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

• hydrogen-atom transfer or solvolysis are often observed. A technological solution to cope with the Beer–Lambert law was offered by flow chemistry [19][20][21] by employing microreactors with reduced optical paths to enhance irradiation efficiency [22][23][24]. Photon-limited reactions, whose efficiency is

• primarily constrained by the availability of photons in the reaction mixture, particularly benefit from this approach. Paradoxically, flow chemistry is a convenient technology to increase the productivity of photochemical reactions via numbering-up and sizing-up approaches [25], but it is highly dependent

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

• system comprised of a flow chemistry synthesis platform, a reagent delivery system, a packed bed reactor, process-analytical tools, and an integrated software control system that automates end-to-end process operations and monitoring. The system has been used to demonstrate the synthesis of at least ten

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• Perry van der Heide Michele Retini Fabiola Fanini Giovanni Piersanti Francesco Secci Daniele Mazzarella Timothy Noel Alberto Luridiana Department of Chemical and Geological Sciences, University of Cagliari, S.S. 554, bivio per Sestu, 09042 Monserrato (CA), Italy Flow Chemistry Group, Van ’t Hoff

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

• of ¹³¹I-labeled compounds. For example, the late-stage iodoamination of cytisine, amoxapine, and fluoxetine hydrochloride was achieved with yields of 65%, 87%, and 73%, respectively. Additionally, this transformation was successful for gram-scale synthesis via batch and flow chemistry, indicating

• C–H hydroxylation process by combining continuous flow chemistry and electrochemistry (Scheme 8) [16]. The surface modification of electrodes can lead to improved reactivity and selectivity. In this regard, Li and coworkers developed electron-deficient W2C nanocrystal-based electrodes to enhance the

• oxygenation of C–H bonds, thus providing a valuable tool for the functionalization of complex molecules. A combined photoelectrochemical transformation with flow chemistry was developed by the Noël group. The flow electrophotocatalysis (f-EPC) system using FeCl3 as photocatalyst accelerates the C(sp3)–H

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

• platform developed with an integrated system enabling a downstream process in a time and labor-efficient manner which facilitates the Achmatowicz rearrangement, resulting in a fast (10 min) formation of the dihydropyranone products. Keywords: Achmatowicz reaction; flow chemistry; furfuryl alcohols

• a result, developing an alternative strategy would be an attractive solution to address the limitations described above. Flow chemistry was chosen as the most attractive alternative for the photo-induced (visible light) Achmatowicz rearrangement to convert furfuryl alcohol scaffolds into

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

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• . Additionally, the selection of the appropriate solvent is critical. To mitigate diffusion limitation, it is important to ensure appropriate mixing and flow characteristics and adequate concentration of reactants and catalytic units. Flow chemistry can be easily combined with solid-supported organocatalysis

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• benzyltrimethylsilane derivatives as the donor molecule in the flow photoreactor to provide 1H-isochromene derivatives in higher yields in most cases than the batch reaction system. Keywords: 2-benzopyrylium; flow chemistry; isocromene; photochemical reaction; π-Lewis acidic metal; Introduction Flow chemistry has

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• ; flow chemistry; Negishi; on-DNA chemistry; Introduction DNA-encoded chemical library (DEL) technology is a powerful tool for hit identification [1][2]. DELs are chemically synthesized libraries in which every member is covalently attached to a unique DNA sequence serving as a molecular “barcode” [3

• with the Negishi cross-coupling step in a continuous flow manner [41][42][43]. Continuous flow chemistry offers superior control over reaction parameters compared to traditional batch methods. This approach leads to reproducible reactions, improved safety features, and it can facilitate high-throughput

• screening and rapid optimization [46][47]. Homogenous heating and mixing in flow reactors can lead to higher reaction rates and yields. In terms of photochemistry, continuous flow setups provide enhanced light irradiation as well [48][49]. These advantages make flow chemistry a powerful tool for chemical

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

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• Damiano Diprima Hannes Gemoets Stefano Bonciolini Koen Van Aken Ecosynth, Industrielaan 12, 9800 Deinze, Belgium Flow Chemistry Group, Van ’t Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands Creaflow, Industrielaan 12

• flow using the HANU flow reactor, indicating scalability and improving safety. Keywords: catalyst-free; flow chemistry; oxygen; photochemistry; sustainable oxidation; Introduction Oxidation reactions are widely used in the chemical industry, but are often problematic due to challenges with

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• temperature). Thus, despite the synthetic interest of the molecules that can be obtained, transfers to industry are difficult. In order to circumvent this drawback, we considered transposing these batch reactions to a flow chemistry process. In recent years, the use of continuous flow chemistry in organic

• the C3-alkylation of furfural in continuous flow With the optimized conditions in hand (Table 2, entry 6), we were interested in extending the scope of this furfural alkylation reaction using a flow chemistry process to other reactants. For this, after each reaction, an aliquot of the resulting

• possible to implement at the moment with our reactors. Conclusion In conclusion, we have developed a method for the direct 2-step Ru-catalyzed alkylation of the C3–H bond of furfural by flow chemistry, via the preinstallation in a fixed bed reactor of an ortho-directing imine group that can be easily

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• review [5]. It is clear from the already mentioned facts about the synthesis of Ts-β-CD (2), that neither of these methods is suitable for the flow chemistry process. Heterogeneous mixtures should be strictly avoided and pyridine is a toxic compound and should not be used in large-scale syntheses or

