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

• sustainable approaches. Given the widespread incorporation of the cinnamic acid framework in various therapeutic agents, this review delivers critical insights into a molecular design for hit-to-lead optimization, offering detailed synthetic strategies for diverse functional modifications. By critically

• examining these methodologies, the paper underscores their role in expanding the utility of cinnamic acid derivatives and addressing prevailing challenges. Keywords: biologically active; cinnamic acid derivatives; environmentally sustainable; synthetic methodologies; Review 1 Introduction Cinnamic acid is

• applications in the pharmaceutical industry. In addition, innovative synthetic methodologies, including environmentally sustainable approaches [21][22][23], advanced catalytic systems [24][25][26], photocatalysis [27][28][29], and cutting-edge technologies, such as flow chemistry [30][31], have contributed

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• biocompatibility. The electrochemical properties of such materials have been then evaluated by cyclic voltammetry (CV). For all the properties mentioned above, CDs emerged as low-cost and sustainable photocatalysts. Indeed, upon visible-light irradiation, the generated excited state CD* can operate as either

• types of CDs and aims to promote the use of these sustainable materials, it opens the way for further exploitation of such compounds in visible-light-catalyzed reactions. UV–vis spectra of the CDs. All the measurements have been performed in water, except for CD-a-GLU, where a H2O/acetonitrile 1:1

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

• providing illustrative examples across reaction classes, and emerging strategies for programming synthetic outcomes. The integration of these approaches promises to accelerate drug discovery and materials development through sustainable, atom-economic synthesis of complex molecular libraries. Review Ligand

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

• recent years on developing new methods for synthesizing organophosphorus compounds [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Developing sustainable and green methods for synthesizing organophosphorus materials is a growing field. Methods based on photocatalysis [36], flow-based

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• from a brief Web of Science analysis of the 6,700 articles, published within the past 25 years, retrieved through a search of the keywords “asymmetric organocatalysis”. Organocatalysis is now part of various areas of chemistry, spanning as far as polymer, materials, as well as green and sustainable

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• this study, we present an innovative, sustainable approach to synthesizing hydantoins (H2a–j) directly from amino acids. This method employs a column chromatography-free, two-step, one-pot microwave-assisted synthesis that delivers hydantoins in yields ranging from 34% to 89%. The protocol demonstrates

• significantly speeds up reaction times, making it a valuable advancement in green and sustainable chemistry. Experimental General procedure for the synthesis of (S)-5-benzylimidazolidine-2,4-dione (H2a) A 30 mL microwave reactor vial was charged with ʟ-phenylalanine (5 mmol), distilled water (7 mL), and

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• concerns and improved reaction control can be addressed, paving the way for more efficient and sustainable synthetic methodologies. Keywords: cascade reactions; formaldehyde surrogates; green chemistry; heterocycles; multicomponent reactions; Introduction Organic chemistry is a mature discipline that has

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• compounds is a significant and important reaction for the selective synthesis of homoallylic alcohols in an efficient and sustainable way [2][3]. As carbonyl compounds, alkyl trifluoropyruvates [4][5] are an interesting class of compounds that have been used in addition reactions of different nucleophiles

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

• solvent. Mechanochemical synthesis, particularly through ball milling, has emerged as a powerful and sustainable technique that offers numerous advantages over traditional solution-phase methods [40][41][42]. By often eliminating the need for solvents, mechanochemistry reduces environmental impact and

• photons and forces, streamlining the combination of mechanochemical and photochemical processes and paving the way for more efficient, sustainable, and selective transformations in organic synthesis. An unexplored opportunity is offered by resonant acoustic mixing (RAM) [82], a technology that leverages

• provide highly sustainable approaches for synthesis, we envision a powerful synergy between these fields. In fact, we provide a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis for the strategic development of this new exciting field (Figure 3). By combining their knowledge, researchers

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

• been inspired to understand and mimic these accelerations and selectivities for applications in catalysis for sustainable synthesis. Over the past 60+ years, mimicry strategies have evolved with changing interests, understanding, and synthetic advances but, ubiquitously, research has focused on use of

• of increasing importance in the search for sustainable feedstocks, and cages that organize and polarize have advantages in this precise reactivity. The need for polarization may be circumvented by incorporating photocatalysts into cages [183][429], which are also likely to provide novel site

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

• become a powerful approach for achieving sustainable chemical transformations, combining high efficiency with energy-saving, mild conditions. By harnessing the deeper penetration and selectivity of red and near-infrared light, this method minimizes the side reactions typical of higher-energy sources

• sustainable photocatalysis, with applications ranging from selective oxidation to cross-dehydrogenative coupling. These organic systems are valued for their reduced environmental impact, their wide availability, and tunability, making them viable alternatives to traditional metal-based catalysts for red-light

• transition-metal catalysis. As the use of osmium catalysts has already demonstrated scalability in industrial applications [22], the introduction of bismuthinidene complexes presents another step forward in expanding the photoredox catalysis toolkit, potentially paving the way for more sustainable and

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• of our ongoing interest in radical cyclization reactions [22][23][24][25][26], we report here a sustainable and efficient protocol for synthesizing difluoromethylated and aryldifluoromethylated polycyclic imidazoles via visible-light-promoted cyclization of unactivated alkene-containing imidazoles

