A cascade synthesis of 2-aminothiochromones from 2-fluorophenyl ketone and thiocarbonyldiimidazole

• Kai Zhang,
• Haofan Shao,
• Kangjun Liao,
• Ying Xu,
• Shimei Du,
• Yanfang Zhao,
• Gang Li,
• Wenzhen Xu,
• Haihong Huang and
• Peng Li

Beilstein J. Org. Chem. 2026, 22, 1151–1159, doi:10.3762/bjoc.22.92

• Tuberculosis Prevention and Control, Beijing 100050, P. R. China State Key Laboratory of Digestive Health, Beijing, 100050, P. R. China 10.3762/bjoc.22.92 Abstract A highly efficient cascade synthesis of various substituted 2-aminothiochromones was developed. The commercially available thiocarbonyldiimidazole

• provides concise access to various 2-aminothiochromones in good to excellent yields (up to 94%). Keywords: cascade synthesis; TCDI; thiochromone; Introduction Sulfur-containing motifs are particularly important owing to their widespread applications and diverse biological activities [1]. As isosteric

• functionalization in a cascade synthesis mode, wherein TCDI not only serves as a source of sulfur, but also provides an imidazole that acts as a reactive handle for further functionalization, thus maximizing atomic economy. Herein, we disclose a cascade synthesis of 2-aminothiochromone with a highly flexible

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• gold complex and the silver salt, to efficiently achieve the 6-endo cyclization and subsequent conversions. During the development of this cascade synthesis process, we serendipitously discovered the involvement of a sky-blue fluorescent transient intermediate 18 (Figure 2). We therefore investigated

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

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

• Ganesher [57] reported the one-pot cascade synthesis of indole-imidazo[1,2,a]pyridine hybrids 61 (Scheme 23). In this study, the convertible isocyanide 1-isocyano-2-(2,2-dimethoxyethyl)benzene (59, Kobayashi–Wessjohann isocyanide) was utilized as one of the precursors in the GBB reaction. The acetal

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

• scaffolds Burroughs et al. developed an intramolecular Cannizzaro-based cascade synthesis for the construction of 8-membered cycloocta-2,5-dienones [91]. The initial formation of the organolithium species 82 formed by acetylide addition to the ortho-substituted bromoaldehyde 81, was subjected to halogen

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• reaction with AMP (via ADP) to ATP (2.5% AMP/27.5% ADP/70% ATP) [16]. In theory, the addition of another, ideally irreversible reaction can be used to pull the equilibrium further to the product side. Another recent application of PPKs in the cascade synthesis of cladribine triphosphate (2-chloro-2

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• . Finally, the residue was purified by distillation to give pure product 3b in 64% yield (1.05 g). Cascade synthesis of 5 via two-phase ring closing of 3b and following substitution with benzenethiol 4 in the presence of K2CO3 (Scheme 4). To a 100 mL flask were added 2b (4.0 mmol), CH3CN (4 mL), H2O (16 mL

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• cascade synthesis of hydrocoumarin 78 mediated by squaramide catalyst with 9-amino-9-deoxy-epi-quinine moiety 73 was reported by Albrecht et al. [59]. In this transformation, the authors developed a Michael addition of azlactones to 2-hydroxychalcones 76 followed by the opening of the azlactone 77 ring to

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• of magnesium ions on metabolic transformations of nucleosides [45], in particular on the phosphorylation of the primary hydroxy group of pentoses, catalyzed by ribokinases [46], as well as on the cascade synthesis of nucleosides starting from pentoses [47][48][49][50] has been described. Based on the

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• for gold(III) chloride whose photoreduction to gold(I) was fast and controlled [44][45]. These gold complexes at different oxidation states showed efficient catalytic properties, that were highlighted in a one-pot cascade synthesis of 4H-benzoquinolizin-4-one. Now, we propose to investigate a rigid

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• phosphoribosyltransferase; catalysis; enzyme; hypoxanthine phosphoribosyltransferase; multi-enzyme cascade; nucleotides; thermophiles; Introduction Bacterial phosphoribosyltransferases are used in multi-enzymatic cascades that perform nucleotide synthesis de novo [1][2]. Recently, we reported on the possibility of cascade