Modern flow chemistry – prospect and advantage

• Philipp Heretsch

Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3

• Philipp Heretsch Institute of Organic Chemistry, Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover, Germany 10.3762/bjoc.19.3 Keywords: flow chemistry; method development; reactor design; Organic chemistry has shaped modern society by fulfilling the basic needs for pharmaceuticals

• , agrochemicals, fragrances, and many more. Implementation of new and innovative technologies has played a vital role in this mission and has contributed to the opening of new research areas and to pushing the frontiers of existing ones. Among these new technologies, continuous flow chemistry has stepped on the

• chemicals. This has again led to improved scalability, higher purity of products, and eventually decreased manufacturing costs. From the undisputed role of continuous flow chemistry for process chemists, the advent of this technology in academic research laboratories, especially for method development and

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• Friedel–Crafts alkylation followed by an anodic oxidative cyclization yielded a defined set of cyclic iodonium salts in a highly substrate-dependent yield. Keywords: electrochemistry; flow chemistry; hypervalent compounds; iodine; oxidation; Introduction Hypervalent iodine compounds (HVI) are well

• oxidation of iodoarenes to form DIS by Wirth et al. (Scheme 1B) [39]. Herein, established conditions for synthesizing DIS were transferred into flow chemistry utilizing a model flow reactor with two platinum electrodes. Other recent examples include the generation of five-membered CDIS utilizing fluorinated

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

• of (−)-FR901483 (160) and (+)-TAN1251C (162, Gaunt). Divergent synthesis of bipolamines (Maimone). Flow chemistry divergency between aporphine and morphinandione alkaloids (Felpin). Divergent synthesis of pyrroloazocine natural products (Echavarren). Using TEMPO to stabilize radicals for the

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

• chemistry tools developed in academia. Keywords: flow synthesis; inline purification; process development; reaction telescoping; scale-up; Introduction Continuous flow chemistry is a mature and widely applied platform technology that exploits intrinsic advantages over batch processing such as better heat

• flexibility at low cost or exploit standardized flow reactor modules readily available from various vendors. The growing popularity of flow chemistry over the last two decades has led to many developments to streamline important chemical reactions, overcome limitations due to highly unstable intermediates

• that would otherwise be prohibitive or achieve readily scalable processes suitable for industrial applications [6][7][8][9]. In addition, flow chemistry has become the method of choice in modern research areas including photo- [10][11][12][13], electrochemistry [14][15][16], and biocatalysis [17][18

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• effect on an animal model of the disease. Then, past these two hurdles, the task of selecting a clinical candidate and produce up to tons of it is also a major endeavor that has been often overlooked by the academia. However, a noteworthy exception would be the recent flow chemistry developments in the

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• as a model system. The catalyst was shown to be stable, with a very low decrease of the yield (≈1% per day) during a continuous experiment over seven days, and to be effective for C–O arylations when carboxylic acids are used as nucleophile instead of sulfinates. Keywords: flow chemistry

• synthesis [3]. The adoption of flow chemistry ensured short photon path lengths and overcame issues related to scalability and productivity caused by the limited light penetration in large batch reactors (Lambert–Beer law), thereby making photocatalysis a promising option for industrially relevant processes

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• , which can lead to higher yields and purity [22]. Flow chemistry to prepare azobenzenes has been previously applied to the Cu-catalyzed synthesis of symmetric substituted AB derivatives [23][24]. However, non-symmetric substituted ABs are not accessible by this method in an efficient way. Herein, we

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• the main odor families “fruity”, “green”, “marine”, “floral”, “spicy”, “woody”, “ambery”, and “musky” and their use and importance for perfumery is briefly discussed. Keywords: flow chemistry; fragrances; odorants; scents; terpenes; Introduction The history of odorants goes back to ancient cultures

• synthesis of odorants is the only way to provide them in sufficient quantities when natural sources are rare, or their production is unethical as it is the case for ingredients obtained from animals such as musk or civet [9][10]. In recent years, flow chemistry has enriched organic synthesis as an enabling

• technology to realize reactions that are impossible in batch or to provide products in higher purity avoiding expensive purification procedures [11][12][13][14][15][16][17][18]. Given the superior heat-, mass-, and phototransfer in microreactors, flow chemistry has been outlined as a central tool for

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• chemistry, but also in medicine. Traditionally, inductive heating is used in industry, e.g., for heating large metallic objects including bending, bonding, and welding pipes. In addition, inductive heating has emerged as a partner for flow chemistry, both of which are enabling technologies for organic

• synthesis. This report reviews the combination of flow chemistry and inductive heating in industrial settings as well as academic research and demonstrates that the two technologies ideally complement each other. Keywords: catalysis; enabling technologies; flow chemistry; inductive heating; multistep

• mesoflow technology and indirect heating 3.1 Microwave-accelerated reactions under flow conditions Reactions that take 20 minutes or longer under classical batch conditions can be accelerated considerably under continuous flow conditions by rapid heating, because flow chemistry usually involves the use of

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• telescoping; Introduction The application of enabling technologies in chemistry has received a surge in interest in recent years [1][2][3][4]. At the forefront of this revolution has been the advent of flow chemistry and its increasing utility in synthetic chemistry [5][6][7][8]. This is largely driven by