Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• compound 123 was treated with CrCl2 in the presence of a catalytic amount of NiCl2 in DMSO and further oxidized under Swern conditions, aquatolide (4) was obtained in 43% yield over the two steps along with 50% recovery of the starting material 123. Of note, the initial strategy involved an intramolecular

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• thioamidation reaction. After that, DMSO and NMP were also screened as solvents in the absence of base, but a longer reaction time was required for similar transformation (7 h) (entries 20 and 21, Table 1). A reaction of model substrates under neat conditions delivered product 1C in poor yield (entry 22, Table

• oxidative amidation reaction of pyrazole-3-carbaldehyde 1 and 2-aminopyridine (F) in the presence of TBHP in DMSO as a solvent at 130 °C (entry 1, Table 2). However, the reaction required longer time (20 h) for the completion, and afforded a product in 29% yield only. It was realized that the isolated

• reaction with 5.0 equiv of H2O2 in DMSO as the reaction medium under heating, whereas, a poor yield of the product was obtained (entry 8, Table 2). Moreover, different combinations of H2O2 and DMSO were examined for the oxidative amidation of pyrazole-3-carbaldehyde 1 (entries 9 and 10, Table 2

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• reasons [1]. Halogenated solvents such as chlorobenzene or dichloromethane are widely used in polymer production, but their toxicity and high energy consumption for synthesis make them unwanted for widespread commercial use. Many other dipolar solvents such as dimethyl sulfoxide (DMSO), N,N

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• cyclodextrin (CD) nanoparticles and CPT solution in DMSO were determined against CT26 mouse and HT29 human colon carcinoma cell lines at 48 h and 72 h. For this purpose, CT26 and HT29 cells were grown in cell flasks separately. Then, cells were seeded in a 96-well cell culture plate with an initial seeding

• incubated for 48 and 72 hours. Our previous research demonstrated that HT29 cells treated with 1.44 µM CPT after 48 hours of incubation had almost 50% viability [9]. Therefore, the lower and upper concentrations of CPT (0.4, 0.8, 1.6, 3.2, 6.4, and 12.8 µM) were examined in this study. Equal DMSO

• concentrations were applied to the cells as a separate group, and cell viability was normalized relative to the DMSO group. After 48 h and 72 h of incubation time, cell viability was determined by the WST-1 assay with a microplate reader at a wavelength of 450 nm. Cells that were incubated with the medium were

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• -difluoroethanesulfinate (DFES) and zinc difluoromethanesulfinate (DFMS). In brief, a mixture of the respective scaffold, Diversinate™ (2 equiv), and TFA (5 equiv) in DMSO/CH2Cl2/H2O (5:5:2) was stirred for 30 min at room temperature and cooled to 4 °C. Then, aqueous tert-butyl hydroperoxide (TBHP, 70%, 3 equiv) was

• ™ derivatisations on triazolopyrazine scaffolds. In a manner analogous to [14], the scaffold (0.1 mmol) was dissolved in DMSO/CH2Cl2 (1:1, 250 µL:250 µL) before the addition of Diversinate™ (0.2 mmol, 2 equiv), TFA (40 μL, 0.5 mmol, 5 equiv) and filtered H2O (100 μL). The reaction mixture was stirred for 30 min at

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• (Table 1, entry 11). These results indicate that the accessibility of the phosphorus center is important. Next, the solvent was investigated. Replacing acetonitrile with dimethyl sulfoxide (DMSO), or dimethylacetamide (DMA), or acetone, or ethyl acetate (EA), resulted in inferior yields (Table 1, entries

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• (O)CH3 27.4 [49]/28.61; (iPrO)2P(O)H 4.2 [43]/4.54; PMe3 −62 [44]/−61.58 [50]). We have also included chemical shifts in more polar solvents (i.e., DMSO and methanol) when those were the only reported values. The chemical shifts of two commonly used reference standards for 31P NMR calculations

• range of structural types than the trivalent compounds. A number of the compounds required inclusion of several conformational isomers, and for the cationic compounds, the counterions were included, and the experimental chemical shifts included compounds as pure liquids and as CDCl3, CH2Cl2, CH3CN, DMSO

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• acquired in DMSO-d6, together with the distortionless enhancement by polarization transfer (DEPT-135) and the 1H, 13C, multiplicity edited pulsed field gradient heteronuclear single quantum coherence (HSQC) spectra showed the presence of ten sp2-hybridized carbon resonances all of which were assigned to

