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

• -hydroxybenzophenones are conventionally prepared via Fries rearrangement of a phenyl ester [10]. Organocatalytic methods have also been reported for the synthesis of 2-hydroxybenzophenones [11]. In addition, several metal-mediated methods for their synthesis have been reported. For example, the Rh-catalyzed

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• , Figure S1), confirming the acid functional group in the natural compounds. In support of these data, GC/IR analysis of Dm (Supporting Information File 1, Figure S2) showed strong carbonyl bands at 1741 cm−1 accompanied by two intermediate bands at 1198 cm−1 and 1177 cm−1, characteristic of ester valence

• located at C-4 or C-5, a second one is located at C-6 or C-7, and a double bond at C-5. The positional ambiguities were resolved by the derivatization of a crude extract with pyridin-3-ylmethanol, yielding pyridylmethyl esters [8][25]. The spectrum of the pyridylmethyl ester derivative Dp confirmed that

•  3). Since A–F were obviously a homologous series of compounds, we synthesized compound D as its methyl ester Dm to compare the mass spectrum and I with those of the methyl esters of the natural acids. Methyl 4,6-dimethyldodec-5-enoate (6) was synthesized as a mixture of E/Z isomers (Scheme 1

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• 2 in BTF (0.4 mL) at 80 °C in air successfully afforded phenylboronic acid pinacol ester 3a in 68% yield (Table 1, entry 1). In the presence of NaOMe as a base, the reaction did not proceed (Table 1, entry 2). Increasing or decreasing the amount of diboron 2 did not improve the yield of 3a (Table 1

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

• . For example, Liu and colleagues demonstrated the electrochemical oxidation of benzylic C–H bonds to ketones using tert-butyl hydroperoxide as the radical initiator [14]. This method was applied to functionalize bioactive molecules, with celestolide, ibuprofen methyl ester, and papaverine being

• direct activation of C(sp3)–H bonds under mild conditions [17]. The pronounced electron-deficient W2C nanocatalysts greatly facilitate the direct deprotonation process, ensuring the longevity of the electrode by overcoming self-oxidation. The LSF of drug molecules such as ibuprofen methyl ester and

• methanol, equipped with a graphite anode and a platinum plate cathode, under a current of 10 mA at 60 °C for 3–20 hours. Several electrochemical LSF of pharmacologically active molecules were tested, including naproxen methyl ester, a derivative of aminoglutethimide, and paracetamol. The corresponding

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• benzoyl group on the nitrogen atom preventing equilibration to the thermodynamic piperidine product [21]. Basic workup hydrolyzes the trifluoroacetoxy ester in 14 to alcohol 7a. Consideration of the literature NMR data for the three possible isomeric products (i.e., pyrrolidine, piperidine, and

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• . If the in situ conversion of anti,syn-7a to anti,syn-7b follows the above ester alcohol exchange mechanism, employment of dibenzyl malonate should afford a single compound. This is actually the case and the expected dihydrofuran anti,syn-7c was obtained in 53% yield as a 98:2 diastereomer mixture

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• the phenyl ring [17]. To the best of our knowledge, this is the first report on electrochemical carboxylation of benzyl alcohols. Only benzyl alcohols having an electron-withdrawing group, such as cyano or ester in the ortho- or para-position of the phenyl ring, were efficiently carboxylated by

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• -diaminonaphthalene derivatives 42, which after hydrolysis and extraction into toluene, were reacted with indole, 3-methylindole, 3,4-dihydroisoquinoline, and benzoyl hydrazone ethyl glyoxylate ester to afford terminal (E)-trifluoromethyl homoallylic amines 44 with up to 3 adjacent stereocentres with high to

• . 3,3’-Diaryl-BINOL-catalysed asymmetric organocatalytic allylation of acylimines [24]. Aminophenol-catalysed reaction between N-phosphinoylimines and pinacol allylboronic ester. Imine scope [6]. aReaction time: 6 h. Asymmetric geranylation and prenylation of indoles catalysed by (R)- or (S)-3,3

