A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• purposes. This study not only contributes to the expansion of accessible N-substituted DPP derivatives but also reveals that such transformations can be achieved with outstanding efficiency and environmental sensitivity by employing mild reaction conditions. Experimental Chemicals and instrumentation The

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• composite compared to the individual constituents tested separately. Solvent-free conditions afforded better yields than traditional solvents (water, toluene, DCM, EtOH, MeOH) and 12 adducts were synthetized in 84–96% yield. Finally, the catalyst was recycled six times with a slight decrease in efficiency

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• regio- and diastereocontrolled hydroxylation at C3, along with transposition of the double bond, to form the desired product 22 in approximately 20% yield with 50% conversion. To enhance efficiency of the enzymatic oxidation, Renata and co-workers conducted two approaches: homolog screening and enzyme

• , efficiency, and robustness of these biocatalysts are expected to enhance their usefulness and generality as synthetic tools. Apart from oxygenated terpenes and RiPPs, chemo-enzymatic approaches for polyketides and non-ribosomal peptides (NRPs) are considered more suitable for the second and third strategies

• novel paradigm for exploiting the inherent specificity and efficiency of enzymatic catalysts within synthetic sequences. The integration of designed substrate analogs that can be transformed by promiscuous enzymes provides a versatile synthetic platform towards natural products and their derivatives. In

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• starting from α-bromoacetophenones 4 and disubstituted amines 5 (Scheme 2b). Three different criteria were chosen to evaluate the photochemical cyclization (Scheme 2c). We hypothesized that changes in the π-system of the aromatic ring would have an impact on the efficiency of triplet generation (1 → 31

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• advance and are not recycled in the system. The amino acids are methylated either prior to tRNA binding or after. The efficiency of incorporating unnatural amino acids is lower, but Merryman and Green have demonstrated that an excess of tRNA can overcome this problem [47]. When attempting to incorporate

• system and must be prepared beforehand. The incorporation of unnatural amino acids by the ribosome is less efficient and leads to incomplete translation, resulting in shunt products. Additionally, ribosome recycling efficiency and synthesis of full length proteins declines with length of the primary

• with N-terminal alanine, serine, threonine, glycine, and methionine residues, as well as the antibiotics nisin and haloduracin with good efficiency. Nisin was methylated on its N-terminal isoleucine and on the side chain of Lys12, where two methylations occurred. It is important to note that N

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• structural properties of the membranes restrain their stability and durability, their humidity and temperature application conditions, and their efficiency and consequently, the performance of fuel cells or eletrolysers [18][19]. Many organic polymers with acidic functional groups have been developed as

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• aromatic aldehydes (e.g., 2{1–3}) did not work in the GBB reaction (Figure 4). This result is in accordance with the previous findings [21]. Notably, steric effects were not significant since o,o′-disubstituted aldehydes (e.g., 2{4–6}) displayed usual efficiency. As might be expected from our previous

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• ), the charge for screening was set to 2.0 F mol−1 for rapid evaluation, and several cathode catalysts were examined. When Pd/C was used as the cathode, the reaction did not proceed (Table 3, entry 1). The desired reduction proceeded with Ru/C and 5a was obtained in 79% of current efficiency (Table 3

• , entry 2). Pt/C afforded the best result (90% current efficiency, Table 3, entry 3). To increase the yield, the reaction was carried out until 4a was consumed. After 7 h of electrolysis (23.2 F mol−1), 4a was completely consumed and 5a was obtained in 82% yield. Although Ir/C was inefficient (Table 3

• , entry 4), Rh/C was as efficient as Pt/C (Table 3, entry 5). As Rh is more expensive than Pt, Pt/C was selected as the best cathode catalyst. Although 5a was obtained in good yield with Pt/C, the current efficiency was low. We assumed that this was due to the recombination of Had to form hydrogen. To

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• on the arene were unsuccessful. Without substituents on the ring, aryl C–H activation and subsequent C–O bond formation occurred along with benzylic fluorination (7) (low efficiency). The presence of a p-methoxy group resulted in a switch in selectivity to acyloxylation 8’ as the major product. The

• -oxidation and decomposition to improve the reaction efficiency overall. Conclusion The fluorination of benzylic C(sp3)–H bonds provides rapid access to an important functional group used in medicinal chemistry to control the pharmacokinetic profile of drug candidates. Historical and recent research efforts