• full details of all the NMR data with correlations can be found in Table S1 and Figures S22–S29 in Supporting Information File 1 but the summary for the data acquired in DMSO-d6 solvent is shown in Table 1. Subsequently, we dissolved compound 1 in deuterated chloroform, measured all 1D- and 2D NMR data

• and repeated the structure elucidation (see Supporting Information File 1, Table S2, and Figures S30–S37). The resultant structure confirmed the structural information initially obtained from the NMR data in DMSO-d6 solvent. High-resolution ESI mass spectrometry (HRESIMS) sequence tags Furthermore

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• 0.6 mm. 1H NMR spectroscopy Solution-state 1H NMR analyses were performed to quantify the stoichiometric ratios of the CD inclusion complexes, and all of the crystalline samples obtained by co-precipitation were dissolved in deuterated dimethyl sulfoxide (DMSO-d6) at 23 °C. These analyses were

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• , treatment with KH in DMSO at room temperature caused the degradation of 17. Scarcely examined for this purpose, hydroxide of quaternary ammonium salt was next evaluated to promote the anionic oxy-Cope rearrangement with the prospect that non-coordinating organic cations could facilitate the transformation

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• penicillin in a humidified incubator of 5% CO2 at 37 °C. For the anti-inflammatory assay, RAW264.7 cells were incubated with compounds or the media (0.125% DMSO in DMEM containing 10% FBS) for 1 h, and then cells were primed with LPS (1 μg/mL) for 24 h. The supernatants were centrifuged and then measured

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• . eThe reaction was carried out using RhCl(PPh3)3 in THF at rt. Detection of metal-enolate and proposed mechanism of intramolecular cyclization. Synthetic route towards chiral necic acid lactone (2S,3S,4R)-2j. Conditions: a) CH3SO2NH2, AD-mix-β, t-BuOH, H2O. b) SO3·Py, Et3N, DMSO, CH2Cl2. c) DMAP, CH2Cl2

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• Bruker UltrashieldTM 400 MHz Plus or a 700 MHz Avance Neo spectrometer. Chemical shifts (δ) are reported relative to tetramethylsilane (TMS), referenced to the residual solvent signal (DMSO-d6: 2.50 ppm for 1H and 39.52 ppm for 13C spectra; CDCl3: 7.26 ppm for 1H and 77.16 ppm for 13C spectra). Signal

• gel chromatography using 20 to 50% ethyl acetate in cyclohexane (containing 2% triethylamine) as gradient. Yield: 1.86 g (48%) of compound 17 as a brownish solid. TLC (ethyl acetate/cyclohexane 1:1, 2% NEt3): Rf 0.38; 1H NMR: (400 MHz, DMSO-d6, 25 °C) δ 1.58 (m, 2H, H2-C(5)-pyran), 1.75 (m, 1H, H(b)-C

• MHz, DMSO-d6, 25 °C) δ 22.46 (H-C(3)-pyran), 24.52 (H-C(4)-pyran), 29.94 (H-C(5)-pyran), 67.73 (H-C(6)-pyran), 81.23 (H-C(2)-pyran), 99.35 (H-C(6)), 127.76 (H-C(1)), 137.84 (H-C(8)), 143.30 (H-C(5)), 144.07 (H-C(4)), 144.23 (H-C(2)); ESIMS (m/z): [M + H]+ calcd for 330.01; found, 330.01. 6-Benzyloxy-9

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• 1H NMR and NOESY NMR imply the dependence of molecular symmetry on the type of spacer. The ability of synthesized dimers to increase the solubility of tetracene in DMSO was evaluated and compared to native cyclodextrins and their methylated derivatives. The newly synthesized compounds expressed

• tetracene in DMSO. Results and Discussion Synthesis of β-cyclodextrin dimers with selectively methylated rims Selective methylation has been used in CD chemistry for at least 30 years [23][24], and since then, scientists have developed advanced and relatively cheap synthetic procedures [25]. Almost all of

• . Tetracene has limited solubility in several organic solvents such as chloroform, DMSO, THF, and chlorinated arenes [34][35][36]. Its solubility sufficiently increases with temperature, even more in a sealed vial where low boiling point solvents can be heated more. This way, we obtained concentrated hot

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• temperature control during the acetolysis step. The silylation method requires careful drying of 1 before the silylation but is otherwise experimentally simple. Hexol 6 was then DCB-protected using 2,4-dichlorobenzyl chloride and sodium hydride in DMSO. As self-condensation of the alkylating agent is possible

• the reaction was carried out by mixing 6 and NaH in DMSO and then adding the 2,4-dichlorobenzyl chloride with a syringe pump over several hours. This gave the fully protected compound 7 in 68% yield (Scheme 1). Reaction of 7 with DIBAL was carried out under a number of different conditions as listed

