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

• acetate gave monoacetate 111 in 98% yield and >98% ee. Subsequently, monoacetate 111 was converted into compound 112 with a 1,3-dioxan-2-one moiety in three steps, which underwent Pd-catalyzed decarboxylation/carbonylation to form the lactone 113. The N-methylimidazole ring was installed through a three

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• is the retrosynthetic analysis for the key intermediate 1, which can reach the final compound VI via chlorination and demethylation [19]. Target molecule 1 can be accessed by decarboxylation reaction from compound 13, prepared by an intramolecular Heck reaction between the β-ketoester and the vinyl

• not known). A hydrogenation reaction to reduce the C=C bond in 11 was then successfully applied, delivering product 12 in 80% yield (5 mol % RhCl(PPh3)3 catalyst and 1 atm hydrogen atmosphere were used). Next, we tested whether Krapcho decarboxylation reaction can convert 12 into 1 in one step

• , photocatalytic decarboxylation [34] delivered the desired product 1 in 74% yield, realizing a formal synthesis of the selective estrogen receptor modulator VI. Conclusion In conclusion, we achieved a formal synthesis of SERM molecule VI through a 11-step process to its precursor, molecule 1. Two key reactions

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

• decarboxylation was induced by a photochemical oxidation using an iridium catalyst, and the resulting benzylic radicals were coupled with activated alkenes through a Giese addition which was irreversible due to the strained nature of the starting radicals. As a result, radical dimerization was minimal and the 3,3

• groups including esters, ketones, sulphones and heteroaryls. The mechanistic proposal, supported by DFT calculations, starts with an oxidative decarboxylation to give an aminooxetanyl radical 157. This species is in turn coupled with the aryl halide by the active Ni(0) catalyst (generated in situ by

• 175 in a divergent synthesis of 3,3-disubstituted oxetane amino esters 176 based on a facile, strain-release-driven Giese addition of nitrogen- or oxygen-stabilised radicals (Scheme 44) [96]. The radicals were generated through a photochemical oxidative decarboxylation of amino- or alkoxycarboxylic

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

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

• 0.4% amount of cat. 1 provided adduct 30 in 72% yield with 92% enantioselectivity, and the reaction could be scaled up to decagrams. Subsequent decarboxylation and recrystallization of the resulting ketone 31 yielded an enantiopure product (99% ee), which serves as a versatile intermediate for the

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

• mechanism for the formation of the key intermediate 69 is outlined in Scheme 19: first, substrate 67, under the action of a copper catalyst and diisopropylethylamine, undergoes a decarboxylation process to generate the allylidenecopper intermediate Int-63 and its resonance form Int-64. Subsequently, these

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

• under constant current conditions in aqueous acetonitrile and provides access to N-sulfonyl, N-benzoyl, and N-Boc-protected 2-aminoproline derivatives. Keywords: anodic oxidation; decarboxylation; electrosynthesis; Hofer–Moest reaction; non-proteinogenic amino acids; Introduction Non-proteinogenic

• tetrahydropyran-containing amino acid derivatives via anodic decarboxylation of N-acetylamino malonic acid monoesters to generate a stabilized carbocation (Hofer–Moest conditions), which were then reacted with a tethered oxygen nucleophile [4]. In this follow-up study, we demonstrate that N-protected amines are

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

• (Scheme 30). As glyoxylates are C2 structures, their use as C1 building blocks in MCRs instead of formaldehyde, requires an extra path, usually a decarboxylation process, after the condensation reaction. However, by appropriately choosing the glyoxylate derivatives (for example, ethyl glyoxylate), post

• regioisomer with very good yields. For the immobilized glyoxylic acid, the best conditions required the use of the methanol-compatible resin, MP-carbonate. After coupling of the three components, decarboxylation at 50 °C released the product, while, when working with 'free' glyoxylic acid, decarboxylation

• derivatives 43 with very good yields and for a wide range of amines and tosyl methyl isocyanides, after a decarboxylation/elimination sequence of the putative intermediate 45. This procedure was the basis for the work by Dow et al. on the synthesis of a new series of CB1 receptor antagonists (cannabinoid-1

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• olefine (5R,9R)-12, which could be obtained through Li2CuCl4-catalyzed coupling of chiral tosylate (S)-10 with a Grignard reagent derived from (R)-1-bromo-2-methylbutane ((R)-11). The key chiral building block (S)-10 was envisaged to be prepared through a sequence of hydrolyzation, decarboxylation, borane

• ]. Similarly, chiral tosylate (R)-10 could be prepared from (S)-2-methyloxirane ((S)-2) through the ring-opening reaction, tosylation, stereospecific inversion, hydrolysis, decarboxylation, reduction, and second tosylation (Scheme 3). With two the chiral building blocks (R)-10 and (S)-10 in hand, we next

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

• the substrate, an activated ester 25, subsequently generating carbon-centered radicals without the need for sacrificial electron donors via a decarboxylation process. In reacting with electron-deficient alkenes or alkynes 26, these radicals further yield tetralin and dialin moieties 27, respectively

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

• amidation process of dioxazolones. Dioxazolone 1 binds to the chiral copper complex 3, generating the adduct INT-1. Decarboxylation then occurs, forming the copper nitrenoid intermediate INT-2, subsequently undergoing hydrogen atom transfer in a regioselective manner to afford INT-3. The related acyl

