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

• such as nitroalkenes and enones were completely regioselective, yielding regioisomers in which the activating group is located adjacent to the pyridyl moiety (86–96% ee). The work of Carretero's scientific group has developed effective methodologies for the enantioselective synthesis of complex

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• heterodimer with a C4v-symmetric tetratosylureacalix[4]arene 52 (each as a pair of enantiomers). Similarly, the C2v-symmetric tetraureacalixarenes of the second type should furnish C2-symmetric homo- or heterodimers as single regioisomers (each as a pair of enantiomers), whereas homo- and heterodimers formed

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• lower donor character compared to pyrrolidine, but higher than that of morpholine and piperidine. As a result, a mixture of products 2l and 2l′ is formed. Starting dihydrothiophenes 1 form more stable anions B in comparison with regioisomers 4 due to the delocalization of the negative charge over 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

• polynitrated side-products, but was unable to effectively separate the two regioisomers, and this mixture was carried on to the next step. The regioselectivity of nitration obtained in this reaction was better than the 5:4 ratio of 3 to 7 reported for a traditional nitration of p-bromotoluene [5][19]. Despite

• bromine (Scheme 4C). Similar yields, 55% relative to starting 3, were obtained when the mixture of 3 and its regioisomer 7, obtained from the previous step, was brominated using the optimized reaction conditions. Compound 6 was purified and separated from any regioisomers by recrystallization from a

• mixture of hot toluene and hexanes. The efficacy of recrystallization was especially useful to our synthetic goal as it obviated the need to separate the mixture of regioisomers 3 and 7 from the nitration step, which were challenging to purify from each other. Product 6, which was isolated as an off-white

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• olefins or carbonyls are present, often requiring fine-tuning of the reaction conditions to prevent overreduction. Disruption of aromaticity also creates multiple potential reduction sites, and subtle electronic or substituent differences can lead to regioisomers, especially in polysubstituted or fused

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

• rearrangement was carried out with trifluoromethanesulfonic anhydride leading to a mixture of regioisomers 23 and 27, with 23 being convertible to 27 by addition of DBU. The A–E-rings have, thus, been installed with correct stereoconfiguration, therefore the last steps of the sequence focused on the

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• -shifting of UV–visible absorbance signals relative to their non-annulated counterparts. Structural rigidity of annulated systems compared to non-annulated counterparts was reflected by emission signals with increased intensity and decreased Stokes shifts. Five benzotriazolophenanthroline regioisomers

• other bioactive properties [37][38][39][40][41][42][43][44]. In contrast, examples of 1,5-diaryl-1,2,3-triazoles with quinoline or isoquinoline subunits are lacking [45]. The neighboring proximity of the arene subunits in such 1,5-regioisomers allows for potential intramolecular annulation to form

• prepared using non-brominated azide and alkyne reactants (Figure 4). Although 1,4-disubstituted-1,2,3-triazoles possessing quinoline and isoquinoline subunits are known [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44], no prior examples of analogous 1,5-regioisomers have

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• less hindered site. Halogenated substrates 1q and 1r (3-Cl and 3-Br substitution) delivered products 2q (37%) and 2r (31%) in moderate yield. Notably, the reaction of 1r also furnished 2a (9%), indicating competitive debromination. Finally, benzocarbazole substrate 1s afforded a mixture of regioisomers

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• of LG and 1,3-butadiene (Scheme 3). The ratio of the resulting regioisomers was 5:3 in favor of the 5-methoxycarbonyl derivative 17a. The synthesized cyclopentane derivatives 17a,b, 18, and 19 may be useful for the preparation of iridoids and other biologically active cyclopentanoids. An alternative

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• a thermal Diels–Alder cycloaddition, which afforded a mixture of stereo- (endo/exo) and regioisomers, among which the desired product 46 was obtained in 45% yield as a racemic mixture. After triflation of the free hydroxy group of 46 to provide 47, an intramolecular Heck reaction was employed to

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• difference between TS30b (ΔΔG‡ = 0.3 kcal/mol) and TS30a (ΔΔG‡ = 0), resulting in the formation of 31 as a 1:1 mixture of regioisomers (Scheme 5c). In this work, to address unsatisfactory C4 stereochemistry in initial synthesis, the authors introduced a double bond to alter substrate conformation, enabling

• separable regioisomers: gracilisoid F (54) in 42% yield and gracilisoid H (56) in 40% yield, respectively (Scheme 8). Here, light triggered a regiodivergent Norrish–Yang cyclization, while the acidic nature of silica gel sufficiently promoted an α-hydroxy ketone rearrangement. This type of rearrangement was

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• analysis. The major one 48b was used for further study to install the pyrrolidine system. Thus, nucleophilic addition of an N,O-enolate, derived from precursor 49 with LDA, to the ketone functionality in 48b was implemented to generate a pair of inseparable regioisomers 50a and 50b, arose from C4 and C7

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• unsymmetrical diisocyanide was used, the initial isocyanide insertion was found to be non-regioselective, delivering a 1:1 mixture of regioisomers (17c and 17c’). Intriguingly, 17a could act as a chiral acylating reagent, applying in the kinetic resolution of racemic primary amines rac-18. Additionally, after

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• one out of these three molecules investigated as the other “incorrect” predictions are due to a problem with the underlying dataset. Since we do not assume that the energies obtained at the r2SCAN-3c(CPCM)//GFN1-xTB(ALPB) level are accurate enough to separate regioisomers which are close in energy, we

