Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• related biological branches (Scheme 2) [52]. Studer and his group efficiently developed a method to achieve the acylation of benzylic C(sp³)–H bonds via cooperative NHC and organophotocatalyzed dual catalysis. The key step in the reaction is a radical–radical cross-coupling process leading to the

• production of ketone scaffolds, including drug moieties. The organocatalyzed acylation proceeds with excellent site selectivity and broad functional group tolerance of alkanes such as F, Cl, Br, I, CN, CF3, Me, and OMe. The reaction was achieved between acyl fluoride 4 and highly substituted alkane 7 in the

• –H bond functionalization of important structural motifs with good to excellent diastereoselectivities, high yields, and late-stage functionalization of drugs and complex natural products. The visible-light-promoted dual catalytic method opens new avenues in direct C–H bond acylation and complements

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• ryanodine skeleton via an established single-electron reductive cyclization to complete the total synthesis. This strategic inversion of the synthetic sequence enabled direct acylation of anhydroryanodol derivatives, facilitating the introduction of the key pyrrole-2-carboxylate unit. This method

• alkyne difunctionalization, furyl group installation, Achmatowicz rearrangement, and subsequent functional group manipulations provided intermediates 84 and 85. C5-acylation and methylation under kinetically controlled conditions followed by Sonogashira coupling yielded cyclization precursor 89

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• addition of the acyl chloride to excess 9 was important to avoid forming bis-acylation of the phenylenediamine. The carboxylic acid 13 was formed using a microwave-promoted ring opening of glutaric anhydride (11) and benzyl-protected PNA backbone 12 [38]. A series of optimizations was performed in a

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• enantioselectivity. New catalytic methods have been developed by merging photoenzymatic catalysis with small-molecule photoredox catalysis. Enantioselective radical acylation reactions of N-hydroxyphthalimide esters and aldehydes, yielding α-substituted ketones, were catalyzed by a radical acyl transferase (an

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• Discussion Our degradation strategy of natural products bearing an MPO moiety includes (1) acylation of hydroxy group, (2) oxidative cleavage of olefin to generate 3-acyloxy-2-methylbutanoic acid, and (3) its methyl esterification (Scheme 1A). We initially investigated derivatization strategies to enable LC

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

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• methodologies from traditional acylation/carbamoylation [9] to advanced Pd- or Rh-catalyzed C–H activation [10][11], FeIII–CuII/p-TSA–CuI catalyzed ring expansion/cyclization [12], electrochemical C–H/N–H functionalization [13], RhIII-catalyzed C–H amidation [14], etc. In contrast to chemical studies, a

• (5) (Scheme 1), a structural analogue of the biologically active alkaloid tryptanthrin (Figure 1). An alternative scheme to indolo[1,2-c]quinazoline-12-carboxylic acid (3) was based on initial acylation followed by a haloform reaction. Refluxing compound 1 with trifluoroacetic anhydride (TFAA) in

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• biologically active molecules. Based on the reaction types, three strategies are discussed: enzymatic acylation, transition-metal-catalyzed acylation, and local desymmetrization. Keywords: asymmetric synthesis; desymmetrization; 1,3-diols; natural product; total synthesis; Introduction Natural products

• emphasis on the desymmetrization of diols. Prochiral 1,3-diols, as simple and practical substrates, have been widely used in developed desymmetrization methodologies with applications in the total synthesis of natural products and bioactive molecules, including enzymatic acylation, transition-metal

• -catalyzed acylation, and local desymmetrization. In this review, we cover total syntheses that utilize enantioselective desymmetrization of prochiral 1,3-diols. Review Desymmetrization via enzymatic acylation Enzymatic reactions represent one of the most useful tools in total synthesis. Through combination

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• bromide 47, followed by Fmoc protection of 56, Boc deprotection of 57, reduction of the NO2 group to NO and intramolecular Mills coupling to form 35h. Removal of the Fmoc protecting group under basic conditions affords the unsubstituted product 35d which, after N-alkylation or acylation affords the

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• hydrostatic pressure (HHP) was found to be an efficient activation method in several catalyst- and solvent-free reactions and has found application for the syntheses of heterocycles and the preparation of active pharmaceutical ingredients (APIs) via acylation and acid- and solvent-free esterification. The