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• efficiency. Results and Discussion Our study of this new electrophotochemical metal-catalyzed decarboxylative cyanation commenced with the evaluation of various combinations of Ce and Cu catalysts. A simple undivided cell using a carbon felt, inexpensive and practical porous material as the anode, and a Pt

• -known to be highly susceptible to electroplating on the cathode and thus require the use of ligands to avoid detrimental cathode deposition during electrolysis (Table 1, entry 3). In addition, we discovered that the additional use of DMF as co-solvent is beneficial to the reaction efficiency–reactions

• , the corresponding alkylnitrile product was obtained in 86% yield after electrolysis at 3.0 mA for 4 hours, demonstrating the high Faradaic efficiency of the reaction (Table 1, entry 5) [46]. Control experiments revealed that Ce catalyst, Cu catalyst, light, and electricity were all essential for the

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• . Depending on the corresponding galactosyl azobenzenes, the Z-isomer is pure from 87 to 99%. Spectroscopy measurements were performed on ligand solution just before each experiment to check the efficiency of the isomerization, with results as indicated in Table 2. In all experiments, strong exothermic peaks

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• -benzylidenecyclohex-3-en-1-one (2a) and 4-methoxybenzylamine (3a) as starting materials to investigate the feasibility and efficiency of the reaction (Table 1). Initially, the reaction was conducted in the presence of 2.0 equiv of 3a in toluene at 60 °C without any addition of catalysts or additives. To our delight

• molecular sieves as water scavengers, but it showed no positive influence on the reaction efficiency (Table 1, entry 20). It should be noted that no competing aza-Michael adduct was monitored in all of the evaluated reaction conditions. According to the above screening results, the generality of the

• provides an alternative to the construction of anilines via an amination–aromatization strategy. Furthermore, it is also characterized by simple operation, mild reaction conditions, broad substrate scope and efficiency on a gram-scale preparation, thus allowing a new and convenient process to assemble

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• Jialiang Wu Haofeng Shi Xuemin Li Jiaxin He Chen Zhang Fengxia Sun Yunfei Du Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China Hebei Research Center of Pharmaceutical and Chemical

• equiv) and PhICl2 (1 equiv) in THF at 0 °C under N2 atmosphere. To our delight, the desired thiocyanated product 2a was obtained in 68% yield (Table 1, entry 1). Encouraged by this result, we proceeded to investigate the other parameters that would possibly affect the efficiency of the reaction. First

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• ; machine learning; Introduction Hypervalent iodine reagents are increasingly gaining attention in the fields of organic synthesis and catalysis due to their environmental benefits, accessibility, and cost-efficiency [1][2][3][4][5][6][7][8][9][10][11]. Over the last three decades, a series of cyclic

• 209 heterolytic BDE data points. Taking homolytic BDE datasets as an example (Figure 4a), the distribution of this dataset is illustrated with key bond energy values normalized using min–max scaling. This approach ensures both data consistency and improves training efficiency. We used the GAT model as

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

• the reaction efficiency, we screened several additional parameters including solvents and concentration. In these cases, we found that while both acetonitrile and MeNO2 (0.25 M) were suitable solvents, other solvents in general afforded no product formation (Table 1, entries 2–6). Lower catalyst

• loading and longer reaction time did not improve the overall reaction efficiency (Table 1, entries 6–8). Furthermore, we evaluated several salt additives containing different counterions, and found that LiBF4 was the optimal additive (Table 1, entries 7, 9, and 10). The optimal conditions were shown in

• desired oxazoline products with reasonable yields (Figure 2, products 8–10). Heteroaromatic amides could also furnish the oxazolines 11 and 12 with good efficiency. Naphthaleneamide also generated the desired product 13, albeit with slightly lower efficiency. Interestingly, o- and m-methyl-substituted

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

• reaction's efficiency. Although the reactions of ethyl 3-azido-1H-pyrazole-4-carboxylate (19j) resulted in lower yields of the triazole products 21ja–jh compared to pyrazolyl azides 19a, 19e, and 19o, this trend is not continued in the results of the N-substituted carboxylate derivatives 19k–n. The effect of