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

• analogue, the DMP-tag, which in contrast to standardly used isotopic tags bearing the N-hydroxysuccinimide ester (NHS-ester) reacting with all primary amines of lysine side-chains, allows to selectively label the probe–protein conjugates (Figure 7A) [81][83]. The DMP-tag can be prepared in a six-steps

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• both conditions. This result could be ascribed to the lower affinity of the oxo-ester to form active nucleophiles in comparison to the more favorable enolization of thiomalonates. The stereochemical outcome of the thiomalonate’s addition could be rationalized by the assumption the iminium ion

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• H-iPr-nicardipine was higher (8 min) related to enhanced ester stability with an isopropyl group versus a methyl ester. Collectively these results point to high potential for translation in vivo where novel deuterated analogs exhibit longer t1/2 and by extension oral bioavailability. Conclusion In

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• , DBAs substituted with electron-withdrawing groups have been little studied [19], and their chemical stability and physical properties are not well understood. In this paper, a new DBA substituted with ester groups was synthesized, and the double azide addition was comprehensively investigated. Finally

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• situ-generated acetone imines in a (3 + 3) manner to afford meta-substituted anilines (Scheme 1C) [53][54]. Various EWGs (ester, carbamoyl, ketone, trifluoromethyl) have been successfully employed which motivated us to evaluate other possible EWGs. Results and Discussion Based on the fact, that many

• heterocycles are isoelectronic to an ester or a carbamoyl group, we were interested in testing various heterocycles as electron-withdrawing groups for activation of the carbonyl group in 1,3-diketones. In order to compare the electron-withdrawing ability of heterocycles and previously studied EWGs, we tried to

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• ester of desmethylaltenusin, was isolated from Alternaria alternata; it showed neuroprotective effects against oxidative stress-mediated damages in PC12 cells [213]. Two further biaryl derivatives are most likely derived from alternariol and their biosynthesis similarly seems to include a reductive bond

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• -cyanoalkylation of benzoyl or ester group-substituted fluoroalkyl aryl sulfoxides with various alkyl nitriles in two steps [48]. The addition of a base in the second step easily enabled the [3,3]-rearrangement, allowing for the addition of two functional groups – the cyano group and difluoromethylthio group – to

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

• dihydropyridines, specifically 3,5-acyl-1,4 dihydropyridines 77, are well suited for undergoing ring opening-ring closing cyclocondensation with hydrazine in a pseudo-multicomponent reaction to give bis(pyrazolyl)methanes 78 (Scheme 28) [106]. Interestingly, the use of ester derivatives leads to the formation of

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• not have a significant effect on the yield or formation of respective products (Table 1, entry 12). Based on the optimization studies, a combination of KOH in toluene and TBAB (Table 1, entry 2) as phase-transfer catalyst was chosen as the best conditions. Although KOH could saponify the ester group

• predominates over saponification under our mild conditions (room temperature). Overall, the reaction proceeds smoothly without any unwanted side reactions such as saponification of the ester groups. Having optimized the reaction conditions, we proceeded to examine the substrate scope of the developed

• to the increase in electron density at the carbon β to the ester group thus inhibiting the Michael addition of curcumin (Table 2, entry 4). Arylidenemalonate 2e, bearing a weakly electron-donating substituent, reacted with 1a to afford the double Michael adduct 3e in moderate yield (46%), and the

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• OPPh3 contributing to the increased error and standard deviation. Compound 6 was completely consumed and not detected (see Supporting Information File 1). Mechanistic considerations Alam and Keeting proposed a deprotonated intermediate that utilized the indazole N2 and C=O from an ester substituent at C

• system (Figure 10). Under conditions A, deprotonation and cesium coordination were heavily favored by 11.1 kcal/mol (18(N-H)). Transition states 18-N2-Cs and 18-N1-Cs were found leading to N1- and N2-products, respectively. NCIs between the cesium cation with the ester and sulfonate oxygens, and

• indazole and the deprotonated indazole was only −0.2 kcal/mol (Figure 11). Again, no preorganized intermediates were found. The NCIs were consistent with the parent system. The hydrogen bond between the H on the electrophilic methyl group and an ester oxygen was found in the transition state leading to the

