Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• of N-alkylation on the non-chlorinated unit B derivatives. Results and Discussion For the synthesis of unit B derivatives with amino groups instead of the naturally occurring methoxy group ᴅ-phenylalanine served as the fundamental substrate (Scheme 1). Nitration [23] followed by methyl ester

• macrolactamisation [21]. The syntheses of required unit A [28], C [29][30], and D [31] building blocks were accomplished as described previously. tert-Butyl-protected leucic acid 14 and Fmoc-β-aminopivalic acid (15) were connected by Steglich esterification (Scheme 2) and after cleavage of the tert-butyl ester group

• indicate the major presence of a fully deprotected and trifluoroacetylated seco-cryptophycin, most likely a TFA ester of one of the free hydroxy groups, a finding which might reason the comparably low yields (21–25%) of structurally similar unit B analogues reported earlier [21]. Contrary, diol 25 was

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• -amine reduction and tosylation from diethyl (S)-2-(hex-5-en-2-yl)malonate ((S)-6). The stereocenter in geminal ester (S)-6 could be derived from (R)-2-methyloxirane ((R)-2) via a ring-opening reaction and a stereospecific inversion of the chiral secondary tosylate (R)-5. Following the similar procedure

• oxidation. The optical purity of the chiral secondary alcohol (R)-4 was more than 99% ee, determined by 1H NMR spectrum of its Mosher ester [27][28]. The subsequent tosylation with p-tosyl chloride gave (R)-hex-5-en-2-yl 4-methylbenzenesulfonate ((R)-5) in 88% yield [29]. The reaction of (R)-5 with the

• enolate of diethyl malonate yielded (S)-2-(hex-5-en-2-yl)malonate ((S)-6), and realized a stereospecific inversion of chiral secondary tosylate (R)-5 [30][31]. The geminal ester (S)-6 was next treated with NaOH in methanol to afford (S)-2-(hex-5-en-2-yl)malonic acid ((S)-7) in 96% yield [32]. Then

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• , syn-(ethoxycarbonyl,methyl)bimane (Me2B) and syn-(methyl,methyl)bimane (Me4B), were also examined for this phenomenon but did not undergo the reaction. Results and Discussion Synthesis Bimanes are typically synthesized through a three-step process, as outlined in Figure 3. First, a β-keto ester 1

• in P-1 and the molecules pack in a different arrangement, where the double bonds are neither coplanar nor parallel. This product was obtained from propan-2-ol, which may have influenced the crystallization kinetics. The reactive packing mode of Cl2B is enhanced by the hydrogen bonding where the ester

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• with bis(pinacolato)diboron did not lead to the formation of the pinacolborane-substituted N-acetyl diazocine 18. Accordingly, the Suzuki–Miyaura reaction with inversed roles between N-acetyl diazocine boronic acid pinacol ester and aryl or alkyl halides could not be investigated. The Buchwald–Hartwig

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• traditional solution-phase synthesis. In fact, in the latter case, almost complete recovery of the starting material was observed. Second, the authors found that the replacement of diisopropylethylamine (DIPEA) with Hantzsch ester in the role of sacrificial reductant for the pinacol coupling of benzaldehyde

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• an electrochemical synthesis of cyclic diaryl λ3-bromanes under anodic oxidation conditions. Results and Discussion Symmetric 2,2'-dibromo-1,1'-biphenyl 4a possessing ethoxycarbonyl groups ortho to the bromine was chosen as a model compound for our study. We anticipated that the presence of the ester

• ester moieties is critical for the synthesis of Br(III) species: the removal of one ester group (4i–k), or its replacement by NO2 (4l) or SO2t-Bu (4m) substituents in 2,2'-dibromo-1,1'-biphenyls resulted in starting material degradation with no formation of the desired product (for a complete list of

• developed method represents a safe and inexpensive alternative to the commonly used thermal decomposition of potentially explosive diazonium salts. The successful electrochemical oxidation requires the presence of two chelating ester groups that stabilize the formed Br(III) species. Further work towards

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• work simply by bringing substrates arbitrarily close to a potentially reactive group [99][100]. One rare but important exception is Breslow’s use of two tethered cyclodextrins to locate hydrophobic ester substrates next to a metal ion. Breslow’s catalyst accelerates the hydrolysis of esters and

