Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• ) [63]. Glacial acetic acid (AcOH) was initially selected as a hydrophilic (polar) protic solvent due to its high dipole moment, which makes it ideal for microwave reactions, as well as its ability to facilitate simple work-up procedures by simple addition of water [64]. Using sodium acetate (NaOAc) as

• . Additionally, some substrates proved incompatible with this reaction protocol. 2-Carboxybenzaldehyde did not result in the recovery of any solid product by simple filtration, probably due to its high solubility in water. Use of aliphatic aldehydes presented a significant challenge, as only the product 3z from

• aldehyde 1, activated by protonation of the oxygen atom through structure ii, forming the intermediate aldol iii. In the presence of EDDA, water elimination occurs in intermediate iv, yielding the Knoevenagel adducts 3 or 4. Synthesis of novel imidazo[1,2-a]pyridine–thiazolidinone hybrids To further

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• –220 nm and a maximum below 200 nm. CD spectroscopy revealed that cyclic topology shifts characteristic peaks and stabilizes secondary structures through cooperative ring size/sequence/solvent effects [30]. TFE disrupts the hydrogen-bonding network of water, reduces solvent polarity, and enhances the

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• their concentrations, particularly in water. To maintain anion levels within acceptable ranges, their removal from the environment is often necessary [1][2]. Current technologies for removing anions from aqueous solutions include chemical coprecipitation [3], ion-exchange [4], or membrane filtration [5

• example, an amphiphilic poly(methyl methacrylate)-based polymer modified with calix[4]pyrrole was found to form micelles in water that capture anions from caesium salts and can be precipitated from solution upon heating [11]. Similarly, a hydrogel composed of poly(vinyl alcohol) cross-linked by a “Texas

• -sized” molecular box has been used to extract various anions from water [12]. Another family of macrocyclic compounds suitable for anion recognition and binding are bambusurils (BUs). BUs act as very potent anion receptors in both organic solvents and water. Furthermore, their portals can be variously

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• follows: Commercially available compounds 31 and 32 were converted to the C2-symmetric 33 over 13 steps, enabling construction of the AB bicyclic skeleton in the target molecules. Compound 33 then underwent Mukaiyama hydration to adjust the C15 oxidation state, followed by water-promoted consecutive

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• -NH2). Size and zeta potential measurements: DLS and ELS measurements were performed on a sample of compound 3 (1 mg) dissolved in 1 mL pure water. The colloidal solution was centrifuged at 10,000 rpm for 10 min and the supernatant was collected and analyzed by a Zetasizer NanoZS90 analyzer (Malvern

• of compound 3 in DMSO-d6 (400.13 MHz, 297 K). Intensity-weighted mean hydrodynamic diameter (left), and zeta potential distribution (right) of compound 3 (1 mg/mL water), after vortex and sonication. Antiproliferative effects by compound 3 and its chemical precursor 1. A) Results on proliferative

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• -methyltriazolium (MTA) group. The amphiphilic spacer carries an ortho-dimethoxybenzene group on each side as stoppers to prevent the macrocycle from slipping off. These stoppers are connected to terminal polyethylene glycol (PEG) chains designed to interact with the membrane–water interface (Figure 1). Effect of

• transition to a more ordered membrane. EYPC/Chol bilayers form liquid-ordered (Lo) phases, characterized by increased thickness, rigidity, and reduced water permeability [16]. In EYPC/Chol 8:2 LUVs, rotaxane 1-E induced 29% release, more than rotaxane 1-Z, which caused only 16% release (Table 1, Figure 4a

• previous molecular dynamics simulations of rotaxane 1 in POPC bilayers, a major component of EYPC [16], showed that rotaxane 1 disrupts lipid packing and promotes water accumulation within the bilayer [15]. These effects enhance membrane permeability to hydrophilic molecules such as sulforhodamine B. The

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• the nucleophilic substitution of the nitro group in 2-nitrobenzonitriles using Na2S in a DMF/water medium, followed by alkylation of the resulting 2-cyanophenylthiolates and subsequent cyclization [31]. However, in our case, the reaction of ester 1 with Na2S in either acetone or a DMF/water mixture

• reactions, probably involving ester hydrolysis or alkylating agent decomposition, can be avoided by omitting the external base. In addition, Na2S2O4 was investigated as a reductant in a DMF/water 9:1 (v/v) mixture at room temperature (Table 2, entry 6). In the presence of both K2CO3 and the alkylating agent