• synthesis, where enzymes of thermophilic microorganisms Thermus thermophilus HB27 (phosphoribosylpyrophosphate synthetase – PRPPS and adenine phosphoribosyltransferase – APRT) and Thermus sp. 2.9 (ribokinase – RK) carry out successive transformations of ribose and adenine heterocyclic bases into the

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• development of heterogeneous Pd catalysts that are ready to be used in combination with biocatalysts for catalytic cascade synthesis of active pharmaceutical ingredients (APIs). In particular, we focus on the application of the catalytic systems for Suzuki–Miyaura cross-coupling reactions, which is the key

Scope and limitations of a DMF bio-alternative within Sonogashira cross-coupling and Cacchi-type annulation

• Kirsty L. Wilson,
• Alan R. Kennedy,
• Jane Murray,
• Ben Greatrex,
• Craig Jamieson and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2016, 12, 2005–2011, doi:10.3762/bjoc.12.187

• alternative to DMF, Cyrene. In addition, we have shown the capacity for extension of the utility of this new solvent towards enabling the cascade synthesis of functionalised indoles and benzofurans via a Cacchi-type annulation. Perhaps more importantly, we have documented some of the limitations of the use of

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates

• Hong-Bo Zhang,
• Yong-Chun Luo,
• Xiu-Qin Hu,
• Yong-Min Liang and
• Peng-Fei Xu

Beilstein J. Org. Chem. 2016, 12, 253–259, doi:10.3762/bjoc.12.27

• generated through multicomponent quadruple cascade reactions, there is no report about the cascade synthesis of isoindolines in the past few decades [35][36][37][38][39][40][41][42][43][44][45][46], not mention the quadruple cascade synthesis of difficult fully-substituted hexahydroisoindolinones

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• synthesis of quinazolinones via methyl C–H bond amidation. Dicumyl peroxide-based cascade synthesis of quinazolinones. Copper-catalyzed cascade reactions for the synthesis of indolinones. Acknowledgements The authors thank the Natural and Science Foundation of China (no. 21562025) and Natural and Science

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• alkenes via C–H cleavage is much less known in literature. In 2014, Yu and co-workers [66] reported the cascade synthesis of functionalized pyrrolones 66 via the dual C–H functionalization of α-alkenoylketene N,S-acetals 65. The construction of the products involved the oxidative alkene C–H amination and

• of bromoindolizines. Copper-mediated C–H halogenation of azacalix[1]arene[3]pyridines. Copper-mediated cascade synthesis of halogenated pyrrolones. Copper-mediated alkene C–H chlorination in spirothienooxindole. Copper-catalyzed remote C–H chlorination of alkyl hydroperoxides. Copper-catalyzed C–H

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• using the α-D-pentofuranose-1-phosphates as glycosylating agents. The cascade synthesis involves a sequential conversion of D-pentoses into their 5-monophosphates catalyzed by the recombinant E. coli ribokinase (RK; ATP co-factor) [27], stereospecific isomerization of the 5-phosphates into α-D

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• temperature (80 °C), but under an argon atmosphere [16]. An interesting Ag-promoted cascade synthesis of pyrrole-2-carboxyaldehydes involving an A3-coupling followed by an unusual imidazole ring opening, was reported by Liu in 2011 [17]. The authors found that propargylamines derived from the AgBF4-catalyzed

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• (10 mol %), DMF (3.0 mL), LiOt-Bu (2.00 mmol); yields of isolated product. a60 °C in the first step. Nonsequential cascade synthesis of fully substituted triazoles 4. General reaction conditions: 1 (1.00 mmol), 2 (1.00 mmol), NaN3 (1.05 mmol), CuI (10 mol %) DMF (3.0 mL), LiOt-Bu (2.00 mmol); yields

Efficient gold(I)/silver(I)-cocatalyzed cascade intermolecular N-Michael addition/intramolecular hydroalkylation of unactivated alkenes with α-ketones

• Ya-Ping Xiao,
• Xin-Yuan Liu and
• Chi-Ming Che

Beilstein J. Org. Chem. 2011, 7, 1100–1107, doi:10.3762/bjoc.7.126

• . Some control experiments. The reaction pathway. The optimization of the reaction conditions. Screening catalysts and solvents. Cascade synthesis of pyrrolidine catalyzed by a dual-metal catalytic system comprising of gold(I) and silver(I) catalysts. Supporting Information Supporting Information File