Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• applications in organic reactions. Similarly, Kunishima and co-workers (2021) utilized (N,N’-dialkyl)triazinedione-4-(dimethylamino)pyridine (ATD-DMAP) for the amidation of cinnamic acid (7) to generate the corresponding amide 10 in excellent yield (Scheme 5B) [37]. Mechanistically, the carboxyl group attacks

• group (2024) also investigated BH3·pyridine to catalyze amidation reactions with lower catalyst loading (Scheme 40B) [77]. Whiting and co-workers (2019) also used boranes to catalyze the direct amidation of carboxylic acids. In this work, they co-polymerized styrene, divinylbenzene and

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• in triarylmethyl radicals is by touching the triphenylmethyl scaffold itself, rather than only its substitution pattern. A variety of studies have been concerned with the pyridine-diphenylmethyl (PyBTM) motif, which has one of the para-carbons replaced by a nitrogen (see Figure 3) [56]. Surprisingly

• character of the fluorine substituent. When gold atoms are coordinated to the pyridine nitrogen, a ϕ as high as 8% has been observed [57]. The reason for this increase in ϕ to 8% for Au-Cl2PyBTM and 20% for Au-F2PyBTM is unknown, but the increase in the presence of a heavy atom might point at an improved

• the hole will reside on the mesityl and phenyl units (HDMO) and the electron resides on the PyBTM core (SOMO) (see Figure 4b). Instead of pyridine also carbazole (Cz) units have been coupled to produce N-carbazolyl-bis(2,4,6-trichlorophenyl)methyl radicals (CzBTM) (see Figure 5a). ϕ is highest at λem

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• Reaction exploration began with (E)-hex-3-en-1-yl methoxycarbamate, prepared in good yield from widely available trans-3-hexen-1-ol (Table 1) using a two-step protocol (1. 1,1’-carbonyldiimidazole (CDI), CH2Cl2; 2. MeONH2·HCl, pyridine) [33]. Based on insights from our work with I(III)-promoted alkene

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• achieved by using (R)-BTM (19), furnishing acetate 18 with satisfactory efficiency and enantioselectivity (37% yield, 85% ee). Finally, iodination of 18 employing Johnsen’s protocol (I2, pyridine) [39] provided α-iodoenone 13 in 89% yield. On the other hand, the synthesis of acetal aldehyde 14 commenced with

• 11 in the presence of AcOH by exposure to UV-light at 254 nm occurred exclusively to provide an inseparable mixture of 32 and 33 (Table 1, entry 5). Subsequent dehydration of the resultant mixture with SOCl2 and pyridine yielded separable enones 34 (51%) and 10 (9%) over two steps. The structure of

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

• structurally diverse macrocycles through the dynamic self-assembly of α,α’-linked oligopyrrolic dialdehydes and alkyldiamines (Scheme 10) [39]. Their investigation revealed distinct solvent-mediated selectivity in product formation. Condensation of the pyridine-bridged oligopyrrolic dialdehyde 37 with simple

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• coupling reaction of phenylpyridine with dialkylphosphonate in the presence of palladium. It should be noted that the presence of palladium is an essential factor, and the results showed that the coupling reaction failed in the absence of palladium. Under pyridine-mediated conditions, the reaction follows

• carried out in a divided cell using platinum electrodes as the anode and cathode in the presence of pyridine as a base and ligand (Scheme 14). The catalyst behavior of palladium is attributed to its ability to form palladium clusters of specific sizes that exhibit high catalytic activity. However, this

• corresponding phosphorylated propargyl alcohols (Scheme 19). The reaction yield showed that this method is not sensitive to electron-withdrawing or electron-donating groups at different positions on the aromatic ring. Most likely, the 3-substituted pyridine substrate and the enynes with nitro or carbonyl groups

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• previously [70]. Saponification of TetW1OAc with LiOH at 50 °C followed by acidification with 0.1 M HCl gives TetW1 in 69% yield [70]. Finally, the sulfation of TetW1 occurs upon treatment with py·SO3 (20 equiv) in dry pyridine to yield C1 as a white solid in 68% yield. In accord with the depicted C2v

• pyridine sulfur trioxide (1.1838 g, 7.437 mmol) was dissolved in dry pyridine (57 mL). The resulting mixture was heated at 90 °C under N2 for 18 h and then cooled to rt. The precipitate was collected by first decanting some of the solvent and then the remaining mixture was transferred to a 50 mL centrifuge

• , 10 min). The crude solid was analyzed by 1H NMR which showed residual pyridine. The crude solid was subsequently dissolved in water (150 mL) and re-precipitated by the addition of EtOH (144 mL) followed by centrifugation (7200 rpm, 5 min) to obtain a white solid. The solid was dried overnight under

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• (0.48 g, 3.9 mmol, 0.1 equiv) were added and the mixture was cooled to 0 °C before pyridine (9.41 mL, 117.0 mmol, 3.0 equiv) was added. After 1 h of stirring, the reaction was warmed to room temperature and further stirred for 16 h. Subsequently, the mixture was diluted with H2O (25 mL) and extracted