• phosphodiesters by 105–107 by electrophilic activation of ester and nucleophilic activation of water or peroxide at the metal ion [101][102]. The takeaway message is that polarization is most effective when it is bifunctional. In enzymes, there is never just a nucleophile – there is always a metal, “oxyanion hole

• typically not possible for imine [314] or metal-coordination cages [156][202][365]. Further, the robust amide cages could withstand harsh conditions such as ester hydrolysis, allowing access to the key acid-functionalized cages [38] that mimic aspartyl proteases and glycoside hydrolases. Otte has employed

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• groups interact with the anomeric carbon and thereby help in the formation of a specific stereocentre. So, modulating the neighbouring protecting group in the C-2 position of glycosyl donors helps in improving the stereoselectivity of the produced glycoside bonds. Ester-type participating protecting

• the cases (exception depicted for perbenzoylated SBox glycosides exhibiting superarmament [79] proving to be more reactive than the analogous perbenzylated donors) thereby reducing the reactivity of the glycosyl donors. The challenge is to activate the ester-protected glycosyl donor and to implement

• will do injustice to all the numerous other works with acetyl groups. An ester group similar to the acetyl building block, i.e., the benzoyl group, has also been extensively used for the same purpose. Although the use of a benzoyl group in comparison to the acetyl group deviates from the principle of

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• were evaluated for their antimicrobial, cytotoxic, and human carbonic anhydrase (hCA) inhibition potential. Results and Discussion Chemistry The targeted compounds were synthesized using the general scheme shown in Scheme 1. The ester group was introduced at the nitrogen of saccharine sodium (1) using

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• frequency values (1725–1731 cm−1). This observation may be due to the position of the ester fragment relative to the heterocyclic system. The analysis of the results of X-ray diffraction analysis shows that the torsion angle C(10)–C(3)–C(16)–O(17) of methyl esters 5a and 6c is −0.8(2), and 5(2)°, and of

• . In turn, in the IR spectra (KBr) of compounds 7a–f, absorption bands of the ester fragment in the region of 1714–1750 cm−1 and absorption bands of the carbonyl group of the amide fragment in the region of 1674–1688 cm−1 are observed, which suggests the existence of these compounds in the solid phase

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• the substrate, an activated ester 25, subsequently generating carbon-centered radicals without the need for sacrificial electron donors via a decarboxylation process. In reacting with electron-deficient alkenes or alkynes 26, these radicals further yield tetralin and dialin moieties 27, respectively

• hydrogen-atom-transfer mechanisms with a Hantzsch ester 34 as presented in Scheme 12. Moreover, the study has explored the impact of substrate steric hindrance and halogen bond strength on catalytic efficiency, revealing that bromo- and iodo-substrates react more efficiently, while chloro-substrates

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• conditions, we studied the possibility of generating active methylidene derivatives from malonic ester, Meldrum's acid, cyanoacetic acid ester, acetoacetic ester, acetylacetone and 1,3-diphenylpropane-1,3-dione (1). We found that, with the exception of malonic ester, all compounds reacted with formaldehyde

• acetylacetone from the inner vial into the outer vessel containing formaldehyde, which affected the yield of all [4 + 2]-cycloaddition adducts involving this CH acid, regardless of the choice of diene. For acetoacetic ester and 1,3-diphenylpropane-1,3-dione, it was found that in addition to the main products 5

• cyanoacetic ester and acetylacetone. The configuration of the products 4 and 5 was established by bromination of a small amount of these isomeric compounds in CDCl3 (Scheme 6) and subsequent analysis of the mixture by 1H NMR spectroscopy. For the stereoisomers 4, the main product was lactone 22, identified by

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• enantioselectivity. First, the reaction of ketimine ester 33 and 2,3-dimethylhydroquinone at 10 °C provided the chiral 1,4-addition product 35 via dynamic kinetic asymmetric transformation (DyKAT). Conversely, when the reaction was performed at −10 °C, the reaction pathway switched from DyKAT to kinetic resolution

