] of [(P^N^C)AuH]+ by water, to give a T-shaped Au(I) intermediate, (P^N^C)Au, capable of sequestering the alkyne. This in turn is attacked by another Au(III) hydride to complete the anti-addition process (Scheme 13) [69]. Ligand effects of C^N, C^P and P^N chelates Gold(III) complexes of C^N

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• density distribution between the C2 and C4 positions following deprotonation. An aryl group located at the α-position (C2) greater facilitates the resulting negative charge delocalization, thereby reducing electron density at C2 relative to C4. Consequently, this stabilized carbanion directs the formation

• derivatives 54 from readily available optically pure amino acids without any external chiral additives [4] (Scheme 24). Deprotonation and coordination of optically active imines 52, obtained from various natural or synthetic α-amino acids, such as ʟ-alanine, ʟ-tryptophan, ʟ-aspartic acid, ʟ-glutamic acid, ʟ

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• deprotonation of the acid; indeed, their coordination to the copper center must also be taken into account [45]. Moreover, the reaction between FA and amines occurs in a more complex manner than a common acid–base equilibrium. In fact, calorimetric studies on the formation of FA/triethylamine adducts showed

Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• lyophilization, the product 2a was obtained as fully protonated TFA salt (43%); deprotonation with equimolar aq. NaOH produced the sodium salt of 2a quantitatively. The analytical characterization of 2a turned out to be difficult, because even in DMSO-d6, most NMR signals remained very broad, and in part

• threonine, complementary to the cationic surface patch on survivin. B) Click coupling (i) between the H3-T3ph peptide with C-terminal 5-azidoornithine 3 and butynyl tweezer 4a with subsequent deprotonation (ii) to the sodium salt of peptide tweezer 2a. Binding peptide yellow, ornithine grey, butynyl group

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• from Scheme 26 and Scheme 27 were coupled via Corey–Chaykovsky reaction and the so-obtained epoxide was treated with m-CPBA yielding sulfone 251 as the major diastereomer (Scheme 28). Regioselective deprotonation and epoxide opening with in situ-formed Ti(III)-species from Cp2TiCl2 and zinc led to the

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• deprotonation. The coordination of the hydroxamic acid groups to the uranyl cation stabilizes the deprotonated hydroxamate form, effectively lowering the apparent pKa and enabling strong binding even at low pH [33]. It is important to mention that the formation of the stable 5-membered chelate between the

• uranyl ion and the Z-isomer of hydroxamic acid effectively shifts the Z/E equilibrium [70] towards the Z-conformation through a metal-induced fit mechanism [71][72]. Consistent with known hydroxamate coordination chemistry, coordination-induced deprotonation of the hydroxamic acid at low pH provides the

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• = 0.735 V vs Fc/Fc+ in CH2Cl2) is oxidized more readily than the 2-naphthol partners (Eox of 4a = 1.081 V and Eox of 4b = 1.286 V vs Fc/Fc+ in CH2Cl2). The radical cation [3]·+ then undergoes rapid deprotonation to form a neutral radical intermediate (Int-I) with high spin density at the reactive site

• , enabling regioselective intermolecular coupling with 4. While a Scholl-type coupling-first scenario cannot be ruled out, the computed acidity of [3]·+ (pKa ≈ −5.2) together with the more spin-density localization in Int-I supports a deprotonation-first, neutral-radical pathway, consistent with related

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• 1), addition of water affords adduct M, which subsequently converts to the ester via deprotonation. In dry solvents (path 2), nucleophilic attack by the departing OSO₂F− anion on L produces intermediate N, containing an S–O bond that is ultimately cleaved under basic conditions to yield the ester

• -transfer (SET)-driven mechanism. Coordination of the arylamine to the potassium cation followed by deprotonation generates potassium amide salt AB. A SET process forms amine radical AC, which then transfers an electron to the amide, generating radical anion AD. Coupling of AC and AD forms a tetrahedral