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• ] and vaccines [15][16][17][18]. That is why new efficient and stereoselective methods for the synthesis of both Galf-containing mono- and oligosaccharide derivatives are highly demanded. It is a well-known fact that galactofuranose form constitutes only 5% in water solution of unprotected ᴅ-galactose

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• 30% and a selectivity of 70% at −100 °C (Scheme 21). 2.3 Wolff rearrangement The Wolff rearrangement is the transformation of α-diazoketones into acids or their derivatives through heating, catalysis, or UV irradiation in the presence of water, alcohols, ammonia, amines, etc. The Wolff rearrangement

• ketone 154 with UV-C (200–280 nm) light yielded approximately equal amounts of products 155 and 156 (1.25:1 after 85% conversion). In the presence of water (CH3CN/H2O 10:1), a crystalline cyclooctene compound 157 was obtained by irradiation of 154. However, compound 156 was not detected. When irradiating

• 154 with UV-A (315–400 nm) in the presence of water (CH3CN/H2O 10:1), cycloheptene compound 158 was obtained, but compound 155 could not be detected. These results are consistent with the selective conversion of ketone 155 to acid 158 by UV-A irradiation and the selective transformation of ketone 156

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• , toxicity, pesticide similarity, and biodegradability of methyl laurate in comparison with a series of conventional organic solvents, water, some fatty acids and their derivatives. The findings of this investigation revealed that methyl laurate exhibited better green solvent properties when evaluated

• troublesome [21][22]. It is evident that this class of solvents may be accompanied by a number of drawbacks. For instance, they are frequently expensive, exhibit negligible or non-existent biodegradability, and there is a lack of data concerning their potential toxicity. Conversely, while water is regarded as

• involved a comparative analysis of these vegetable oils and derivatives with water and a range of commonly employed organic solvents in organic transformations. Results and Discussion The requisite starting compounds, nitrones 1a–f and a selection of N-substituted maleimide derivatives 2b–d were

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• base results in the deprotonation of the ammonium site and shuttling of the macrocycle to the urea site. Whereas, upon addition of acid, the macrocycle returns to the protonated BAA site. Notably, the rotaxane exhibited high fluorescence intensity due to aggregation in acetonitrile with high water

• cannot undergo the photocyclization reaction when the macrocycle is in the BAA site due to conformational restraint. This system was used to form water-soluble nanoparticles to investigate their biological applications. The obtained nanoparticles exhibited bright red photoluminescence and the ability to

• revealed that while azobenzene photoisomerization can directly induce some degree of lipid packing reorganization, the dominant effect arises from changes in the position of the rotaxane within the membrane. Specifically, in the trans isomer, the macrocycle resides closer to the membrane–water interface

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• Suvenika Perera Peter Y. Zavalij Lyle Isaacs Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States 10.3762/bjoc.21.176 Abstract Contamination of water bodies by micropollutants including industrial dyes is a worldwide health and

• environmental concern. We report the design, synthesis, and characterization of a series of methylene-bridged glycoluril dimers G2W1–G2W4 that are insoluble in water and that differ in the nature of their aromatic sidewalls (G2W4: benzene, G2W3: naphthalene, G2W1 and G2W2: triphenylene). We tested G2W1–G2W4

• receptor (nAChR) by a pharmacokinetic approach [1][2]. Contamination of water bodies by the improper disposal of consumer and industrial chemicals constitutes a significant threat to the health of both humans and animals [3]. Dyes are a significant class of water pollutants which are commonly used by the

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• radical initiated intramolecular cascade cyclization of 1,n-enynes to provide structurally diverse heterocycles (Scheme 4) [11]. Solvent selection dictated divergent reaction pathways under I2/TBHP oxidation. When an acetonitrile/water mixed solvent was used, iodine radical addition to the alkyne

• and co-workers achieved an innovative gold-catalyzed cascade cycloisomerization of 3-allyloxy-1,6-diynes to access cyclopropane- and cyclobutane-fused benzofurans/chromanols (Scheme 5) [12]. In this study, solvent polarity and trace water were identified as key parameters governing the reaction