• (KR) of the racemic ketimine ester, providing the same chiral product 35 with recovered enantioenriched starting material. Additionally, when a 1-naphthyl ester was used instead of a methyl ester at −10 °C, 1,4-addition followed by intramolecular tandem annulation generated the corresponding chiral

• product 36. Finally, using 1-naphthyl ester and relatively bulkier 2,6-dimethylhydroqunone as starting materials produced chiral 1,6-addition products 37. In mechanistic studies, using quinone 38 instead of hydroquinone 34 in the electrochemical-free process produced the desired product 36, with a similar

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• radical mechanisms. Synthesis of α-aminonitriles 1. Synthesis of β-amino ketone or β-amino ester derivatives 3. Synthesis of 1-(α-aminoalkyl)-2-naphthol derivatives 4. Synthesis of thioaminals 5. Synthesis of aryl- or amine-containing alkanes 6 and 7. Synthesis of 1-aryl-2-sulfonamidopropanes 8. Synthesis

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• -naphthols, new atroposelective reactions of quinones and iminoquinones were developed [63]. The reaction of quinones with an ester group 109 and indoles with alkyl substituents 110 catalyzed by CPA C29 provided products 112 with regioselectivity on the pyrrole ring of indole (Scheme 35). On the contrary

• arylpyrrole derivatives (R)-235 and 237 [101]. In the first case, arylpyrroles 235 reacted with either diethyl 2-oxomalonate or dihydroxymalonate ester derivatives 236 (Scheme 69). A kinetic resolution was done with arylpyrroles 235 and diethyl 2-oxomalonate. The possibility of the kinetic resolution was

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• -nitrostyrene (4a), precursor of most of the hallucinogenic 2C-X family (Table 1). This method was also tested on other types of scaffolds to investigate its potential general applications and effects on other substituents. As sodium borohydride per se does not reduce ester nor nitro functionalities [15][16][17

• ][18][19][20][21][22][28][29], the presence of the copper salt results in overcoming this issue and leads to isolated yields above 90% (7–9) (Scheme 2). Therefore, the NaBH4/CuCl2 system was proved to work on aromatic ester, nitro, and α,β-unsaturated nitroalkene functionalities. Our work demonstrates

• reductive methods used to date for the synthesis of substituted phenethylamines from their α,β-unsaturated nitroalkene analogues. Furthermore, the NaBH4/CuCl2 system is effective at reducing nitro and ester functionalities on aromatic structures, while leaving intact benzoic acid, amido- and halogenated

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• -diiodonaphthalene (12) and thiophene-3-ylboronic acid and ester derivatives 17 under the optimized conditions reported in our previous work (Table 1) [43]. Gratifyingly, the reaction worked smoothly with the use of thiophene-3-ylboronic acid (17a) to give acenaphtho[1,2-b]thiophene (15a) in 76% yield when Pd(dppf

• ] or catechol [47] boronic esters as the final products. Therefore, it is important that they can be directly utilized with our methodology without further boronic ester interconversions. To this end, we first tested the reaction of thiophene-3-ylboronic acid pinacol ester (17b), and we were pleased to

• see that the desired product 15a was isolated with a similar reaction yield (78%, Table 1, entry 2). Thiophene-3-ylboronic acid catechol ester (17c) was also found to be a competent reaction partner affording the final product 15a successfully, albeit in a slightly lower yield (69%, Table 1, entry 3

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• : 4a (2 equiv), NaH (2.4 equiv), 2a, TEMPO (10 mol %), degassed DMF (0.055 M). NO – not observed. Mechanism proposed for sulfonamide 5, β-sulfinyl ester 4, disulfide 7, and sulfide 3 formations. The ionic steps are illustrated in green, whereas the radical steps appear in purple [35]. Optimization of

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• yield of 4. Besides, the introduction of a boronic pinacol ester group, useful for subsequent post-functionalization, compound 7 was achieved in a relatively lower yield of 36%. Interestingly, the reaction also worked adequately for primary alkyl bromides with electron-withdrawing groups as demonstrated

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• chromene (12) were tolerated. Benzylic azides were accommodated including those bearing nitro (2), iodo (3), and boronic ester groups (5, 21). Strained rings were effective including cubane (18) and bicyclopentane (20). While 18 and 20 were isolated in lower yield, no evidence of ring opening was observed