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• -closure to the cation 20a, followed by a sequence of hydride (20b) and proton shifts to cation 20c, and a second hydride shift to 20d. Subsequent cyclobutane formation via 20e and a ring expansion furnishes cation 20f, which is quenched by deprotonation with cyclopropanation to afford the key neutral

• , which is quenched by deprotonation to yield spiroluchuene A (20). An illustrative example of a complex cyclisation cascade with multiple ring-size modifications was documented by Dickschat et al. during the biosynthesis of the saturated sesterterpene subrutilane (22, see Scheme 6), catalysed by the

• . Subsequent 2,9- and 3,7-cyclisations afford the key carbocation intermediate 22f, which is finally quenched by a deprotonation with concurrent cyclopropanation, effectively contracting a cyclopentane to a cyclobutane, to yield subrutilane (22). Based on quantum chemical studies by Tantillo and Hong the

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• deprotonation. Examining the absorbance at 755 nm versus pH yields a second pKa value at 13.0 ± 0.11 (Supporting Information File 1, Figure S26). As shown in Figure 1B, the corresponding disulfonate of 6,6’-dibromoindigo, 9, shows similar UV–vis spectra to compound 10. Specifically, 9 shows a λmax at 606 nm and

• for this second deprotonation, but we estimate it to be above 12.5. Finally, analogously with 5,5’-indigodisulfonic acid (indigo carmine), both 9 and 10 can be readily reduced to their leuco forms using sodium dithionite, yielding a clear solution (Supporting Information File 1, Figures S19 and S27

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• by BH+ from the side opposite to the –CH(EWG)2. Thus, only diastereomer III is formed. Deprotonation of this intermediate leads to carbanion IV. For further attack by the carbanion center to the carbon atom bonded to bromine, the –C(EWG)2 moiety must hold an anti-periplanar position relative to the

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• esters [25], we initially envisioned the formation of dianion I from maltol (2), which should undergo selective C-methylation with methyl iodide to furnish ethylmaltol (1) (Table 1). Typical deprotonation conditions employed for β-keto esters, i.e., sequential treatment of maltol (2) with equimolar

• opted for deprotonation with lithium reagents. Attempted double deprotonation with methyl lithium afforded a complex reaction mixture, from which ethylmaltol (1) was isolated in 11% together with an inseparable impurity tentatively assigned as 6 based on NMR analysis (Table 1, entry 2). Switching to the

• hydrolysis of 9e furnished ethylmaltol (1) in 95% yield. Screening of different bases for the methylation step of 8e revealed LiHMDS to be superior to NaHMDS. Various tert-butoxide bases as well as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were ineffective for deprotonation (see Supporting Information File 1

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• acid, presumably through an epoxide opening, 1,2-hydride shift, and deprotonation, alcohol 69 was obtained. These two transformations were combined to achieve rearrangement of 57 to 69 in 71% in one single step. The exo-methylene group was selectively hydrogenated, the C17-alcohol eliminated, and then

• C12,15-glycol 102. The glycol was subjected to periodate cleavage, which was followed by intramolecular aldol reaction to effect contraction of the C-ring. The observed regioselectivity was rationalized by steric influence of the C19-methyl group hindering deprotonation at C11. Thus, desired cyclization

• corresponding to deprotonation at C14 was observed. The elimination to the enal did not occur spontaneously but required heating of the corresponding C12-mesylate, hinting at the ring strain accompanied by formation of the double bond in the trans-hydrindane system. The enal was subjected to a Wittig

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• band around 350 nm was observed. This increase can be explained by deprotonation of the structures, which facilitates solvation effects by water molecules. The cause for the tautomerism effect at acidic pH may be due to the protonation of the basic site of the amino group present in the derivatives

• the electronic density towards the acceptor regions (Figure 10), which inhibits the intramolecular charge transfer upon excitation. It is important to note that protonation and deprotonation can significantly alter the HOMO–LUMO gap of a molecule by disrupting its electronic structure. In general

