Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• -diiodonaphthalene (12) and thiophene-3-ylboronic acid and ester derivatives 17 under the optimized conditions reported in our previous work (Table 1) [43]. Gratifyingly, the reaction worked smoothly with the use of thiophene-3-ylboronic acid (17a) to give acenaphtho[1,2-b]thiophene (15a) in 76% yield when Pd(dppf

• ] or catechol [47] boronic esters as the final products. Therefore, it is important that they can be directly utilized with our methodology without further boronic ester interconversions. To this end, we first tested the reaction of thiophene-3-ylboronic acid pinacol ester (17b), and we were pleased to

• see that the desired product 15a was isolated with a similar reaction yield (78%, Table 1, entry 2). Thiophene-3-ylboronic acid catechol ester (17c) was also found to be a competent reaction partner affording the final product 15a successfully, albeit in a slightly lower yield (69%, Table 1, entry 3

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• : 4a (2 equiv), NaH (2.4 equiv), 2a, TEMPO (10 mol %), degassed DMF (0.055 M). NO – not observed. Mechanism proposed for sulfonamide 5, β-sulfinyl ester 4, disulfide 7, and sulfide 3 formations. The ionic steps are illustrated in green, whereas the radical steps appear in purple [35]. Optimization of

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

• yield of 4. Besides, the introduction of a boronic pinacol ester group, useful for subsequent post-functionalization, compound 7 was achieved in a relatively lower yield of 36%. Interestingly, the reaction also worked adequately for primary alkyl bromides with electron-withdrawing groups as demonstrated

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• chromene (12) were tolerated. Benzylic azides were accommodated including those bearing nitro (2), iodo (3), and boronic ester groups (5, 21). Strained rings were effective including cubane (18) and bicyclopentane (20). While 18 and 20 were isolated in lower yield, no evidence of ring opening was observed

• displaying an arylboronic acid and MIDA ester (22 and 23) gave no reaction, side reactions were observed with a dialkynyl germane (24), and the product derived from azide 25 was unstable to purification. To further demonstrate the compatibility and utility of germanyl alkynes in CuAAC reactions, we applied

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• a 4 mmol scale gave dimethyl ester 11a in 99% yield. Unexpectedly, the reaction of branched alcohols with diacyl chloride 2a failed. For example, the reaction with benzyl alcohol resulted in the formation of an overly complex mixture of products. Adding bases to trap HCl did not improve the

• situation. Dibenzyl ester 11c was prepared using traditional activation of carboxylic acid 6a, although the yield was only 23%. A higher yield of the branched ester 11d (86%, as a mixture of diastereomers) was obtained by carbene insertion, generated by blue LED irradiation of methyl 2-diazo-2-phenylacetate

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

• reported the α-alkylation of carbonyl sulfoxonium ylides via a Michael addition approach that occurred without any competition from cyclopropanation [30]. While this reaction represented the first direct alkylation of sulfoxonium ylides, it was nonetheless limited to the more reactive ester ylide variants

• studies using methyl ester sulfoxonium ylide 1a and 2,2,2-trifuoroethyl(mesityl)iodonium triflate salt (2a), as model substrates (see also Table S1 in Supporting Information File 1). Combining these at room temperature in acetonitrile produced 3a in 8% 1H NMR yield (Table 1, entry 1). Repeating the

• scope and limitations of this novel transformation (Scheme 2). Initially, we investigated the effects of introducing various substituents around the ester group of the carbonyl sulfoxonium ylide. We discovered that the reaction worked very well for various alkyl ester derived substrates (3b–g). For

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• or ester substituent. Firstly, the group of Haupt reported the synthesis of ethyl esters of tetrahydromethylpyridazine in 20% yield in a mixture of methanol and water by the reaction of methylhydrazine with acetylene dicarboxylic esters through the formation of enhydrazine (Scheme 1a), [23]. Later

• the ester function, as previously reported [32][33][34][35]. The corresponding adducts 5a–f were isolated with good yields from 66 to 88%. In the case of hydrazides 5e and 5f, the mixture of diastereomers (1:1 ratio) could not be separated at this stage. Although no stereoselectivity is observed, it

• chromatography. With dipeptides 7e and 7f stereoisomerically pure, we next focused our attention on the preparation of novel peptidic structures to perform some conformational analyses. Starting from the methyl ester 7, each diastereomer was engaged in a classical sequence of saponification in the presence of

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

• leads to the formation of the target product 139. Later, iron-catalyzed three-component reactions of α,β-unsaturated carbonyl compounds 140, aldehydes 141, and TBHP leading to α-ester-β-keto peroxides 142 have been developed (Scheme 45b) [106][107][108]. Radical coupling of arylaldehydes 144 with α,β