• (Scheme 2). HHP-assisted acylation of NH and OH groups: synthesis of acetaminophen (paracetamol) and acetylsalicylic acid Tylenol® and Aspirin® are two popular drugs used as pain killers as well as antipyretics [45]. Although their industrial production is straightforward, these syntheses include the use

• illustrate that HHP provides some advantage in both reactions, more evident in the case of OH acylation. The NH2 acylation occurred much more rapidly in 10 s at room temperature, while also generating the product nearly quantitatively. The OH group is significantly less reactive under such conditions

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• ; condensation; Einhorn-type acylation; 2-methyl N-benzyl benzothiazolium salts; Introduction Aroyl-S,N-ketene acetals, in particular N-benzyl derivatives 1, are very short donor–acceptor chromophores that have recently found a renaissance due to their peculiar intense solid-state emission and significant turn

• presumed byproducts in the addition–elimination sequence in the presence of an excess of ethanol as a cosolvent are the ethyl ester formed by Einhorn acylation [7] of the acid chloride under the standard conditions and deep colored polar byproducts (according to TLC detection) that arise from self

• -condensation of 2-methylbenzothiazolium salts 7 and intermediary formed S,N-ketene acetals 4 at elevated temperatures. Einhorn acylation is governed by the electrophilicity of the acid chloride or acylammonium species and the nucleophilicity of any nucleophilic species present in the reaction mixture. In

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• -inflammatory [21][22] as well as enzyme inhibition activities [23][24][25][26]. Traditionally, β-ketophosphonates were prepared via Arbuzov reaction [27], acylation of alkylphosphonates [28], and hydration of alkynylphosphonates [29][30][31]. However, these methods have several drawbacks, including low atom

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• Ashutosh Nath John Mark Awad Wei Zhang Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA 10.3762/bjoc.21.92 Abstract A new synthetic route initiated with Groebke–Blackburn–Bienaymé (GBB) followed by N-acylation, intramolecular Diels–Alder

• compounds [18]. Presented in this paper is a new synthetic route involving GBB, N-acylation and IMDA reactions for making intermediate III followed by dehydrative re-aromatization to give imidazopyridine-fused isoquinolinones C (Scheme 1C). Results and Discussion Following the reported procedures [10], the

• step is energetically favorable. Other than furfural, thiophene-2-carbaldehyde (2s) was used for the GBB and N-acylation reactions to make 6t (Scheme 4). The IMDA reaction of 6t was carried out under the catalysis of AlCl3 in dichlorobenzene at 180 °C for up to 24 h, but no compounds 7t and 8t could be

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

• methodologies based on the functional groups of cinnamic acid reported in the last five years: modifying the carboxyl group can involve several pathways, such as O/N-acylation, oxidative acylation, alkenyl/alkynyl carboxylation, and other reactions. Altering the double bond can be approached through double-bond

• cinnamic acid (7) and N,N’-dimethylformamide (DMF)-mediated by POCl3 via acid chloride 36 formation (Scheme 20) [52]. On top of the carboxyl activation approaches demonstrated above, O/N-acylation could also be achieved by employing an electrophilic alkylating agent by exploiting the nucleophilicity of the

• cinnamic acid. For example, Chen and co-workers (2020) reported the Pd-catalyzed N-acylation of cinnamic acids using tertiary amines to generate the corresponding amides 83 and 84 in good yields via C–N cleavage (Scheme 25) [61]. The active Pd0 species was inserted into the carboxylate group to afford the

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• reaction with nucleophilic lithium amide from n-propylamine, the reduction of phosphine oxide 9 by trichlorosilane/triethylamine, and the N-acylation of 10 with cinnamoyl chloride in three steps (Scheme 1). We also analyzed amide compound 7 by HPLC analysis using a chiral stationary phase column with a CD

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• , probably due to the formation of a more acidic cationic gold complex. Following this annulation, reduction of the amide in 20, catalytic hydrogenation of the alkene and the N-benzyl group, and subsequent nitrogen acylation yielded chloride 21 in a 42% total yield, setting the stage for the Witkop