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

• proceeded smoothly yielding 4j in quantitative yield. However, obtaining compound 4r presented some challenges due to the resistance of ester 2r towards conventional oxidation methods (see Table S5 in Supporting Information File 1). Consequently, a multi-step process involving ester hydrolysis and

• methods were tested and after a brief optimization process, zinc dust and HCl in a mixture of EtOH/dioxane proved to be the best conditions in order to maximize the yield and limit the amino ester instability issues (see Table S6 in Supporting Information File 1). By slightly adjusting the reaction time

• first attached to carboxylic acid functionalized DNA headpiece 7a (first reverse amidation). Next, the ester was hydrolyzed to obtain acid 9, and finally, a second reverse amidation with aniline afforded 10. Both the reverse amidation and the ester hydrolysis were performed following literature

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

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

• ester) was positioned in the aldehyde precursors 86 (Scheme 28). Various 2-aminothiazoles 87 and tert-butyl isocyanide (5) were reacted with 86 in the presence of Yb(OTf)3, affording 88. Addition of a new aliquot of Yb(OTf)3 (30 mol %) allowed the new ring formation through a 7-exo-trig intramolecular

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• -valerolactones 7 and 8, which are functionalized with sulfur and nitrogen, in high yields. Additionally, optically active δ-valerolactone 3a was converted to optically active epoxy-ester 9 upon treatment with potassium carbonate in methanol. Notably, the transformed products were obtained without any loss of

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

• diazo precursor. To achieve this, cholesterol was first esterificated using 2-(4-methoxyphenyl)acetic acid and DCC. The resulting arylacetic ester 12 was then reacted with 4-acetamidobenzenesulfonyl azide (p-ABSA) and DBU in anhydrous acetonitrile to yield the diazo compound 13 in 22% yield. The carbene

• final CO insertion to release the ester. After an acid hydrolysis which produced 36, a basic treatment induced the condensation reaction to yield the heterocycle 37 in 99% yield. This reaction sequence was also applied to the acetates of ethisterone and ethynylestradiol, resulting in similar yields in

• ester under basic conditions was carried out, followed by the transformation of the carboxyl group to the amides 165 and 166 by treatment with thionyl chloride and the corresponding amine. Tetraoxanes were obtained from ketones 163, 165, and 166 by a peroxyacylation reaction using an acidic hydrogen

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

• Suzuki–Miyaura coupling with boronic ester 53 and O-acetylation furnished 54. The dienophile component, morachalcone A (44), was synthesized from phenol 55 in four steps including O-prenylation and subsequent Claisen rearrangement, aldol condensation with 56, and deprotection. The key chemo-enzymatic

• this problem, the research group designed synthetic substrate analogs (96, 101) that mimic the biosynthetic intermediate 88 (Scheme 10A). By replacing an amide linkage in 88 with an ester linkage, the fatty acid side chain could be removed under mild conditions after enzymatic construction of the

• pentacyclic secondary amine 97 bearing the ester linker in the C1 side chain in one pot. After removal of SfmC by precipitation and centrifugation, the reaction mixture containing secondary amine 97 was subjected to the reductive amination using 2-picoline borane as a hydride source, yielding tertiary amine

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• ]. Further O-MTs can be classified based on a common acceptor group of modification, namely C-terminal carboxy-MTs and peptide/protein ʟ-aspartyl O-MTs (PAMTs). C-terminal carboxymethyltransferases Carboxy-MTs catalyse the formation of a methyl ester by methylating the oxygen atom within the hydroxy group of

• enzyme engineering and rational design [73][74]. Lentzea kentuckyensis sp. produces lassomycin (Figure 4), a lasso peptide, with a methyl ester at the C-terminus. The las cluster encodes LasF, which is predicted to function as an O-MT. Since no other putative MT is encoded in the las cluster, LasF is

• proposed to methylate lassomycin [77]. PAMTs – peptide/protein ʟ-aspartyl O-methyltransferases PAMTs share a conserved C-terminal domain, substantial sequence homology, and a common enzymatic activity. They catalyse the conversion between aspartate and isoaspartate with aspartyl-O-methyl ester and