Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ether (60–90 °C)/ethyl acetate 60:1, v/v) to give 2a (47.3 mg, 91%). Typical procedure for the preparation of β-keto amides 3 (3a as an example) A mixture of (E)-3-(ethylthio)-1-phenyl-3-(phenylamino)prop-2-en-1-one (1a, 70.8 mg, 0.25 mmol), NaOH (30 mg, 0.75 mmol) and PEG-400 (0.236 mL, 0.75 mmol) in

• organic solution was dried with anhydrous Na2SO4, and the crude product was purified by column chromatography on 30–400 mesh silica gel (petroleum ether (60–90 °C)/ethyl acetate 20:1, v/v) to give 3a (53.8 mg, 90%). Synthesis of α-keto thioesters and β-keto amides. Synthesis of β-keto thioesters 2

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• funnel with the aid of 10 mL of deionized (DI) water followed by 20 mL of diethyl ether. The organic layer was separated, dried with anhydrous magnesium sulfate, filtered, and the solvent removed in vacuo to afford the crude product, which was first analyzed by 1H NMR spectroscopy and then purified using

• potential conditions of 2 V with no reference electrode until 2.5 F/mol was passed. Following completion of each reaction, the mixture was transferred to a separatory funnel with the aid of 10 mL of DI water followed by 20 mL of diethyl ether. The organic layer was separated, dried with anhydrous magnesium

• funnel with the aid of 10 mL of DI water followed by 20 mL of diethyl ether. The organic layer was separated, dried with anhydrous magnesium sulfate, filtered, and the solvent removed in vacuo to afford the crude product, which was first analyzed by 1H NMR spectroscopy and then purified using flash

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• 9-O-methyl ether, altenusin, dehydroaltenusin, altertenuol, and altenuene) were frequently found and isolated as fungal contaminants in food and feed and have been investigated in significant detail, further metabolites, which were much more rarely found as natural products, similarly show

• -methylalternariol (2), mostly referred to as alternariol 9-methyl ether, usually abbreviated with AME, and occasionally named djalonensone. It is almost as abundant as alternariol itself and it is hardly possible to catch up with the number of publications on this toxin; the SciFinder database gives at now more

• , 12, and 10 mm, respectively, at 50 μg/disk [148]. There is some evidence that not only alternariol and its 9-O-methyl ether can be present as sulfated conjugates, but that further toxins could similarly be sulfated in the organisms, e.g., altenusin and dehydroaltenusin [149]. Substituted alternariol

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• . Analytical thin-layer chromatography (TLC) was performed on aluminium plates coated with silica gel by using a suitable mixture of EtOAc and petroleum ether for development purpose. Column chromatography was performed by using silica gel (100–200 mesh) with an appropriate mixture of EtOAc and petroleum ether

• product which was then purified by silica gel column chromatography (as suitable mixture of ethyl acetate and petroleum ether) to give the anticipated products in 12 (85%), 15 (80%), and 17 (90%) yields. 1-(5,5,10,10,15,15-Hexabutyl-10,15-dihydro-5H-diindeno[1,2-a:1',2'-c]fluoren-2-yl)ethan-1-one (12

• ): White solid; yield 85%; (0.9 g, starting from 1 g of 10); Rf 0.50 (5% ethyl acetate/petroleum ether); mp 117–120 °C; 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J = 8.3 Hz, 1H), 8.38 (d, J = 6.2 Hz, 2H), 8.08 (s, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.48 (d, J = 7.5 Hz, 2H), 7.40 (p, J = 7.1 Hz, 4H), 2.97 (m, 6H

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

• of aryl sulfoxides with difluoroenoxysilanes as nucleophile under mild reaction conditions [46]. This provided access to organosulfur compounds ortho-functionalized by CF2H. At the same time Peng and co-workers described the dearomatization of aryl sulfoxides using the same difluoroenol silyl ether

• was mixed with a sufficient volume of a saturated NH4Cl solution, then extracted 3 times with diethyl ether. The combined organic layers were dried over MgSO4, filtered, concentrated under reduced pressure, and purified by preparative TLC or flash chromatography. [3,3]-Rearrangement of aryl sulfoxides

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

• vinyl ether enables the synthesis of 3-alkoxyalkenones 74, presenting an elegant route. Subsequently, these compounds undergo a three-component reaction with various hydrazines, forming 1,3-substituted pyrazoles 75 (Scheme 26) [104]. However, one limitation is the formation of 1,5-substituted pyrazoles