• , a plausible reaction pathway is described in Figure 6. Decarboxylation of dioxazolone in INT-22 forms the copper nitrene intermediate INT-23. The thiol then attacks the electrophilic nitrogen center of INT-23, which further leads to the formation of intermediate INT-24. Finally, the desired product

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• ) results in (methoxycarbonyl(iodo)methyl)triphenylphosphonium salt 5 (observed by MS). Deiodination or decarboxylation from this intermediate afford 6 and 7, respectively. After heating to T2, (methyl)triphenylphosphonium salt 8 is observed, which may be formed from 6 and 7 by decarboxylation and loss of

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

• decarboxylation of α,α-difluoro-β-keto acid esters 11 with the help of aryl(TMP)iodonium tosylates 12 in toluene at 100 °C to yield α,α-difluoroketones 13 in excellent yield (Scheme 4). The reaction proceeds via ligand exchange between the fluorinated carboxylate and the tosylate anion of the hypervalent iodine

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• decarboxylation accompanied by aromatization of the oxazole ring occurred during this process. Thus, protonation occurs, leading to oxazole 5 when the reaction mixture is warmed in the presence of large amounts of proton sources such as acetic acid or deuterium oxide. Although Nagao et al. proposed another

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• versatile method using decarbonylation of benzofuranone followed by oxidation, that produces only CO2 as a non-toxic side product, is considered less hazardous. Although decarboxylation of aldehydes, carboxylic acids, and ketones are well known, albeit using metal catalysts, decarboxylation methods for

• lactones are limited. Both photochemical decarboxylation methods reported for α,γ-butyrolactone [16] and γ-butyrolactones [17] yielded the products in very poor to moderate yields (Figure 2a and 2b). Recently, a transition-metal-free decarboxylation of α,β-unsaturated aromatic lactones was reported for the

• synthesis of E-o-hydroxystilbenes, albeit via a cascade hydrolyzation–decarboxylation reaction at a very high temperature (Figure 2c) [18]. However, a metal-free decarbonylation–oxidation method for benzofuranones is still unprecedented. The earlier report [2] on the Ni-catalyzed decarbonylation–oxidation

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

• anodic oxidation cleaves the diazene, resulting in the formation of an acyl radical and the release of molecular nitrogen. The subsequent step involves the decarboxylation of the acyl radical to produce an alkyl radical. This method was successfully applied to the late-stage functionalization of

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• , respectively) [243], showed inhibitory potential against various protein kinases with IC50 values of 1.5–9.7 µg/mL [147], and displayed significant scavenging activities against nitrite [243]. Biosynthetic decarboxylation of desmethylaltenusin affords biaryl 49, which was isolated from Penicillium sp. [244

• ] and from Talaromyces sp. [243]. It showed significant α-glucosidase inhibition with an IC50 value of 2.2 μM [244] and was a potent scavenger of DPPH and of nitrite [243]. Decarboxyaltenusin (50) was reported in 1974 to be obtained by chemical decarboxylation of altenusin (47) and by reduction of

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• produced hydrazones 29. After deprotonation, the authors proposed that the carboxylate anion underwent SET anodic oxidation/decarboxylation/radical cyclization sequence to form radical intermediates 34. Subsequent second anodic oxidation and deprotonation yielded the desired heteroaromatic 5-membered rings

• 38. As such, the iodide electrolyte served as an electromediator to both promote the decarboxylation process and protect the aniline product from overoxidation. Importantly, a control experiment without electricity but in the presence of molecular iodine instead proceeded smoothly, thereby confirming

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

• protocols [70][71]. In these experiments, compounds 6b and 6i proved to be unstable under on-DNA conditions as they failed to form esters 8b and 8i. Closely related structures, such as α-aminobenzothiazol-2-ylacetic acid is known to undergo decarboxylation at room temperature [72]. Compound 8t underwent

• decarboxylation during the hydrolysis step. Compounds 6j, 6l and 6r passed validation in moderate to good yields (Scheme 8). Conclusion In conclusion, by taking advantage of the recent advances in the Negishi cross-coupling reaction we obtained a broad range of heteroarylacetates starting from heteroaromatic

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• -methoxyethylamine. Attempts to obtain directly 2-oxoazetidine carboxylic acid (or its decarboxylation product) or its trifluoroethyl ester by running the synthesis with water or trifluoroethanol were also unsuccessful. Acylation of the π-excessive double bonds of N-alkylindole and dihydropyran by the in situ

• high yields of the target compounds. When stored individually or in solution at room temperature, the acids 4 gradually decompose and undergo decarboxylation and other accompanying processes. The example of acid 4a demonstrates the possibility of easy amidation to form new β-lactam derivatives 3s and

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• -heteroarylethylamine chemical space is constituted by the biogenic amine histamine (43). In a similar fashion as dopamine and epinephrine produced from ʟ-phenylalanine along the catecholamine pathway, histamine is generated from the amino acid ʟ-histidine (42) via enzymatic decarboxylation promoted by ʟ-histidine

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

• decarboxylation of the carboxylic residue when heated at reflux of methanol. After the regioselective cycloadditions, spiro compounds 49a,b were obtained in yields ranging from 75% to 91% (Scheme 15). Related derivatives have similarly been achieved in good to excellent yields [32][33]. Recently, López et al

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• TylGI loads a methylmalonyl-CoA onto the acyl carrier protein (ACP) in module 1. The ketosynthase-like decarboxylase (KSQ) domain catalyzes the decarboxylation of the loaded methylmalonyl moiety, and subsequent modules 2 and 3 extend the carbon chain using two molecules of malonyl-CoA. The β