• displaying an arylboronic acid and MIDA ester (22 and 23) gave no reaction, side reactions were observed with a dialkynyl germane (24), and the product derived from azide 25 was unstable to purification. To further demonstrate the compatibility and utility of germanyl alkynes in CuAAC reactions, we applied

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• a 4 mmol scale gave dimethyl ester 11a in 99% yield. Unexpectedly, the reaction of branched alcohols with diacyl chloride 2a failed. For example, the reaction with benzyl alcohol resulted in the formation of an overly complex mixture of products. Adding bases to trap HCl did not improve the

• situation. Dibenzyl ester 11c was prepared using traditional activation of carboxylic acid 6a, although the yield was only 23%. A higher yield of the branched ester 11d (86%, as a mixture of diastereomers) was obtained by carbene insertion, generated by blue LED irradiation of methyl 2-diazo-2-phenylacetate

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• reported the α-alkylation of carbonyl sulfoxonium ylides via a Michael addition approach that occurred without any competition from cyclopropanation [30]. While this reaction represented the first direct alkylation of sulfoxonium ylides, it was nonetheless limited to the more reactive ester ylide variants

• studies using methyl ester sulfoxonium ylide 1a and 2,2,2-trifuoroethyl(mesityl)iodonium triflate salt (2a), as model substrates (see also Table S1 in Supporting Information File 1). Combining these at room temperature in acetonitrile produced 3a in 8% 1H NMR yield (Table 1, entry 1). Repeating the

• scope and limitations of this novel transformation (Scheme 2). Initially, we investigated the effects of introducing various substituents around the ester group of the carbonyl sulfoxonium ylide. We discovered that the reaction worked very well for various alkyl ester derived substrates (3b–g). For

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• or ester substituent. Firstly, the group of Haupt reported the synthesis of ethyl esters of tetrahydromethylpyridazine in 20% yield in a mixture of methanol and water by the reaction of methylhydrazine with acetylene dicarboxylic esters through the formation of enhydrazine (Scheme 1a), [23]. Later

• the ester function, as previously reported [32][33][34][35]. The corresponding adducts 5a–f were isolated with good yields from 66 to 88%. In the case of hydrazides 5e and 5f, the mixture of diastereomers (1:1 ratio) could not be separated at this stage. Although no stereoselectivity is observed, it

• chromatography. With dipeptides 7e and 7f stereoisomerically pure, we next focused our attention on the preparation of novel peptidic structures to perform some conformational analyses. Starting from the methyl ester 7, each diastereomer was engaged in a classical sequence of saponification in the presence of

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• leads to the formation of the target product 139. Later, iron-catalyzed three-component reactions of α,β-unsaturated carbonyl compounds 140, aldehydes 141, and TBHP leading to α-ester-β-keto peroxides 142 have been developed (Scheme 45b) [106][107][108]. Radical coupling of arylaldehydes 144 with α,β

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• –CH2–(CF2)n–COOCH3 (n = 2,4,6, Tf = triflate) were synthesized. The triflates were reacted with 2-hydroxy-3,4,5-trimethoxybenzaldehyde via Williamson ether syntheses. The resulting electron-rich compounds were used as aldehydes in the Rothemund reaction with pyrrole to form ester-substituted porphyrins

• Williamson ether synthesis to yield 22 (78%), 23 (44%), and 24 (44%). Compounds 22, 23, and 24 were used as aldehyde components in the Rothemund-type synthesis of metal-free porphyrins 26 (9%), 27 (18%), and 28 (21%) (see Scheme 3). Metalation was achieved with nickel acetylacetonate to obtain the ester

• ester-functionalized aldehydes 22, 23, and 24. Conditions: a) NIS, TFA, Na2CO3, MeCN, reflux, 18 h; b) Cu2O·H2O, 2-pyridinaldoxime, TBAB, CsOH, H2O, N2, rt, 18 h; c) Cs2CO3, DMAc, N2, rt, 3 h. Porphyrin synthesis. a) Rothemund porphyrin synthesis of metal-free porphyrins 26, 27, and 28; b) metalation of