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

• solvent for ethyl glyoxylate phenylhydrazone 72a while methyl tert-butyl ether was preferred for aromatic and aliphatic aldehyde-derived hydrazones 72b. Styrenes, enamines as well as electron poor aliphatic alkenes were all suitable dipolarophiles. From a mechanistic point of view, the authors proposed

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• synthesis of 1,2-difluoroethylene based on perfluoropropyl vinyl ether as starting material can be found (Scheme 7). Consequently, two methods to prepare 1,2-difluoroethylene in the laboratory have been described to date. Even though at least five approaches to HFO-1132 can be found in patent literature, it

• -Difluoroethylene synthesis from perfluoropropyl vinyl ether. Deuteration reaction of 1,2-difluoroethylene. Halogen addition to 1,2-difluoroethylene. Hypohalite addition to 1,2-difluoroethylene. N-Bromobis(trifluoromethyl)amine addition to 1,2-difluoroethylene. N-Chloroimidobis(sulfonyl fluoride) addition to 1,2

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

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

• -lactone motif on an estradiol backbone [17]. Beginning with the 7α-alkanamidoestrone derivative 17, a nucleophilic addition by the anion of the THP propargyl ether occurred stereoselectively and provided the alkyne 18 in a 75% yield. Afterwards, the catalytic hydrogenation of the alkyne with a 1:1 mixture

• ether 39, a ring-closing enyne metathesis (RCEYM) was initiated using the Grubbs second-generation catalyst (G-II) and high temperature to obtain the spiro 2,5-dihydrofuran derivative 40 in 76% yield. Additionally, when a dienophile such as N-phenylmaleimide was directly added to the same pot and

• (110a and 110b, respectively). These protected compounds were subjected to alkynylation using 4-THPO-1-butyne on the carbonyl group at C-17, yielding steroids 111. Subsequent catalytic hydrogenation of the triple bonds, followed by deprotection of the alcohols from their THP ether groups and oxidation

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

• oxidation with the incorporation of a ketone at the C13 position yielded brassicicene A (23). After conversion of 23 into the corresponding silyl enol ether, Rubottom oxidation allowed completion of the total synthesis of brassicicene R (24). As an effort to explore the biomimetic rearrangement, analogous

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

• -desmethyl coibamide A in solution has been demonstrated by Sable et al. [43]. The use of diazomethane in diethyl ether as methylating agent yielded the methylated synthetic coibamide A. All of the aforementioned methods are robust and well-established. However, they do have their drawbacks. The application

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• ]. These RiPP natural products encompass a wide range of structural scaffolds including cyclopeptide alkaloids that contain a phenolic ether-linkage and the lyciumin-type peptides that are composed of a crosslink between the Trp-indole-N and the carbon in another amino acid side chain or peptide backbone

• . jasminoides that directly match this FFFY sequence (Figure 6A). Like other members of the Rubiaceae family [7][34], the tyrosine that forms the ether linkage remains intact, and not oxidatively decarboxylated as seen in members of the Rhamnaceae family. It is also predicted to contain a dimethylation at the N

• . argentea (Figure 4). Unlike moroidins which are part of the stephanotic acid subclass of burpitides defined by the Trp-indole-C to carbon crosslink, the molecules from the A. bettzickiana seems to be cyclopeptide alkaloids with two tyrosine derived ether linkages that resemble selanine A isolated from

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• temperature. The crude reaction mixture was purified by silica gel (230–400 mesh) column chromatography (petroleum ether/EtOAc as the eluent) to give the product 3 or ent-3. Selected examples of drugs and bioactive molecules bearing a pyrazole core. Single crystal X-ray structure of ent-3ba (CCDC 2234286

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

• size of the alkyl side chain at the alpha position of arylacetic acids (9–16). These features offer great opportunities for the introduction of a wide range of functional groups, including bromide (9), boron (12), ether (13), nitrile (14), ester (15), and alkene (16) moieties, which are versatile

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• speculate that the solvation effect might be beneficial for stabilizing the condensation intermediate I and avoiding further unwanted conversions, e.g., nucleophilic attack of excessive benzylamine to the intermediate I. The following examination on solvents demonstrated that using ether solvents as the

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• one hour. After removing the solvent by rotatory evaporation at reduced pressure, the residue was subjected to column chromatography with a mixture of ethyl acetate and petroleum ether (v/v = 1:4) as eluent to give the pure product for analysis. Pentamethyl rel-(4R,4aR,4bS,8aS)-1-benzyl-8-cyclohexyl-4

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• Rouser et al. using an intramolecular Cannizzaro reaction to give the corresponding unsymmetrical acid–alcohol substituted crown ether derivatives 43–46. Good to excellent yields of the desymmetrized Cannizarro products 43–46 were obtained using Ba(OH)2 as the base, thus effecting efficient

