The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• solvent medium for the reaction, and the related compounds were obtained through straightforward isolation techniques in a relatively short time frame (5–80 minutes). A comprehensive investigation was conducted utilizing various web platforms, encompassing ecological and environmental risk assessments

• cylinder chart in Figure 7. Indeed, a significant proportion of the experimentally measured Green Chemistry parameters for methyl laurate are consistent with the predictions of various software or web platforms, and in some cases, even demonstrate that certain toxicity parameters of methyl laurate are more

Adaptive experimentation and optimization in organic chemistry

• Artur M. Schweidtmann and
• Philippe Schwaller

Beilstein J. Org. Chem. 2025, 21, 2367–2368, doi:10.3762/bjoc.21.180

• have enabled this transformation. High-throughput experimentation platforms can now rapidly test large numbers of reaction conditions [3]. Machine learning algorithms can process complex chemical data to identify promising directions [4]. Closed-loop systems can autonomously design, execute, and

• approaches across multiple areas. Quijano Velasco et al. review recent advances in high-throughput automated chemical reaction platforms and machine learning algorithms for reaction optimization, showing how these approaches reduce experimentation time and human intervention [8]. They also discuss current

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• [14][15]. In recent years, the chiral biomass derivatives levoglucosenone (LGO, 5) and its reduced form Cyrene® (6) have gained increased attention as platforms for drug discovery [16][17][18][19]. The bicyclic ketone 5 is the major product from the pyrolysis of acid-treated cellulose [20], while its

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• : aldehydes; biobased chemistry; biomass; carbonyl; fine chemicals; ketones; multicomponent; platforms; sustainability; Introduction Shifting towards sustainable practices in the chemical industry relies on continued advancement of green chemistry sciences which aim to minimize the global environmental

• , and illustrating their high-value conversion methods towards fine chemicals. Review C2 biobased carbonyl platforms Glycolaldehyde Developing accesses from biomass to structures such as glycolic acid (GA) and glycolaldehyde (GCA) with high atomic economy is challenging. Hu et al. reported a new route

• single ion catalyst, Brückner and Shi synthesized value added formamides by treating amines with different C2 and C3 platform molecules like GA, glyceraldehyde (GLAD), and 1,3- dihydroxyacetone (DHA) (Scheme 9) [37]. C3 biobased carbonyl platforms Lactic acid (LA) Propanoic (or propionic) acid (PA), a

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• asymmetric Mannich reactions, the past two decades have witnessed the remarkable evolution of CPA catalysis into one of the most versatile platforms for achieving diverse enantioselective transformations [3][4][5][6][7][8]. CPA catalysts are generally recognized as bifunctional catalysts with two distinct

• molecular platforms in various applications, such as circularly polarized luminescence (CPL) materials, chiral liquid crystals and asymmetric catalysis. Currently, the asymmetric catalytic synthesis of helicenes predominantly revolves around transition metal-catalyzed asymmetric annulation reactions

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• 30 minutes at a pH of 5.5, which simulates the lysosomal environment at 37 °C. Both CAs and PAs are effective supramolecular platforms for the controlled release of DOX, demonstrating significant potential for various applications. In 2013, Wang and others reported [93] that WP6 and hydrophobic

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• early as the 1970s [10]. However, these remained largely isolated cases – more mechanistic curiosities than general synthetic platforms. The narrative shifted significantly in the late 2000s, when interest in early pioneering work on photocatalysis was revisited, and systematic investigations began to

• Review article discussing photocatalysts capable of harnessing low-energy red light to trigger chemical reactions [19]. In addition to photoredox catalysis, several mechanistic platforms that leverage light – such as the use of electron donor–acceptor complexes [20], proton-coupled electron transfer [21

• thematic issue that visible light increases the reaction rate of palladium-catalyzed Negishi cross-couplings [34]. The integration of enabling technologies has also contributed to the success of photocatalytic organic synthesis [35]. Automated reaction platforms, high-throughput experimentation techniques

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• large Stokes shift (85 nm) with emission at 530 nm in DMSO [23] (Table 2). Collectively, these studies underscore the structural versatility and functional tunability of heterohelicenes, establishing them as robust platforms for advanced chiral optoelectronic materials. Their diverse response to

• , thereby advancing their application in multifunctional chiral photonic and sensing platforms. In 2025, Gryko’s group synthesized a series of heterohelicenes 34a–c, featuring a 1,4-dihydropyrrolo[3,2-b]pyrrole (DHPP) core [48] (Table 10). The compounds exhibit similar absorption and emission profiles

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• phenacene molecules are quite robust against an oxidative environment even under photoillumination, they are considered to be promising platforms for constructing practical organic functional molecules. Recently, fluorinated PAHs attracted considerable attention because the introduction of fluorine atoms

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

• intervention. Herein, we review the currently used state-of-the-art high-throughput automated chemical reaction platforms and machine learning algorithms that drive the optimization of chemical reactions, highlighting the limitations and future opportunities of this new field of research. Keywords: autonomous

• consonant and/or conflicting targets. In addition, the incorporation of lab robotics into chemical synthesis has enabled the development of closed-loop optimization platforms capable of executing optimization campaigns rapidly with minimal human intervention, relieving experimenters from labor-intensive