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

• , HOAt, N,N-dimethylformamide 0 °C for 2 h and at rt for 20 min, 11%; f) Grubbs II catalyst, CH2Cl2, reflux, 3 h, 84%; g) TFA, H2O, CH2Cl2, 0 °C to rt, 5 h, 91%. EDC·HCl = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; DMAP = 4-(dimethylamino)pyridine; TFA = trifluoroacetic acid; HOAt = 1

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

• observed. The synthesis of N-acetyl diazocines connected to heteroaromatic aromatic systems 14–16 was less successful. The pyridine-substituted N-acetyl diazocine 14 was formed in yields of 7% or 19% while furan- 15 and thiophene-substituted N-acetyl diazocine 16 could not be obtained. The reaction with

• (9) in ortho- and para-positions. The increase is even stronger if electron-withdrawing pyridine- (14), cyano- (23) or the strong +M amino substituents (21) are attached to the N-acetyl diazocine in meta-position. In contrast to the extended half-life of the unsubstituted amine 21 the Boc-protected

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

• -assisted departure of the leaving group, the lone pair of electrons of the nitrogen atom of the pyridine fragment of the Pic group participates to form a stable oxocarbenium intermediate 91 through the formation of a six-membered ring. The glycosylation mechanism proceeds via an SN2-like pathway through

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

• photocatalyst has shown superior yields compared to free-base and other phthalocyanin first-row transition-metal complexes, such as nickel. The choice of solvent was also critical for optimizing the reaction efficiency: a mixture of pyridine and methanol not only improved the yield but also has helped to

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

• , reacts with an enol species activated by the copper catalyst, affording the final product. The same research group reported an extension of this study by starting from arylacetylenes instead of arylketones [42]. Imidazo[1,2-a]pyridine derivatives 33 can be achieved by Cu(OTf)2-catalyzed multicomponent

• reactions starting from different reagents. In a first approach proposed by Meshram and co-workers, pyridin-2-one, O-tosylhydroxylamine and acetophenone treated in an ionic liquid assembled through the cascade formation of three C–N bonds to give the imidazo[1,2-a]pyridine scaffold 33 (Scheme 25) [43]. The

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• with feedback DOE facilitated the rapid identification of appropriate solvents. Notably, the use of DMSO, DMF, and pyridine led to an enhanced yield of the monoalkylated product. An experimental setup was developed for single-droplet studies of visible-light photoredox catalysis using an oscillatory

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

• , Ankara 06800, Türkiye 10.3762/bjoc.20.273 Abstract Acenaphthylene-fused heteroarenes with a variety of five- and six-membered heterocycles such as thiophene, furan, benzofuran, pyrazole, pyridine and pyrimidine were synthesized via an efficient Pd-catalyzed reaction cascade in good to high yields (45–90

• the regioselectivity of the reaction when 3-pyridylboronic acid is used as substrate as there are two different positions (C2 and C4) on the pyridine ring available for the C–H arylation step. Interestingly, azafluoranthene 15h was obtained as the only product in this reaction, albeit in a lower yield

• analogues via a Pd-catalyzed reaction cascade that consists of a Suzuki–Miyaura cross-coupling reaction followed by an intramolecular C–H arylation. These heterocyclic fluoranthene analogues include a variety of acenaphthylene-fused heteroarenes such as thiophene, furan, benzofuran, pyrazole, pyridine and

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

• functionalized thiols (aromatic, aliphatic, and heterocyclic) were chosen to produce the β-sulfinyl esters 4 (Scheme 3). We next investigated the electrophilic amination reaction (Scheme 4). First, different functionalized β-sulfinyl esters were reacted with BBX 2a. For the aromatic and pyridine moieties, the

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• Abstract The C–H arylation of 2-quinolinecarboxyamide bearing a C–Br bond at the N-aryl moiety is carried out with a palladium catalyst. The reaction proceeds at the C–H bond on the pyridine ring adjacent to the amide group in the presence of 10 mol % Pd(OAc)2 at 110 °C to afford the cyclized product in 42

• % yield, respectively. The related reaction is also carried out with amides of non-pyridine derivatives terephthal- and benzamides to afford multiply fused heterocyclic compounds in 81% and 89% yields, respectively. Keywords: intramolecular C–H arylation; multiply fused heterocycles; palladium acetate

• ; phosphine ligand; pyridine amides; Introduction Transition-metal-catalyzed synthetic reactions have recently attracted much attention in synthetic organic chemistry [1][2]. C–H Arylation reactions catalyzed by a transition metal are of particular interest because these reactions involve rather superior

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• /CH2Cl2 at room temperature (17% yield). Subjecting the methoxylated benzaldehyde intermediate 9 to a Doebner–Knoevenagel condensation with malonic acid and pyridine afforded the brominated cinnamic acid analogue 10 in 54% yield [19]. Amidation chemistry using carbonyldiimidazole (CDI) [18] and the