• pathway. In THF with trace water, water served as a nucleophile that participated in the reaction, triggering hydroxylation of cyclopropanation intermediate 19 and affording cyclopropane-fused chromanol products 20 (Scheme 5, path a). In anhydrous 1,2-dichloroethane (DCE), gold(I)-catalyzed

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• the presence of water, highlighting its robustness. Keywords: azo compounds; cross-coupling; domino catalysis; palladium; phosphine ligands; Introduction Azobenzenes are a widely studied class of compounds known for their distinctive photoresponsive properties, rendering them valuable in a variety

• batch of Cs2CO3 showed a dramatic reduction in product yield (Table 1, entry 12). Control experiments with varying amounts of water (0–10 equiv) demonstrated that a small amount of water is crucial for the reaction (Supporting Information File 1, Table S7 and Table 1, entry 11). This effect, previously

• addition of 2 equivalents of water (Table 1, entries 12 and 13). Finally, the oxidant t-Bu-OO-t-Bu could be replaced by O2, yielding compound 3a with GC yields of up to 79% (Table 1, entry 14, 75% isolated yield). In reactions giving <70% isolated yield, no single side-product dominates; the missing mass

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• KGaA, Darmstadt, Germany), adjusting the pH with HCl. Water for buffer and eluent preparation were provided by a Millipore Milli-Q water purification system. Kinetic aqueous solubility assay. All compounds were dissolved in DMSO to make stock solutions at 10 mM concentration. In the case of 7i, 7j, and

• ). Analytical methods. All samples of the kinetic solubility and in vitro permeability assays were analyzed on a Waters Alliance 2695 Separations Module equipped with a 2996 PDA detector, using a Water Xterra RP 18 chromatographic column (100 × 4.6 mm, 3.5 µm) at 45 °C, applying 1.2 mL/min flow rate. For a 7

• -minute long gradient program, eluents A (0.1% formic acid in water) and B (0.1% formic acid in acetonitrile) were used as follows: initial conditions with 30% B were kept for 1 minute, then 90% B was achieved within 3 minutes, kept for further 1 minute, finally the initial condition was adjusted and

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• cationic resonance G quickly. The nucleophilic attack of D2O formed H, which underwent dedeuteration and elimination of DI to form 30a with reduction of deuterated water to generate deuteroxyl ions (OD−) and deuterium gas (D2) at the cathode. This method, using iodide salts as electrolyte and redox

• reaction of nitrile, xanthene, terminal alkyne and water to synthesize oxazole was established by Li in 2023 (Scheme 12) [219]. After examining the reaction carefully, the optimized reaction conditions were obtained as follows: a mixture of alkyne 31 (0.3 mmol), xanthene 32 (0.45 mmol), CH3CN (5.0 mL), H2O

• (Scheme 13) [255]. Under electrolysis (graphite as electrodes, tetra-n-butylammonium salt (TBAPF6) as electrolyte, N,N,N,N-tetramethylethylenediamine (TMEDA) as mediator, 4.28 V), the four-component reaction of alkynes 35, NaSO2CF3, nitriles and residual water proceeded efficiently to form titled

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

• ·6H2O/meglumine (N-methylglucamine) was found effective. This DES system proved to be a fully water compatible medium for the three-component conversion of glycolaldehyde, allowing the synthesis of a variety of 3-(indol-3-yl)-2,3-dihydrofurans in good yields. Interestingly, the DES (FeCl3·6H2O/meglumine

• than nine steps and gave only 15% yield. No remaining acetal was found in the final product (Scheme 18). The production of lactic acid from dihydroxyacetone or its derivative pyruvaldehyde was investigated on large scale to evaluate the water tolerance of Lewis acid sites of several solid catalysts [86

• co-workers developed an electrocatalytic strategy for the synthesis of HFO from furfural [111]. The very important and key bioactive compound HFO was formed by using water as an oxygen source and chalcogenides such as CuS, ZnS, or PbS as electrocatalysts. CuS nanosheets gave the best performance

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• -aryl-2-(tert-butylamino)-2-oxoethyl)amino)-4,5-dioxopentanoic acids 5a–l in 50–81% yields (Scheme 2, pathway A; Table 1). The compounds 5a–l were isolated easily by adding water to the reaction mass until it became cloudy, whereupon a precipitate of the product was formed and isolated (all experimental

