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

• combinations of macrocyclic cavities adorned with functional groups (Figure 3A) [97][98]. These grand “set-piece” enzyme models typically showed only modest catalytic enhancements for enzyme-relevant reactions like the hydrolysis of activated esters, and so mostly contributed to the view that enzymes do not

• 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

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

• it to obtain significant stereoselective glycosylation products in good yields. Acetyl and benzoyl protection: The total synthesis of oligosaccharides has seen numerous illustrations of the participating role of the acyl esters. Citing a few references in order to elaborate the mechanistic protocol

• in machine-assisted oligosaccharide synthesis. 4-Acetoxy-2,2-dimethylbutanoyl (ADMB) esters were reported by Ensley and co-workers [108] having similar properties with the pivalate group. The facile removal of the C-2-ADMB group with a catalytic quantity of diazabicycloundecane (DBU) in methanol at

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

• IR spectra of compounds 5a–6d containing an alkoxyfuropyran fragment shows that in the case of methyl esters 5a, 6a, and 6c the absorption band of the alkoxycarbonyl function is shifted to a lower frequency region (1714–1721 cm−1), while ethyl esters 5b, 6b, and 6d are characterized by higher

• 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

• ethyl esters 5b and 6b is −15.6(2) and −11.5(2)°, respectively, indicating that in the case of methyl esters, the alkoxycarbonyl fragment is less out of plane, causing a greater conjugation with the furan fragment. The possibility of exhibiting fluorescent properties was investigated for tetracyclic

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

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

• esters containing a quaternary stereocenter, and the control of regioselectivity depended on the bulkiness of the substrates. Additionally, the electrochemical system served as an internal syringe pump, generating quinone from hydroquinone in situ through anodic oxidation, which enhanced the

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

• ] cycloaddition reaction with the nitroalkene produces the pyrrolidine XXVII, which then aromatizes by extrusion of HNO2 (Scheme 21) [38]. Substituted pyrrolidines 30 were achieved in an enantioselective form starting from amino acid esters, electron-poor olefins and 4-substituted-2-picolinaldehydes or 4

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

• positions 6 and 7, but the best results were consistently achieved by exchanging the hydrogen in position 8. Such products along with the ones containing various butyl, methyl, and ethyl esters on the indolizine ring were obtained in moderate to good yields with repeatedly high enantiomeric purity of 97

• a gram scale gave the product with analogous yield and enantioselectivity (73%, 96% ee). Hydrogen-bond-stabilized axially chiral N-arylquinones 133 were prepared by reaction of quinone esters 131 with anilines 132 mediated by CPA (R)-C23 (Scheme 39) [67]. Apart from respectable yields and remarkable

• ]. N-Naphthylglycine esters 198 reacted with nitrosobenzenes 199 and the authors reported moderate to good yields with remarkable enantioselectivities. Configurational stability of a representative product 200 was observed in toluene at 120 °C for 24 h with no deterioration of the ee. The practicality

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

• %). This cascade involves an initial Suzuki–Miyaura cross-coupling reaction between 1,8-dihalonaphthalenes and heteroarylboronic acids or esters, followed by an intramolecular C–H arylation under the same conditions to yield the final heterocyclic fluoranthene analogues. The method was further employed to

• -catalyzed annulation reaction between bromo-chloronaphthalene dicarboximides 6 and heteroarylboronic esters that enabled the syntheses of acenaphthylene-fused thiophene and indole derivatives 7 having donor-acceptor units (Scheme 1a) [40]. In 2021, Jin and co-workers developed an elegant Pd-catalyzed

• 1,8-diiodonaphthalene (12) and a broad range of arylboronic acids and esters to afford substituted fluoranthenes 13 in good to high yields (Scheme 1d) [43]. In that work, we had only one example of a heterocyclic fluoranthene analogue where the use of 4-pyridylboronic acid provided the corresponding

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

• reactivity with in situ-generated sulfenate anions, from β-sulfinyl esters, to achieve S–N bond formation. The importance of establishing this S–N bond results from the widespread presence of sulfonyl-containing bioactive compounds, such as the sulfonamide group which can be found in many pharmaceuticals

• lengths and angles fall within the expected range for similar compounds [31]. Later, the β-sulfinyl esters 4 were prepared by Michael addition reaction of thiols and α,β-unsaturated esters [32], followed by oxidation of the corresponding sulfides 3 using two different oxidizing agents (oxone and m-CPBA

• these conditions, no amine-transfer products 5aa (sulfonamide) or 6aa (sulfinamide) were observed. Next, and with the optimized conditions in hand (Table 1, entry 7), we studied the scope of the reaction by varying both the β-sulfinyl esters 4 and the electrophilic amines 2. Thus, a variety of

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

• functional groups for subsequent product diversification (Scheme 1). For example, protected alkynylboron reagents can be employed [35][36][37], such as N-methyliminodiacetic acid (MIDA)boronate esters [38], potassium trifluoroborates [39], and others [40][41][42]. Similarly, organosilicon reagents have