• (4-OCH3); LRESIMS (m/z): 293/295/297 [M + H]+. Doebner–Knoevenagel condensation of 3,5-dibromo-4-methoxybenzaldehyde with malonic acid 3,5-Dibromo-4-methoxybenzaldehyde (9, 80.0 mg, 0.27 mmol), malonic acid (56.0 mg, 0.54 mmol) and dry pyridine (1 mL) were refluxed at 100 °C for 5 h. The reaction

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

• reactivity compared to other alkynes, which typically require much shorter reaction times. Extending the reaction time provided a higher conversion to the product 14. Yields were observed to be greater for aryl azides (e.g., 4 vs 6). Heterocycles such as pyridine (1), pyrimidine (10), phenothiazine (11), and

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

• , 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

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• instead proceeded with addition of dichloro(pyridine-2-carboxylato)gold(III) complex in combination with silver triflimide, AgNTf2. A range of β-fluoroazepanes 7 were successfully synthesised with high enantiomeric purity in good yields. A mechanism for the synthesis of β-fluorinated piperidines was

• nucleophiles In 2000, Hara and co-workers reported the fluorocyclisation of unsaturated alcohols and carboxylic acids promoted by HVI reagents (Scheme 11) [36]. Using 4-tolyl difluoroiodane 10 as the reaction promoter, and pyridine·6HF as a source of fluoride, a range of unsaturated alcohols 23 to fluorinated

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• pyrindane – (E)-7-arylmethylene-2-chloro-6,7-dihydro-5H-cyclopenta[b]pyridine-3,4-dicarbonitriles – was developed. Tunable full-color emission was achieved for the synthesized push–pull molecules, solely by changing donor groups while keeping both the conjugated system and acceptor part of the molecule

• pyridine as an acceptor. The introduction of additional substituents to stilbazole makes it possible to change the optical properties of this molecular framework within a wide range [16][17][18][19]. This approach has found many applications in the synthesis of compounds that are used in various optical

• the facile preparation of molecular libraries with an emphasis on skeletal diversity for the development of new push–pull molecules. Results and Discussion Synthesis and structure determination A two-step procedure was used to obtain the target compounds (Scheme 1). Cyclopenta[b]pyridine derivative 2

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

• ether synthesis with 2-hydroxy-3,4,5-trimethoxybenzaldehyde (21). Conditions: a) K2CO3, benzyl bromide, abs. MeCN, N2, reflux, 18 h; b) TEMPO, KBr, NaOCl, NaHCO3, MeCN, rt, 76 h; c) MeOH, H2SO4, reflux, 18 h; d) Pd/C, H2, EtOH, rt, 24 h; e) Tf2O, pyridine, DCM, rt, 18 h. Synthesis of perfluoroalkyl

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

• Sondos A. J. Almahmoud,
• Joseph Cameron,
• Dylan Wilkinson,
• Michele Cariello,
• Claire Wilson,
• Alan A. Wiles,
• Peter J. Skabara and
• Graeme Cooke

Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244

• anhydrous chlorobenzene (6 mL). To the dark blue mixture titanium tetrachloride (100 μL, 0.840 mmol) and pyridine (130 μL, 1.68 mmol) were added and the mixture was stirred under reflux overnight. After cooling the reaction mixture to room temperature, it was poured into ice-water (50 mL) and extracted with

• in anhydrous chlorobenzene (6 mL). To the dark blue mixture, titanium tetrachloride (50.0 μL, 0.420 mmol) and pyridine (70.0 μL, 0.84 mmol) were added and the mixture was stirred under reflux overnight. After cooling the reaction mixture to room temperature, it was poured into ice-water (50 mL) and

• mL). To the dark blue mixture titanium tetrachloride (120 μL, 1.08 mmol) and pyridine (170 μL, 2.16 mmol) were added and the mixture was stirred under reflux overnight. After cooling the reaction mixture to room temperature, it was poured into ice-water (50 mL) and extracted with dichloromethane (3

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

• olefins, showcasing an efficient utilization of aryliodonium salts in the process. Later in the same year, Song and colleagues reported a protocol for the efficient synthesis of 2-aryl-substituted quinolines 27 and pyridine N-oxides 29 [63]. This reaction involved the selective arylation at the C2

• position of quinoline N-oxides and pyridine N-oxides, utilizing hypervalent iodine salts as the arylation reagents. The reaction was facilitated by visible light in conjunction with a photocatalyst. The absence of either the photocatalyst or light resulted in only trace amounts of the product, underscoring

• -donating groups. The reaction exhibited high selectivity, with substitution at the C3 position not impeding the reaction. Different substituted diaryliodonium tetrafluoroborates were also investigated, yielding good product yields. The above protocol for the arylation of pyridine N-oxides 28, resulted in