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

• with organic reactions, this chemo-enzymatic strategy has been successfully utilized in the synthesis of complex molecules [22][23]. Enzymatic reactions feature a convenient operation due to their relative insensitivity to water and oxygen, as well as a specificity to certain substrates, resulting in

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• reactions, a product with molecular weight consistent with O–H insertion into water was also observed. For these 18 substrate/co-substrate combinations, the reaction with the highest estimated yield was selected for mass-directed purification (Table 2). In total, 23 intermolecular reaction products were

• isolated and structurally characterised (using, where appropriate, HMBC, COSY and nOe NMR methods; see Figure 3). In general, the yields of these products were rather low, which may stem from poor (co-)substrate solubility in some cases; and/or competitive O–H insertion into adventitious water. On the

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• total charge of 2.2 F/mol was delivered. The reaction mixture was poured into a beaker with 10 mL of distilled water, and a saturated solution of NaHCO3 was added to adjust the pH to ≈7. 10 mL of ethyl acetate were then added, and the two phases were separated. The aqueous phase was then extracted with

• experiments were conducted until a total charge of 4.15 F/mol was delivered. The reaction mixture was then poured into a beaker with distilled water, and a saturated solution of NaHCO3 was added to adjust the pH to ≈7. Ethyl acetate was added, and the two phases were separated. The aqueous phase was then

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• believed to be coordinatively unsaturated zincs at the MOF surfaces, and their lipophilization resulted in a greater than ten-fold increase in the initial rate of the reaction [31]. The promotion of this reaction was attributed to the repulsion of the water by-product by the lipophilic surface, thereby

• catalysis have focused on lipophilization to prevent water-based catalyst decomposition, with only a few investigating how lipophilic pores surfaces can increase catalyst efficiency [32][33], despite enzymes employing such a strategy. The lipophilicity of enzyme active sites tends to improve reaction rates

• by increasing the binding affinity for the lipophilic reactants and by decreasing the energy required to desolvate acid/base amino acid catalysts [34][35]. Lipophilicity has also been found to be beneficial in condensation reactions as the removed water molecules are repelled by the hydrophobic

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• concentration of the photoswitch in solution: when MeOH or water are present, the lifetimes drop significantly, and particularly at pH 4, as consequence of more favourable intermolecular proton transfer. Calculations show that water molecules bridging between two Z-isomers favour the formation of hydrazone and

• the E-chair isomer [51]. All the compounds show excellent resistance to fatigue. The behaviour of some (hetero)diazocines was also studied in water and solvent mixtures [50][51]. Interestingly, N-acetyl-diazocine possesses overall comparable properties and a longer thermal half-life, and it is also

• soluble in water. For C- and S-diazocine, the absorption band separation of the two isomers is lower in polar solvents, resulting in worse PSS. In particular, for the S-diazocine it was found that the E-chair conformer was bathochromically shifted with increasing polarity of the solvent until completely

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• ease of modification [42]. Among these, CAs and PAs are representative aromatic macrocycles. They can be made water-soluble and exhibit good biocompatibility through carboxyl or phosphate group modification, showing great potential in biomedical carrier applications. Compared with other artificial

• molecules and high-selectivity binding in drug-controlled release. Many calix/pillar[n]arene hosts are soluble in water, particularly macrocycles that are modified with carboxyl and phosphate groups. Moreover, their amphiphilic modification ability allows easy self-assembly into functional materials like

• solubility, this can be improved through derivatization. Water-soluble calixarene derivatives can be obtained through functional modifications, including the introduction of sulfonic acid, amine, and carboxylic acid groups [57][58][59]. These water soluble macrocycle derivatives can be used to increase the

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• of EDC permits easy removal of the water-soluble urea-based byproduct with an aqueous wash as opposed to the hydrophobic dicyclohexylurea arising when DCC is utilized, which is more difficult to separate from the hydrophobic malassezione. This route should afford ready access to malassezione for

• with EtOAc (3 × 50 mL) and the combined organic layers were washed with water (100 mL) and brine (100 mL), and then dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel (EtOAc/hexane gradient 1:10 → 1:1, 1% AcOH

• , 0.7mmol, 0.2 equiv) in THF (10 mL) under an argon atmosphere. The reaction mixture was stirred at room temperature for 12 h. After completion of the reaction, the solvent was removed under reduced pressure. The crude reaction mixture was then diluted with EtOAc (100 mL) and washed with water (2 × 40 mL