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

• their amides, esters, and azides by FeCl2-catalyzed isomerization of 3-aryl-5-chloroisoxazole-4-carbonyl chlorides into 3-aryl-2H-azirine-2,2-dicarbonyl dichlorides followed by their reaction with nucleophiles are reported. Two approaches to the preparation of 3-aryl-5-chloroisoxazole-4-carbonyl

• -ylcarbonyl)-2H-azirines, 1-(2H-azirine-2-carbonyl)benzotriazoles, 2H-azirine-2-carbonyl azides, anhydrides, amides, esters, and thioesters of azirine carboxylic acids, as well as azirine carboxylic acids themselves, have been prepared over the last decade (see [2] and references therein). Azirine-2

• reaction sequences for the synthesis of 3-aryl-5-chloroisoxazole-4-carbonyl chlorides have been developed. These compounds are convenient precursors for the preparation of 2H-azirine-2,2-dicarboxylic acids and their derivatives such as amides, esters and azides, via an Fe(II)-catalyzed room temperature

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

• % yield, however, the related benzyl derived ylides gave 3i and 3j in 73% and 61% yields, respectively. Phenyl esters performed well with this methodology (3k,l), but switching to anilide-derived ylides were consistently poorer performing. The N-phenyl ylide derivative reacted to produce 3m in only 50

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

• , Tomilov et al. described the formation of tetrahydropyridazine 3,4,5,6-tetracarboxylic esters in 42% yield upon the decomposition in chloroform at 60 °C of methyl diazoacetate in the presence of pyridine and catalyzed by rhodium(II) acetate (Scheme 1b) [24][25]. More recently, an unusual [4 + 2

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• intramolecular SNAr reactions. Ugi-4CR/deprotection/cyclization (UDC) strategy: In the UDC approach a protected amine and an electrophilic functional group like esters or ketones are used. Convertible isocyanides can also be employed. Once the Ugi reaction is completed, the protecting group is removed, and the

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• alkynylation reaction of N-hydroxyphthalimide esters (NHPI) 92 with alkynyl p-tolylsulfones 93 in the presence of H2TPP (18) resulted in 44–93% yields depending on the substituents (Figure 17b and c). Furthermore, the authors approved the biological application of porphyrin photoredox catalysts by using them

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

• compounds (β-diketones, β-ketoesters, and malonic esters) with TBHP via homogeneous and heterogeneous Cu(II)-catalysis were developed (Scheme 10) [45][46][47]. It was assumed that the reaction pathway includes the formation of diketonate complex A from β-dicarbonyl compound 19 and copper(II) salt, which

• photocatalytic system under visible light irradiation (443 nm) [56]. Peroxidation of β-ketoesters, cyanoacetic esters, and malonic esters 37 was performed using the TBAI/TBHP system (Scheme 15) [57]. The highest product yields in the TBAI-catalyzed peroxidation were achieved with malonic acid esters, in contrast

• . There is no consensus on the nature of the iodine species formed in reactions when using iodine-containing agents and their role in the mechanism of peroxidation. The selective peroxidation of malonodinitriles and cyanoacetic esters 39 with TBHP under Cu-catalysis without oxidative destruction was

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

• Mike Brockmann Jonas Lobbel Lara Unterriker Rainer Herges Otto Diels-Institute of Organic Chemistry, Christian-Albrechts-Universität zu Kiel, Otto-Hahn-Platz 4, 24118 Kiel, Germany 10.3762/bjoc.20.248 Abstract In this study, novel fluorinated carboxylic acid esters of the generic structure TfO

• converted into the methyl esters 10 (54%), 11 (52%), and 12 (46%). The benzyl-protecting group was removed hydrogenolytically to give products 13 (85%), 14 (65%), and 15 (99%). The alcohols were then converted to the triflates 16 (28%), 17 (41%), and 18 (63%). We have chosen 3,4,5-trimethoxybenzaldehyde (19

• favor an alternating sequence of the chains pointing upward and downward. Conclusion This study reports the synthesis of perfluoroalkyl carboxylic esters with CH2–OTf groups in the ω-position of the type TfO–CH2–(CF2)n–COOCH3 (n = 2, 4, 6, Tf = triflate). The latter compounds were used in Williamson

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• decarboxylation of α,α-difluoro-β-keto acid esters 11 with the help of aryl(TMP)iodonium tosylates 12 in toluene at 100 °C to yield α,α-difluoroketones 13 in excellent yield (Scheme 4). The reaction proceeds via ligand exchange between the fluorinated carboxylate and the tosylate anion of the hypervalent iodine

• underscored by the successful conversion of various α,α-difluoromethyl ketone groups into corresponding esters, amides, and difluoromethyl groups [58]. In 2021, Nilova and colleagues outlined an approach for the synthesis of highly hindered 1,2,3,4-tetrasubstituted benzenoid rings 15 using arynes generated

• various substituents on the aromatic ring. Additionally, a variety of substituted esters, ketones, and nitriles were found to be compatible with the reaction. Additionally, the same approach was used for the aryl sulfonylation. Trisubstituted allylic sulfones 35 were synthesized by reacting MBH acetate 33