• , protonation of these compounds resulted in a lowering of the HOMO energy level, leading to an increase in the HOMO–LUMO gap and, consequently, greater molecular stability. In contrast, deprotonation led to an increase in the LUMO energy level, with little influence on the HOMO energy. Notably, the neutral

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• , deprotonation, and intramolecular addition to ketone. Treatment of the silacycle with MeMgCl cleaved the Si–O bond and subsequent intramolecular nucleophilic substitution of the chloride with the adjacent hydroxy group yielded TMS-epoxide 41. Protonic acid-mediated opening of the TMS-epoxide, accompanied by TES

• deketalization afforded carbonate 58. A palladium-catalyzed decarboxylative alkenylation reaction was then carried out across the less hindered face of the six-membered ring to connect C5 and C6. Selective deprotonation and triflation at the C4 carbonyl group provided enol triflate 59. An intramolecular

• epoxide ring-opening afforded 71. To install the all-carbon quaternary center at C5, compound 71 was treated with t-BuOK and MeI, enabling the deprotonation of the α,β-unsaturated aldehyde and methylation at C5; this step also facilitated protection of the secondary alcohol. The aldehyde was reduced in

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• .1 initially engages substrate 7 through hydrogen bonding, forming intermediate Int 7. Subsequently, deprotonation of the naphthol group by quinuclidine yields intermediate Int 8. This intermediate then undergoes nucleophilic attack on the selenium atom in substrate 8, leading to the formation of the

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• not proceed to form the all-carbon quaternary center and only decomposition of 21 was observed. The failure is likely due to the sterically hindered environment of the substituted β-lactone ring which precludes the C–H insertion or deprotonation of the β-lactone and interrupted the generation of the

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• base results in the deprotonation of the ammonium site and shuttling of the macrocycle to the urea site. Whereas, upon addition of acid, the macrocycle returns to the protonated BAA site. Notably, the rotaxane exhibited high fluorescence intensity due to aggregation in acetonitrile with high water

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• cyclization and subsequent deprotonation furnished 1,3-disubstituted or 1,2,3-trisubstituted naphthalenes 29 (Scheme 7, path a). When the alkyne terminus was iodo-substituted or unsubstituted, the 5-exo-dig cyclization pathway proceeded via selective activation of the iodoalkyne, generating 1-methyleneindene

• ]. Ph3PAuCl/AgOTf catalyzed a tandem 7-exo-dig cyclization followed by a cyclobutyl ring expansion process, yielding intermediate 84. The deprotonation followed by protonolysis-mediated gold elimination delivered the ring-expanded product 85 (Scheme 18, path a). When a bulkier ligand was used, steric

• featuring an isopropyl substituent was transformed to a carbene intermediate 121 via a gold-catalyzed 5-endo-dig cyclization. When the Ph3PAuCl/AgOTs system was used, indene derivative 122 was obtained by deprotonation (Scheme 25, path a). In contrast, 1,2-hydrogen migration was favored using the Ph3PAuCl

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• ] generated [Cp2Fe]+ along with cathodic reduction of MeOH to H2 and MeO− acting as a base. Deprotonation of 1a using MeO− produced the anion A, which underwent single-electron transfer (SET) with [Cp2Fe]+ to give the nitrogen-centered radical B with regeneration of [Cp2Fe] [164][165][166][167][168][169][170

• formed H2 and HO−. The anti-nucleophilic attack of the N atom in A and the following HO− facilitated deprotonation and formed the corresponding 3-iodoindole 11a. Excessive-reduction (a minor side-reaction) of 11a took place as well in certain instances, resulting in the formation of 12a. And for the

• generation of 12a in Cu rod electrodes, the Cu anode was expected to liberate Cu+ into the reaction mixture. The reaction of this Cu+ with DMSO and I− afforded (DMSO)nCuI, which was coordinated with C≡C to give B. The intermediate C was obtained by cyclization of B and deprotonation. Further protonation of C