• review follows the steps presented in Figure 1. In the following section, we review the high-throughput platforms currently used to perform chemical reaction optimization. Thereafter, we discuss the development and use of analytical tools and data processing algorithms. After that, we discuss the latest

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• platforms, we herein present a photo-flow platform for Achmatowicz reactions. A novel photo-flow solar panel reactor was fabricated to test and validate the Achmatowicz rearrangement reaction (Figure S1, Supporting Information File 1), and the reaction conditions were optimized with a ruthenium catalyst. As

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• , pressure, and solvent choice, thus it polishes and trims the suggested routes. As a result, CASP tools have attracted commercial interest and stimulated the development of integrated robotic platforms for automated flow synthesis [9][10][11]. However, as Coley et al. [12] pointed out, there are still

• ], and reaction conditions optimization [13]. These techniques have also been integrated with robotic platforms to speed up the discovery and synthesis of new materials and drug candidates, showcasing the potential and promising benefits of self-driving chemistry labs [19]. Raghavan et al. [20] compared

• requires sufficient and diverse reaction data for training, so that the models can have broader applicability and usefulness for CASP in autonomous robotic platforms [12][21]. On the other hand, the local models focus on a single reaction type. Generally, more fine-grained levels of experimental conditions

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• , thus providing an efficient guide to optimize reaction conditions [12]. Taylor et al. [13] and Bures et al. [14] have performed kinetic modeling with data collected from continuous flow systems with automated platforms. Yao et al. constructed a kinetic model on thermal dissociation and oligomerization

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• comprehensively in several reviews [45][46][47][48]. Applications of cleavable linkers, which might be considered as pioneers of MS fragmentation-based platforms to search peptide-linker remainders, were reviewed thoroughly as well [49][50][51]. Recent advances in mass spectrometers technology and analysis

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• . With HTE platforms established and due to their importance to ML campaigns, the past few years have seen a trend in creating larger experimental chemical reactivity datasets, in particular for transition metal catalysis [47][48]. 2.2 Increasing data availability in ML for organocatalysis While, to the

Finding the most potent compounds using active learning on molecular pairs

• Zachary Fralish and
• Daniel Reker

Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185

• during medicinal chemistry projects. We believe that ActiveDelta and other pairwise approaches show particular promise for adaptive machine learning when training data hungry neural networks on limited data and can serve as accurate platforms to guide lead optimization and prioritization during drug

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• -ones (spirocarbamates). These spiro heterocycles are commonly obtained in good yields through treatment with triphosgene and DIPEA. In the last decade, Poirier’s group reported a synthetic strategy to produce several spiro derivatives as discovery platforms for new bioactive compounds (Scheme 20) [39

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• ]. Absorption correction was conducted with the multi-scan method in SADABAS software (APEX3 system) [52]. The structures were solved with directed methods in ShelxS [53] and refined with full-matrix least-square in ShelxL [53], implemented in WinGX [54] and ShelxLE [55] platforms. Non-hydrogen atoms were

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• functionalization of optically active polymers [106]. Theato and co-workers introduced vinyl/alkyne-bearing poly(vinyl ether)s [107], poly(vinylcyclopropanes) [108], and poly(allyl 2-ylideneacetate) [109] as promising new platforms compatible to thiol–ene chemistry. Atom transfer radical addition (ATRA) is another

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• first efforts in this direction [32][33]. Finally, both techniques are amenable to large-scale synthesis and ideally integrated with state-of-the-art reactor technology platforms, such as continuous flow reactors and high throughput screening plates. Various examples of scalability will be highlighted

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

•  4). Results and Discussion It is known that [e]-fused 1H-pyrrole-2,3-diones (FPDs) (Figure 2) are versatile synthetic platforms enabling the synthesis of numerous heterocyclic species [33][34][35][36]. They are polyelectrophilic compounds, bearing five electrophilic centers, whose reactivity

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• synthetic procedures applied to obtain a variety of insect pheromones. The present report summarizes the recent progresses made in insect sex pheromone synthetic applications in our group, with a particular focus on the quest for non-toxic and sustainable catalytic platforms developed in the iron-catalyzed

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• platforms [66], the group considered a system in which a photoexcited catalyst oxidatively cleaves a siloxycyclopropane with endo selectivity [67], leading to aryl–nickel capture and reductive elimination. Thus, when substrates 121 and 122 were photoirradiated with blue LED light at 45 °C in the presence of

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• presented a detailed review on continuous crystallizations of pharmaceutical compounds which discusses these approaches [108]. It is in the field of crystallization where the biggest gap between industry and academia is visible. While industry has large downstream platforms to purify APIs, academia is at a

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• identify currently overlooked BGCs Genome mining was pivotal for the expansion of NP chemical space in the past two decades. Despite the development of more and more sophisticated genome mining platforms, in many cases where truly novel NP scaffolds were described, the NP was isolated first and only then

• primary or secondary metabolism (both ends of the spectrum) are identified using the strategies listed below the bar and subsequently excluded from further analysis. gcBGC aims at identifying as-of-yet overlooked BGCs that cannot be detected by state-of-the-art bioinformatic platforms, here referred to as