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

• etherification and aldol reactions [197]. Cyclopentanone (CPN) Cyclopentanone (CPN) can be prepared by catalytic hydrogenation and Piancatelli rearrangement of furfural (Scheme 65). This is a biobased alternative to the fossil-based process relying on the intramolecular decarboxylative cyclization of adipic acid

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• were developed. A straightforward transformation was designed involving a cross-metathesis of the C13–C14 double bond and a palladium-catalyzed decarboxylative allylation [32] as the key steps. With 14 in hand, we investigated the feasibility of cross-metathesis of the C13–C14 double bond. Initially

• of 21 with allyl alcohol and triphenylphosphine afforded transesterification product 22 in 21% yield [33], accompanied by unidentified decarboxylation by-products. A variety of standard conditions failed to promote the palladium-catalyzed decarboxylative allylation of allylic β-ketocarboxylate

• was treated with p-toluenesulfonic acid (p-TSA) in EtOH at room temperature to afford ketal 24 in 83% yield as a single diastereomer. Subsequently, palladium-catalyzed decarboxylative allylation delivered compound 25 in 89% yield. The efficiency of our first-generation strategy for asymmetric

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• , decarboxylative functionalizations, and Chan–Lam coupling reactions. In doing so, the authors point out the combination of transition-metal catalysis and electrochemistry as an efficient, sustainable method for the oftentimes challenging formation of C–C and C–heteroatom bonds in complex molecules. Another Review

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• heteroarenes. This practical synthesis of 3-aryloxetan-3-carboxylic acids potentially opened the door to installation of a wide range of substituents into the 3-position through a decarboxylative radical coupling, which was eventually exploited by Duarte and Bull et al. in 2023 (Scheme 38) [89]. The

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

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

• interesting transformation of cinnamic acid to its derivatives can be achieved through decarboxylative cross-coupling. Recently, Wang and co-workers (2024) reported the Ag-catalyzed decarboxylative cross-coupling of cinnamic acids with isocyanide to give the corresponding amides 258–260. The reaction involves

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

• team designed a new class of acetylene carbonate reagents and successfully applied them to copper-catalyzed decarboxylative amination/hydroamination sequences (Scheme 18) [48]. By controlling acidic and basic reaction conditions, the authors achieved the controllable synthesis of two types of

• decarboxylative amination/hydroamination sequence [48]. Proposed mechanism of copper-catalyzed decarboxylative amination/hydroamination sequence [48]. Enantioselective chemodivergent three-component radical tandem reactions [49]. Substrate-controlled synthesis of indoles and 3H-indoles [52]. Controlled mono- and

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• 10.3762/bjoc.21.50 Abstract The electrochemical synthesis of 2-aminoprolines based on anodic decarboxylation–intramolecular amidation of readily available N-acetylamino malonic acid monoesters is reported. The decarboxylative amidation under Hofer–Moest reaction conditions proceeds in an undivided cell

• in three steps (62% overall yield) from commercially available diethyl acetamidomalonate by an alkylation/hydrolysis/Boc-cleavage sequence (Scheme 1). The development of decarboxylative amidation commenced by examining the published conditions for anodic decarboxylation/etherification [4

• feature at Ep = 1.78 V vs Ag/Ag+ (100 mV/s scan rate; see Figure 3A), and the electrolysis of pyrrolidine 6a under the optimized anodic decarboxylative cyclization conditions (entry 8, Table 1) afforded cyclic hemiaminal 12a (33% NMR yield), whose structure was proved by NMR experiments (Figure 3B). The

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

• final products, however, it can be released after a decarboxylative or reductive reaction (β-position), allowing the use of ethyl glyoxylate as a C1 building block. This strategy was explored by Miranda et al., who first obtained a series of γ-lactams 56 and isoindolinones 57 using ammonium persulfate

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

• enables solvent-free conditions for this transformation (Scheme 11B). Here, the aggregation state of the substrate and the reductant proved to be crucial to establish a fully operative protocol. The third reaction tested under mechanophotocatalytic conditions was the well-established decarboxylative