• . Five reaction sites were predicted to be within 1 kcal·mol−1 of another possible reaction site in the reactant and were therefore classified as semi-correct, meaning we cannot predict with our model which of the two regioisomers will be the main product of the reaction. Refinement using r2SCAN-3c

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• ][3][4] and regiodivergence [5][6]. In both cases, starting from the same substrate, different stereoisomers (diastereomers and enantiomers) or regioisomers can be obtained under different reaction conditions. Over the past two decades, researchers have found that by changing reaction conditions and

• modifying the substrate, two structurally distinct products that are neither stereoisomers nor regioisomers can be obtained from the same starting material (using the same reagents, if necessary), and significant progress has been made in recent years. Controllable/divergent synthetic strategies have

• control regioselectivity. It profoundly influences reaction kinetics, stability of intermediates, and reaction equilibria. Through precise temperature modulation, chemists can effectively steer the formation of regioisomers, often achieving desired selectivity with minimal alterations to other reaction

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• derivatives are isolated as side-products. Interestingly, when Liu et al. [40] modified this reaction by using a copper(II) catalyst under aerobic oxidative conditions, the regioisomers III (2-arylquinolines) were obtained (Scheme 9). To rationalize this singular result, the authors proposed a mechanism in

• cases, phenylalanine and aspartate derivatives react with aniline compounds to provide quinoline regioisomers IV and V, respectively [41]. These reactions are suited for a broad range of reactants with both electron-donating and electron-withdrawing groups. DMSO activation through a Pummerer reaction

• ][89][90][91]. It is also known that two regioisomers can be generated during the GBB reaction depending on the nature of the amidine and the aldehyde used and, therefore, the type of imine formed [85][90]. As formaldehyde is a very reactive molecule, it will be more susceptible to form imines with

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• family of photochromic compounds. This study explores the photochromic properties and thermal back reactivities of various aza-diarylethene regioisomers (N1–N4 and I1–I4) in n-hexane. These molecules exhibit fast thermally reversible photochromic reactions driven by 6π aza-electrocyclization. Kinetic

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• nonfluorinated Rf groups which sometimes suffered from the contamination of the regioisomers as a consequence of the regiorandom attack of nucleophiles [22][23][24][25][26]. Despite such significant advantage, compound 2a was previously prepared only by 1) the LDA-mediated iodination-intramolecular ring closure

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• is that the reaction with methylhydrazine leads to two different regioisomers. Shen et al. used a concept developed by them for the C-acylation of β-ketoesters for the one-pot synthesis of pyrazoles. SmCl3-catalyzed acylation of these yields the 1,3-diketones 4, and after cyclization with hydrazine

• three different regioisomers when employing different isothiocyanates 19. However, easy separation by LC–MS could be achieved, as demonstrated for one-pot process generated pyrazoles 21a–f. The reaction demonstrates high tolerance to steric hindrance and electronic factors, enabling the synthesis of

• employed, likely due to the more electron-rich internal nitrogen atom reacting with the Michael system. When phenylhydrazine is used, an inverse reactivity is observed [73][74][75]. Remarkably, when hydroxyethylhydrazine is utilized, a mixture of regioisomers is formed, likely attributed to steric

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• the impact of gauche and anomeric effects on the conformer stabilities of different stereo- and regioisomers. Initially, we conducted a benchmark assessment comparing the optimal density functional theory method with coupled cluster with single and double excitations (CCSD) calculations and

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• , ester, and phthalimide proceeded smoothly with good yields and excellent regioselectivities to access the oxazoline products as single regioisomers (Figure 3, products 18–22). The o-bromo-substituted styrene also afforded the corresponding product 23. Furthermore, 1,1-di-substituted α-methylstyrene and

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• the pyrazole tautomerism [28], the formation of two possible regioisomers, 17 and 18, was anticipated and could be confirmed experimentally. Depending on the employed halide 16, the distribution of the obtained products varied. A considerable excess of the dominating isomer with yields of up to 70

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• for the synthesis of dialkyl bromoketones would result in a mixture of regioisomers given the presence of enolizable protons on each side of the ketone (Scheme 1b). Recently Toy et al. have disclosed the selective synthesis of unsymmetrical α-haloketones by reductive halogenation of an α,β-unsaturated

• . TsOH·H2O (0.2 equiv) in acetonitrile. These reaction conditions afforded the desired product 2a in moderate yield (51%), along with 21% mixture of regioisomers 3a and 3a’ obtained from Ritter-type reaction of 1a with CH3CN in the presence of HTIB (Table 1, entry 1). We explored the influence of different

• α-bromoketones (2e,f) with unaffected reactivity or yields. Notably, 15–20% Ritter-type side products were obtained with all these substrates as a mixture of regioisomers. Surprisingly, even substrate 2g did not provide a higher yield of the desired α-bromoketone product, despite the absence of

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• with excellent properties as organic photovoltaic materials [9][10][11][12][13][14]. Furthermore, regioisomerically pure bis-functionalized fullerenes function better as electron acceptors in organic thin-film solar cells than mixtures of the corresponding regioisomers do [12][13][14]. Therefore

• between a pentagon and a hexagon). If the second additions proceed also at the 6,6-bonds, then nine regioisomers are possible for bis-additions, as shown in Figure 1 [4][5]. In addition, when the second addends are identical to the first, the e' and e'' isomers are the same adducts, thereby affording

• eight possible regioisomers for bis-addition reactions. Hirsch and co-workers reported two-fold additions of C60 using the Bingel–Hirsch and the Bamford–Stevens reactions as well as nitrene addition reactions, indicating the formation of regioisomers as anticipated from the possible addition sites in