• difluoroacetate anion. Conclusion In summary, we have successfully developed a sustainable and efficient method for synthesizing difluoromethylated and aryldifluoromethylated polycyclic imidazoles through visible-light-promoted radical reactions. In contrast to previous reports, we achieved high yields of

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• temperature and severe weather patterns – a result of human-induced greenhouse gas emissions. The principle of net-zero revolves around the idea of using Earth’s carbon resources at a rate that does not exceed their natural replenishment. In 2015, the United Nations introduced the Sustainable Development

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• increasing interest as affordable, versatile, and sustainable catalytic systems. These catalysts are extensively employed in organic synthesis owing to their cost-effectiveness, reduced toxicity, and natural abundance [20][21][22][23][24][25][26][27][28]. The use of copper salts has enabled a variety of

• ][58][59][60][61], and photoinduced alkylations of various nucleophiles [22][62][63][64][65][66][67][68]. Recently, these sustainable catalytic systems have gradually been applied to amidations employing dioxazolones as amide sources. To the best of our knowledge, no review article has yet covered the

• recent progress in the chemical transformation of dioxazolones using copper salts. This review provides an overview of the recent achievements in the use of copper salts as sustainable metal systems for the transformation of dioxazolones. This review also discusses several related proposed mechanisms

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

• Yemin Kim Won Jun Jang Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Korea 10.3762/bjoc.21.9 Abstract In recent decades, organic electrosynthesis has emerged as a practical, sustainable, and efficient approach that facilitates valuable transformations in synthetic

• chemistry. Combining electrochemistry with transition-metal catalysis is a promising and rapidly growing methodology for effectively forming challenging C–C and C–heteroatom bonds in complex molecules in a sustainable manner. In this review, we summarize the recent advances in the combination of

• electrochemistry and copper catalysis for various organic transformations. Keywords: copper; electrochemistry; radical chemistry; single-electron transfer; sustainable catalysis; Introduction Transition-metal-catalyzed cross-coupling has emerged as an effective method for forming carbon–carbon (C–C) and carbon

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

• type of reaction. Review Three-component reactions Several three-component procedures have been successfully carried out using Cu(OTf)2 as a catalyst. These processes have been exploited mainly to access nitrogen compounds endowed with various structures, in a faster and more sustainable way than

• , secondary aliphatic or aromatic amines and thiols in the presence of catalytic Cu(OTf)2 (1 mol %) in aqueous media was proven to be a sustainable procedure to access thioaminals 5, avoiding high temperatures and/or hazardous reagents required by classical conditions (Scheme 4) [18]. The 1,2

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

• , differing from established isolation and separation techniques, holds the promise of not only enhancing the efficiency of HTE flow synthesis but also paving the way for more sustainable growth in this research area. Autonomous self-optimizing flow reactors Autonomous self-optimizing flow reactors (ASFRs

• energy consumption and reduced use of hazardous materials, contributing to more sustainable chemical processes. Integrating ML algorithms to simultaneously optimize multiple parameters such as yield, purity, and cost within a closed-loop represents a significant advancement in process design. Furthermore

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

• rapid generation of chemical libraries with high diversity in a time-efficient and environmentally sustainable manner. In this review, we focus on central nervous system (CNS) disorders, particularly Alzheimer's disease, Parkinson's disease, schizophrenia, depression, and epilepsy, where MCRs have

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• ; Sonogashira–Hagihara coupling; Introduction The application of sustainable energy storage and supply has become a very important issue both from an economic and ecological point of view. In particular, the global energy demand is continuously expanding because of the increasing population, the development of

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• various transformations [54][55][56][57][58][59][60][61][62][63][64]. In consequence, a large number of transition-metal-catalyzed or radical-mediated processes for C–H functionalization of aldehyde hydrazones has flourished over the years. An ideal scenario for a direct and sustainable synthetic route

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

• -value oxazolidinones with exceptional yields and enantioselectivities. This not only addresses the challenge of CO2 waste but also opens new avenues for the sustainable synthesis of complex molecules. Comprehensive mechanistic investigations underscored the pivotal role of DABCO in promoting CO2 capture

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• aromatic substitution giving the final spiro-indolenine. The scope of the process has been investigated with respect to all three components. Simple operations, mild conditions, and good yields make this strategy a convenient and sustainable way to obtain novel spiro-indolenine derivatives. Keywords

Young investigators in natural products chemistry, biosynthesis, and enzymology

• Jeffrey D. Rudolf,
• Lena Barra and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 2720–2721, doi:10.3762/bjoc.20.229

• Jeffrey D. Rudolf Lena Barra Takayoshi Awakawa Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA Fachbereich Chemie, Universität Konstanz, Universitätsstraße 10, 78464 Konstanz, Germany RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• catalyst efficiency and selectivity in sustainable chemistry applications. Keywords: asymmetric catalysis; carbon dioxide; CO2; epoxide; frustrated Lewis pairs (FLPs); volcano plot; Introduction The field of frustrated Lewis pairs (FLPs) has flourished since their seminal discovery in 2006 by Stephan and

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