• reactions: A) atom-transfer-radical addition, B) pinacol coupling, C) decarboxylative alkylation, D) [2 + 2] cycloaddition. The photo in Scheme 11 was reproduced from [77] (© 2024 F. Millward et al., published by Wiley-VCH GmbH, distributed under the terms of the Creative Commons Attribution 4.0

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

• depicted in Figure 2. The reaction is initiated by formation of the five-membered copper-containing intermediate INT-5 through coordination of Cu(OAc)2 with the N-iminoquinolinium ylide species 5. This process is followed by decarboxylative N–O bond insertion into 4, yielding the N-acyl copper(III

• ) chloride reacts with boronic acids, forming the copper aryl complex INT-16, which then undergoes decarboxylative N–O bond insertion to generate the copper nitrenoid intermediate INT-17. Thereafter, nitrene insertion into the copper–carbon bond occurs, forming a new C(sp2)–N bond (INT-18). Finally, the

• and silane, undergoes the enantio-determining hydrocupration of the vinylarene, affording INT-25 [25]. Next, oxidative insertion of INT-25 into the N–O bond of the dioxazolone, forms INT-26, followed by decarboxylative reductive elimination to generate INT-27. Further incorporation of silane delivers

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

• catalysis to organic synthesis, focusing on recent developments in Cu-catalyzed electrochemical reaction categorized into four types: 1) C–H functionalization, 2) olefin addition, 3) decarboxylative functionalization, and 4) coupling reactions (Figure 3). This review aims to provide insight into the

• desired annulation products. Moreover, the same products were generated using alkynyl carboxylic acids instead of terminal alkynes via decarboxylative C–H alkynylation and annulation. Cyclic voltammetry (CV) studies exhibited an oxidative current at 0.95 V vs SCE in the presence of the Cu(II) salt, base

• Cu(I)CN catalyst 108. The Cu(II)CN catalyst 109 is regenerated via anodic oxidation to complete its catalytic cycle. Decarboxylative functionalization Carboxylic acids are inexpensive, readily available, structurally diverse from both natural and synthetic sources, and easy to handle. Recently

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

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

• were explored, using a total volume of 4.5 mL reaction mixture, and the screening results can be readily translated to continuous flow synthesis. The application of segmented flow or microslug reactors was demonstrated in the decarboxylative arylation cross-coupling reaction promoted by catalysts and

• -flow pattern using a Y-shaped mixer, followed by the suspension of the catalyst via a T-mixer. This technology was utilized to develop selective and efficient decarboxylative fluorination reactions. Recently, a slug flow platform was developed (Figure 3a) by injecting segments of gas as a separating

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• transformations of biomolecules, such as thiol–yne reaction and decarboxylative alkynylation. The thiol–yne reaction of cyclohexanethiol (90) with phenylacetylene (89) in the presence of 1 mol % of H2TPP (18) under red LED irradiation provided the desired product 91 in up to 85% yield while the decarboxylative

• in red light-induced C–X-bond formation on biologically relevant molecules 95–97, based on a thiol–yne reaction and decarboxylative alkynylation protocol (Figure 17d). Last year, Moyano and colleagues reported on amino-functionalized porphyrins as bifunctional organophotocatalysts, effectively

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• in situ-generated Cu(I) complexes was developed (Scheme 23) [43]. 2-Phenylbutane (64) was converted into peroxide 65 in a 70% yield with 4% ee. A visible light-induced direct decarboxylative peroxidation of carboxylic acids 66 with the formation of peroxides 67 under metal-free conditions using Mes

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• salt, subsequently leading to decarboxylative C–C coupling. Notably, this method achieves the incorporation of two fluorine atoms in the benzyl position without resorting to hazardous fluorination reagents, transition-metal catalysts, or organometallic compounds. The utility of this reaction is