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• molecules could be synthesized from diol 9 through a late-stage modification involving adjustment of the oxidation state and regioselective acylation. The formation of 9 was envisioned to proceed via an intramolecular pinacol coupling [30][31] of [5,5,6,6]-tetracycle 10, which forges the A2 ring while

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• discovered that simple acylation of the pyrazole moiety leads to increased quantum yields of isomerization, long Z-isomer life-times, good spectral separation, and high photostability. Keywords: azobenzenes; azopyrazoles; photochromism; photoswitches; substituent effects; Introduction Organic photoswitches

• . Acylation of the pyrazole moiety led to an enhanced metastable half-life compared to the NH-PAPs. For NAc-PAP-H, we observed increased half-lifes (21.5 days, 30 °C), compared to the reported NH-PAP-H (0.066 days; 25 °C [51]) or NMe-PAP-H (10 days; 25 °C [31], all in CH3CN). In the presence of OH as

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• Massarilactones constitute a rare class of polyketides produced mainly by endophytic fungi. Given that semisynthetic derivatives often exhibit biological activities greater than those of the substrates, seven previously unreported derivatives of massarilactone D, compounds 2–8, were synthetized by acylation with

• nematicidal activity with LD90 and LD50 of 100 and 12.5 µg/mL, respectively. Since the parent compound was not active, the present study supports the fact that the acylation reaction can improve bioactivities of some natural products. Keywords: acylation reaction; cytotoxic activity; massarilactone D

• activity of this polyketide. Seven analogues of massarilactone D, compounds 2–8, were synthetized through acylation modifications aimed at enhancing the compound’s interactions with biological targets (Scheme 1). These acylated analogues were subsequently screened for their cytotoxicity against a panel of

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• the molecule. In this regard we performed the acylation of starting compound 8o using pivaloyl chloride. The process was carried out with 3-fold excess of the aforementioned reagent at reflux in MeCN for 3 h. As a result, product 13 bearing two acyl fragments at oxygen atoms of pyranone and pyrazole

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

• benefits of the photomechanochemical approach in the field of synthesis [77]. Specifically, they developed photomechanochemical conditions for the atom-transfer-radical addition (ATRA) of sulfonyl chlorides to alkenes, pinacol coupling of carbonyl compounds, decarboxylative acylation, and photocatalyzed [2

• acylation of electrophilic olefins (Scheme 11C). Compared to solution-phase photocatalysis, photomechanochemical conditions allowed to reduce the reaction time from 24 h to 3 h while maintaining comparable yields. Finally, the authors proved that photomechanochemistry contributes to the initial rate

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• agree with our previous results on tandem acylation/Diels–Alder reactions [31][32][33] and lead us to conclude that the final Diels–Alder reaction products are formed as the exo-adducts. Moreover, since we do not observe other stereoisomers we speculate that the Ugi and Diels–Alder reactions occur under

• beneficial aromatic product. Since we previously studied the reaction of 3-(thien-2-yl)allylamines with maleic anhydride [30], followed by a domino sequence involving successive acylation/[4 + 2] cycloaddition steps, that leads to the formation of the thieno[2,3-f]isoindole core, it was interesting to

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• [28]. In 2017, the Aϊssa group described a procedure to better synthesize such α-alkyl-substituted carbonyl sulfoxonium ylides [29]. This protocol involved the alkylation of a dialkyl thioether, counterion exchange, oxidation, and eventual acylation (Scheme 1a). More recently, the Burtoloso group

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• acylation of the 36 hydroxy groups on the CDs of [3]rotaxane proceeded effectively under the standard reaction conditions to yield perfectly acylated species (Figure 10B). Interestingly, the acylation of [3]rotaxane 7 at 60 °C did not proceed completely even after two weeks, although it did within 2.5 h at

• 80 °C. Additionally, that for a single native α-CD molecule proceeded completely at 60 °C within 2.5 h. Thus, the reaction temperature was confirmed as the key to completing the acylation reaction, probably because of the huge steric hindrance of the densely packed hydroxy groups on the [3]rotaxane

• bonding, resulting in the non-covered axle-end groups (Figure 11B, top). Meanwhile, the acylation of the hydroxy groups on the CDs expanded the cavity size along the axle, and the disappearance of the hydrogen bonding between the two CD units placed the CDs on the axle ends, causing the partial coverage