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• ] because of their easily modifiable dipeptide frameworks. Several methods exist for accessing PCPAs, such as the amination of 1-halo-1-alkynes [16][17], tandem reactions of α-imino esters with nucleophiles and electrophiles [18], and the nucleophilic addition of an acetylide to α-carbonylated N-acylimines

• esters and N-acyl groups is limited to acetyl, benzoyl, and alkoxycarbonyl groups [15]. Conversely, NAIs derived from α-oxomalonic acid diester are more versatile. Nagao et al. prepared NAI 2 through the aza-Wittig reaction of diethyl mesoxalate (DEMO, diethyl α-oxomalonate). However, only the N-acetyl

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• literature procedure [35]. With initial success in the synthesis porphyrin 26, this Suzuki coupling reaction was performed on 13, for a range of boronic acids/esters as shown in Figure 2 and Scheme 2. Boronic acids/esters were chosen based on their electronic properties (activating/deactivating) as well as

• stability than boronic acids and other employed esters as the four methyl groups protect the boron center from attack of water [44][45], preventing protodeboronation from the hydrolysis route. However, protodeboronation can be complex when it comes to pKa considerations, for example, 3,5

• -analogue porphyrin 35. Use of the electron-donating p-tolylboronic acid (20), resulted in a 30% yield (Table 2, entry 12) again requiring an increase of catalyst loading and a change of base to K3PO4. Heterocyclic boronic acids/esters were again investigated for coupling reactivity with a consistent trend

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• , which further limits the preparation of the related compounds. He et al. [65] used tetramethyldiaminomethane as a suitable surrogate of dimethylamine to achieve the asymmetric dimethylamination of yne-allylic esters, providing an efficient and convenient pathway for the synthesis of enantioenriched 1,4

• transformed into a series of useful molecules, enabling them an important backbone in organic synthesis. Lin et al. [66] used sodium sulfinates as the nucleophiles to realize the asymmetric sulfonylation of yne-allylic esters. The reaction can be carried out under mild conditions with good to excellent regio

• confirmed that a copper–ligand monomer complex exists in the mechanism through nonlinear relationship experiments and kinetic studies (Scheme 17). He et al. [68] developed the regio- and enantioselective monofluoroalkylation of yne-allylic esters using fluorinated malonates as the starting materials, giving

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• -dimethylalk-5-enoates in a homologous series from C11–C16, were characterized by GC–MS and GC–IR analysis and various microderivatization reactions including hydrogenation and esterification leading to methyl and pyridylmethyl esters. In addition, dimethyloxazoline formation helped to localize the double bond

• various lipid classes including sterols, triacylglycerols, and common fatty acid methyl esters [15]. Mass spectrometric analysis of the lipid content of crotalines, mainly the Western Diamondback Rattlesnake (C. atrox), confirmed the presence of cholesterol [3][6][11][16], fatty acids [11], fatty amides

• ion at m/z 141 showed a composition of C8H13O2 (m/z 141.0898, calcd. 141.0910). Derivatization with N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) or trimethylsulfonium hydroxide (TMSH) converted A–F into the corresponding trimethylsilyl or methyl esters (Am–Fm) (Supporting Information File 1

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• > secondary. Functional groups such as silyloxy, amides, ethers, esters, enolizable ketones, and nitriles were found to be compatible with this transformation. Late-stage functionalization of different molecules was demonstrated; for example, the azidation of ibuprofen occurred preferentially at the secondary

• constant voltage (CV) conditions and light irradiation under a nitrogen atmosphere. This method demonstrates broad compatibility with various functional groups and complex substrates, including alcohol, carboxylic acid, esters, alkyl chloride, and tosylate groups. Notably, the LSF of compounds such as

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

• mainly afford 2-substituted 3-hydroxyesters usually in a highly anti selective manner. Keywords: α,β-unsaturated esters; epoxyesters; fluorine; Grignard-based cuprates; nucleophiles; Introduction Fluorine-containing compounds have been utilized in diverse fields due to their special character

• t-BuO2Li reagent [31], we speculated that NaClO·5H2O would similarly work for the corresponding Z-1 with retention of stereochemistry. The procedure found here was also applied to the three representative CF3-containing α,β-unsaturated esters,1h–j [42] with different substitution patterns (Scheme 2

• spectra for the compounds 11a and 11a-D. Expectation of the regio- as well as stereoselective reactions of 2. Attempts of the present epoxidation to other α,β-unsaturated esters, 1h–j. Introduction of additional halogen atoms at the 2-position of the compound 2b. Clarification of the stereochemistry of

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• diarylacetic acids from diarylmethanol species and carbon dioxide without transformation of the hydroxy group into appropriate leaving groups, such as halides and esters including carbonates. Keywords: C(sp3)–O bond cleavage; diarylacetic acid; diarylmethanol; electrochemical reduction; fixation of carbon

• ][9][10][11], yielding phenylacetic acids. For example, Troupel et al. successfully performed electrochemical reduction of benzyl ethers and several esters such as acetate, trifluoroacetate, benzoate, and dibenzyl carbonate derived from benzyl alcohols, including 1-phenylethanol compounds, in the