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

• , 6a–w). Interestingly, both Cu(I) and Cu(II) can promote the reaction and the reaction is not sensitive to water (Scheme 7, 6g). The intramolecular decarboxylative yne-allylic substitution can also be achieved (Scheme 8, 6a–u). O-Nucleophiles and C-nucleophiles are all suitable reactants, yielding

• . Amine-participated asymmetric yne-allylic substitution. Asymmetric decarboxylative yne-allylic substitution. Asymmetric yne-allylic alkoxylation and alkylation. Proposed mechanism for Cu(I) system. Asymmetric yne-allylic dialkylamination. Proposed mechanism of yne-allylic dialkylamination. Asymmetric

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

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• fluorides have also been reviewed, such as through deoxyfluorination, C–X fluorination, or decarboxylative fluorination [22][31][32][33]. However, a comprehensive review that focusses specifically on benzylic C–H bonds is still currently missing in the literature. Therefore, we aim to cover reports that

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• .20.133 Abstract We report a practical and sustainable electrophotochemical metal-catalyzed protocol for decarboxylative cyanation of simple aliphatic carboxylic acids. This environmentally friendly method features easy availability of substrates, broad functional group compatibility, and directly

• ][18]. Owing to the prevalence of aliphatic carboxylic acids in biomass and natural products, decarboxylative cyanation represents one of the most straightforward and attractive approaches to accessing alkylnitriles [19][20]. As an elegant example, Barton demonstrated the application of redox-active

• esters, the so called "Barton esters", for decarboxylative cyanation of aliphatic acids with tosyl cyanide as the nitrile source under visible light irradiation at room temperature [21][22]. Although two synthetic steps are required, this is the first practical decarboxylative cyanation protocol because

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• ) [3][4]. The building blocks for PKS biosynthesis often include malonyl-CoA or methylmalonyl-CoA, which are loaded onto the ACP by the AT domain. Subsequently, the KS domain catalyzes the decarboxylative Claisen condensation between the ACP-tethered extender unit and the KS-tethered growing chain. The

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• esterification of alcohol (±)-5 gave redox active ester (±)-6, which was itself shown to be a suitable substrate for nickel-catalysed decarboxylative cross coupling reactions to aryl-substituted BCPs (±)-7. Oxidation of alcohol (±)-8 gave acid (±)-9 which yielded amine (±)-10 after a Curtius rearrangement

• decarboxylation then yields 1,2-cubane 88. This synthesis reduced the number of synthetic steps from eight, in the previously known patented synthesis from 2007 [54], to four. MacMillan and co-workers also developed a number of decarboxylative cross-coupling reactions to allow access to an even wider range of 1,2

• -cubanes (Scheme 9B) [51]. Partial deprotection of diester 88 led to acid 89 as a key intermediate and in situ activation of the acid as the hypervalent iodine complex enabled a photoredox decarboxylative amination to 1,2-cubane 90. Alternatively, conversion of the acid moiety of 89 to redox active esters

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• : the acyl transferases (AT) for loading of the starter or extender units, the acyl carrier proteins (ACP) for anchoring the growing polyketide chain, and the ketosynthases (KS) for merging of the next extender unit with the existing chain by a decarboxylative Claisen condensation [2][4]. Today a high

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• many applications as radical precursors. Mechanistically, NHPI esters undergo a reductive decarboxylative fragmentation to provide a substrate radical capable of engaging in diverse transformations. Their reduction via single-electron transfer (SET) can occur under thermal, photochemical, or

• of parameters with which to control reactivity. In this perspective, we provide an overview of the different mechanisms for radical reactions involving NHPI esters, with an emphasis on recent applications in radical additions, cyclizations and decarboxylative cross-coupling reactions. Within these

• reaction classes, we discuss the utility of the NHPI esters, with an eye towards their continued development in complexity-generating transformations. Keywords: decarboxylative couplings; mechanisms; NHPI-esters; radical reactions; Introduction The historical challenges of using radicals in synthetic