• desymmetrization of crown ether dialdehydes (Scheme 17) [84]. Synthesis of natural products and pharmaceuticals Exploring intramolecular Cannizzaro reaction: The Cannizzaro reaction is a versatile synthetic tool with applications in the synthesis of natural products, fine chemicals, and pharmaceuticals. Its

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• presence of alkene, alkyne, halogen, and ether moieties. N-Boc-protected amines and esters also provided a good to excellent yield. Unfortunately, α,β-unsaturated carboxylic acids and aliphatic carboxylic acids were ineffective using this method. In 2024, Liu and co-workers [31] introduced a photocatalytic

• radical cation 81 and Mes–Acr because of the favorable π–π stacking. Ethyl vinyl ether, which is the most nucleophilic molecule in the reaction, combined with radical cation 81 to form the oxonium radical 82, which could proceed in two directions: 1) β-elimination, yielding radical 83 and 2) photoinduced

• breakdown of ethyl vinyl ether and trapping of ethanol, yielding radical 84. To regenerate the photocatalyst, PhSSPh functioned as an oxidant. After protonation upon the β-elimination step, PhS− contributed a hydrogen atom to both 83 and 84, alongside regeneration of the HAT catalyst. Lastly, the acetal

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• family members in bacteria and plants [4], these diterpenoids have four main structural differences: the number and location of oxidized carbons, the absence or presence of transannular ether bridges, the configuration (cis or trans) of the bicyclic ring fusion, and the presence and configuration (E or Z

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• precipitation with a hexane–ether mixture and was found to be of sufficient purity for spectroscopic analysis. If desired, the product can be crystallized from an EtOAc–MeOH mixture for further purification. On the other hand, compound 2a has also been previously investigated for its potential covalent prolyl

• transformations is the purification of the synthesized product, since these oils are non-volatile and non-polar. However, in this study, the choice of these materials as green solvents allows convenient isolation of the cycloadducts by precipitation followed by filtration with hexane or diethyl ether. Thus, IMDAF

• , the reaction mixture was cooled to room temperature and the desired product, 2a was precipitated after trituration with hexane. The obtained solid product was isolated by filtration under vacuum, washed with ether–hexane solvent mixture and dried at room temperature. If desired for further

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• two silyl enol ether moieties, can be regarded as masked dianions or electroneutral equivalents of 1,3-dicarbonyl dianions and react with the same regioselectivity [13][14][15][16][17][18][19][20][21][22]. Both free and masked dianions were studied extensively in my group for many years. 1,3-Bis

• (silyloxy)-1,3-butadienes are highly moisture sensitive compounds which can be prepared from the corresponding 1,3-dicarbonyl dianions in two steps. For example, diene 6a is available by silylation of 2 to give silyl enol ether 5 which is subsequently deprotonated by LDA and treated with

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• dioxide (15 mmol, 1.66 g). The reaction mixture was stirred under a nitrogen atmosphere at 80 °C for 3 h. Before the solvent was evaporated at reduced pressure using a rotary evaporator, TLC was performed to verify completion of the reaction using 7:3 petroleum ether/ethyl acetate as the eluent. Upon

• in a different round-bottom flask, and the solvent was evaporated in a rotary evaporator. The resulting solid was dissolved in DCM, and silica gel was added to the DCM layer. This slurry was subjected to column chromatography on silica gel (100–200 mesh) using petroleum ether and ethyl acetate as

• solid. The filtrate was evaporated and column-chromatographed on silica gel (100–200 mesh) using petroleum ether and ethyl acetate as an eluent. The initial yellowish orange fraction containing N1,N2-bis(2-methoxyphenyl)oxalamide, collected with 22% ethyl acetate, was recrystallized from a chloroform

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• product (23 mg). Finally, the crude product was purified by preparative TLC (petroleum ether/EtOAc 3:1) to give 27 as a yellow powdery solid (15 mg, 22%, 35% based on reacted 3, Scheme 8). Mp 180 °C (dec.); 1H NMR (700 MHz, CDCl3) δ 7.29 (m, 2H), 6.98 (m, 2H), 6.88 (s, 4H), 3.64 (s, 6H), 2.30 (s, 12H

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• dichlorophosphane 9 from commercially available PCl3 and ethyl vinyl ether using a previously published procedure [68]. Compound 9 reacted with 1 equiv of benzyl alcohol in absolute Et2O and pyridine at −78 °C, followed by quenching of the reaction mixture with H2O. This procedure provided phosphinate 10 in more