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• –CH2–(CF2)n–COOCH3 (n = 2,4,6, Tf = triflate) were synthesized. The triflates were reacted with 2-hydroxy-3,4,5-trimethoxybenzaldehyde via Williamson ether syntheses. The resulting electron-rich compounds were used as aldehydes in the Rothemund reaction with pyrrole to form ester-substituted porphyrins

• Williamson ether synthesis to yield 22 (78%), 23 (44%), and 24 (44%). Compounds 22, 23, and 24 were used as aldehyde components in the Rothemund-type synthesis of metal-free porphyrins 26 (9%), 27 (18%), and 28 (21%) (see Scheme 3). Metalation was achieved with nickel acetylacetonate to obtain the ester

• ester-functionalized aldehydes 22, 23, and 24. Conditions: a) NIS, TFA, Na2CO3, MeCN, reflux, 18 h; b) Cu2O·H2O, 2-pyridinaldoxime, TBAB, CsOH, H2O, N2, rt, 18 h; c) Cs2CO3, DMAc, N2, rt, 3 h. Porphyrin synthesis. a) Rothemund porphyrin synthesis of metal-free porphyrins 26, 27, and 28; b) metalation 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

• benzyl ester generated rather than the corresponding methyl esters. The reaction was also performed with a 6-membered cyclic diaryliodonium salt, which proceeded successfully and produced the respective iodo-containing arylated product in 59% yield with 76% ee after 24 h. Using the same reaction

• conditions, the arylation of tyrosine methyl ester was also performed. The resulting compound was arylated at both O- and N-positions. The investigations were continued with the unsymmetric anisyl salts, and the results showed high chemoselectivity for N-arylation. Iodonium salts containing the anisyl

• assessed as inhibitors of galectin-9 and were found to exhibit selectivity and potency against galectin-9. In 2021, Chen and colleagues developed a method to synthesize naproxen-containing diaryliodonium salts 67 using naproxen methyl ester 65 and ArI(OH)OTs 66, activated by trimethylsilyl

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• being explained by a tedious purification. Interestingly, the methodology was successfully applied to the functionalization of aliphatic hydrazones 1s and 1t and even the hydrazone derived from citronellal 1u. The method was functional group-tolerant to various functional groups (nitro, CN, ester

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• ). Dehydrogenation of the latter with DDQ afforded the anomerically pure indol-N-glycoside β-26a which upon benzylation and methylation gave products β-27a and β-27b, respectively. Iodination gave products β-28a and β-28b, however, due to the basic reaction conditions (I2, NaOH, DMF), ether rather than ester

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• the starting material porphyrin 13 being left unreacted. On switching the substrate from boronic acid to the boronic acid ester and opting for the weaker base Cs2CO3 instead of K3PO4, a significant difference in reactivity was observed with a 72% yield accomplished in the synthesis of porphyrin 29

• (Table 1, entry 9), bearing a methoxycarbonyl electron-withdrawing group utilizing boronic acid pinacol ester 18b. Following on from these results porphyrin 30 was synthesized in an 8% yield, when switching to weaker base Cs2CO3 using pinacol ester 16b (Table 1, entry 6). Switching the base to a weaker

• observed (Table 3, entries 9 and 10). 4-Pyridylboronic acid pinacol ester (25) was also attempted; however, no product was formed. Vinylboronic acid ester 22, was also explored as a substrate, with multiple porphyrin products being observed by TLC and by 1H NMR. Desymmetrization of the porphyrin was also

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

• ester was also a suitable substrate for the reaction (Scheme 20, 20p). In addition, the presence of substituents such as hydroxy or chlorine groups on the anthrones had no impact on the reaction (Scheme 20, 20q–t). Chiral coumarins, renowned for their bioactive properties, form the cornerstone of

• vinyl allenylidene species. A series of differently substituted spiro-cyclic products can be obtained with high yields, regio- and stereoselectivities (Scheme 32, 30a–x). Preliminary mechanistic studies indicated that the reaction first undergoes a substitution at the α-position of yne-allylic ester

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• (Table 3, entries 1–3). Introduction of 3,4-methylenedioxyphenyl (4e) or p-fluorophenyl groups (4f) to 1a proceeded in high yields (Table 3, entries 4 and 5). Boronic acids with carbonyl groups such as acetyl, ester or formyl moieties in para position (4g–i) underwent the cross-coupling in 76, 96 or 77

• –Miyaura cross-coupling. The reaction of 1b or 1c, which had a m-methoxy or p-nitro group on the benzene ring, with 4a proceeded smoothly to furnish 2p or 2q in good yieds (Table 3, entries 15 and 16). A phenyl group could be introduced into 1d possessing an ester moiety in moderate yield, whereas the

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