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• furnishing the corresponding alcohol (D) and acid molecule (E). Review Modernization of the Cannizzaro reaction Researchers have always aimed to improve the efficiency, selectivity, and sustainability of reaction processes. The development of reagents, solvents, and application of modern technology frame the

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• synthesis [4][5][6][7][8][9]. In the context of sustainable catalysis, visible-light-mediated chemistry is becoming a prominent viable option for radical transformations in the synthesis of biologically useful compounds due to the energy efficiency and environmental friendliness [10][11]. Recently, the

• of novel synthetic strategies. It has expanded the scope of available synthetic methods and contributed to the synthesis of complex molecules with high efficiency and selectivity. Ongoing research in this field continues to explore new catalysts, photosensitizers, and reaction mechanisms to further

• of electron-rich phosphoranyl radicals, which were more prone to oxidation before undergoing β-scission. The deoxygenation process of secondary benzylic alcohols occurred with decreased efficiency (i.e., 62m and 62n, 30 and 47%), in line with the slower addition of a more sterically hindered alcohol

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• high regioselectivity. Herein, we report the electroreductive hydroarylation of electron-deficient alkenes and styrene derivatives using (hetero)aryl halides under mild reaction conditions. Notably, the present hydroarylation proceeded with high efficiency under transition-metal-catalyst-free

• versatile building blocks in organic syntheses. To achieve this transformation with high efficiency and predictable regioselectivity, numerous efforts have been made to develop transition-metal-catalyzed reactions based on a C–H activation strategy [1][2][3][4] or the reductive coupling of aryl halides with

• extensive efforts to screen the reaction parameters to achieve the desired transformation with high efficiency, we found that the electroreductive coupling of 1a with 2a proceeded smoothly to afford 3aa in 82% yield under the conditions using an undivided cell equipped with Al(+)/Pt(−) electrodes in the

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• transporters [9][10]. Organic photovoltaic (OPV) and perovskite solar cell (PSC) technologies have proven to be promising candidates for the sustainable use of solar energy, with power conversion efficiency (PCE) improving to 17% for OPVs and over 25% for PSCs in just a few years [11]. Functionalized fullerene

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• solution of Aza-H with a lower concentration of TsNa (200 µM). We presumed this would enable us to exclusively monitor Aza-H•+ quenching by TsNa, since any triplet Aza-H would be deactivated by oxygen (see above). The ionization efficiency of Aza-H exhibits a quadratic dependence on the laser intensity

• of magnitude slower than the diffusion limit in MeCN, the long triplet lifetime ensures a quenching efficiency of 85% when a concentration of 200 mM cinnamyl chloride is used. Exposed to 427 nm irradiation with 1 mol % Aza-H 41% of the chlorocyclopropane and 50% of the branched allylic chloride was

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• -acetamide carboxamide oxindole hybrids 5 was obtained in moderate yields (26–63%), at room temperature, in short time (2 hours), proving the efficiency and the generality of this methodology. Aliphatic (2a, 2c and 2m), aromatic (2d, 2f, 2g, 2k and 2l), heterocyclic (2e, 2h, 2i, 2n and 2o), alkyne 2b and

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• correlates with the trend reported for CDA inhibitors [47][51]. We also demonstrated that IIc- and IId-containing DNAs also inhibit full-length wild-type A3G with similar efficiency to that for the single catalytically active CTD [57][58]. Recently, analysis of crystal structures revealed that both dZ (IIc

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• redox couple NaBr–NaBrO3 in acidic media [40][41]. Other variations include the system KBr–Oxone® [42]. However, based on a literature review, we concluded that unparalleled efficiency and sustainability can be achieved through the well-established redox equilibria between hydrogen peroxide and halide

• [46][47][48][49], which can be produced with high efficiency. The peroxide-bromide method appears to be especially suitable for obtaining aryl-cored dibromides, too. However, to the best of our knowledge, this option has been scarcely exploited, except for a few reports on some activated arenes [50

• , both inferior to 4.5 (i.e. less than 4.5 kg of wastes to get 1 kg of product), denotes a good sustainability. Moreover, more than 2 kg of wastes come from losses in the recycle of CH2Cl2. Therefore, these results can be easily improved by increasing the efficiency of solvent recovery, here set at 85