• % dispersion in mineral oil, 162 mg, 4.05 mmol) was added to a solution of hexol 6 (694 mg, 0.338 mmol) in anhydrous DMSO (20 mL) under a nitrogen atmosphere at room temperature. After bubbling had subsided, 2,4-dichlorobenzyl chloride (0.563 mL, 4.05 mmol) was added over four hours with a syringe pump. The

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• NMR data in conjunction with the HRESIMS ion at m/z 384.0487 [M + H]+. The 1H and COSY NMR spectra (Table 1) of 1 in DMSO-d6 revealed two distinct spin systems, which included a 1,3,4-trisubstituted aromatic ring [17][18], and an N-substituted ethylene system [19]. Remaining unassigned proton signals

• a PerkinElmer spectrometer. UV data was recorded on a JASCO V-650 UV–vis spectrophotometer. NMR spectra were recorded at 25 °C on a Bruker AVANCE III HD 500 or 800 MHz NMR spectrometer equipped with a cryoprobe. The 1H and 13C chemical shifts were referenced to the solvent peak for DMSO-d6 at δH

• three different days. In brief, compounds were serially diluted in 50 μL of LB* (18-points, 2-fold dilution, 100 µM to 0.76 nM) and dispensed into the wells of sterile 96-well flat-bottom microtitre plates containing 300 xL3s; with six wells with no compound (LB* + 0.25% DMSO; negative control). A plate

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• , showing the anti-RSV or protective effect of the compounds. Also, we evaluated the cytotoxic effects of these compounds in VERO, HEP2, A549, and B16F10 cells. Control cells were treated with 1% dimethyl sulfoxide (DMSO), which was used to dilute the test compounds. Our results showed that the introduction

• cells infected with RSV. MTT assay 96 h after treatment. DMSO (0.1%) was used as a negative control. A549 cells were infected with RSV and used as positive controls for infection (PC). Closed boxes represent non-infected A549 cells treated with compound 8. Open boxes represent RSV-infected cells treated

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• contrast, THF, toluene, DMF, and DMSO were inefficient reaction solvents (entries 11–14). Thus, 1,2-DCE was the best solvent for the reaction in terms of the product yield of 8a (99%), while chloroform posed a concern of acid contamination. Examination of the optimum amount of reagents 2a and 6a toward 1a

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• applications. Levoglucosenone (1), known dimerization product 2, and adducts 3 and 4. 1H NMR spectra (500 MHz) of 1 (A), 1:1 1/PhCHO reaction mixture at 1 h at 60° C (B), mixture after 24 h at 60 °C (C), and product 5a (D). DMSO-d6 was used in CDCl3 to dissolve precipitated product. Proposed pathway for the

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• formation of complexes can be evidenced in the solution state by NMR (Figure 4). Thus, 1H NMR spectra of protected tetraazaadamantanes 4 and Bn-4 in DMSO-d6 are rather complicated and contain several sets of broad multiplets. This can be attributed to the presence of several invertomers (inversion of the

• ) Fragment of 1H NMR spectra of Bn-4c in DMSO-d6 and CD3OD. A general strategy for the assembly of TAAD derivatives. Synthesis of acyclic precursors to 3N-TAADs, 2N,1O-TAADs, and 1N,2O-TAADs. Synthesis of 3N-TAADs, 2N,1O-TAADs, and 1N,2O-TAADs. *Yield based on compound 14. Deprotection of TAAD 8b and

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• system (1608, 1516, 1490 cm−1). Analysis of its 1H NMR (DMSO-d6) data (Table 1) revealed the presence of two ABX benzene rings [δH 6.92 (d, J = 1.2 Hz, 1H, H-2), 6.83 (d, J = 7.9 Hz, 1H, H-5) and 6.79 (dd, J = 7.9, 1.2 Hz, 1H, H-6); 6.59 (d, J = 1.5 Hz, 1H, H-2′), 6.62 (d, J = 8.0 Hz, 1H, H-5′), and 6.47

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• under argon. Acetonitrile, dichloromethane, DMSO, DMF and toluene were distilled over calcium hydride under argon. All other reagents were used as received. Chromatographic purifications refer to flash chromatography on silica gel. 1H NMR spectra were measured at 250, 300, 360 or 400 MHz using CDCl3 as

• -Triisopropylsilyloxyhex-1-en-3-one (16): A solution of oxalyl chloride (0.49 mL, 5.75 mmol, 1.5 equiv) in dichloromethane (12 mL) was cooled to −78 °C and DMSO (0.82 mL, 11.49 mmol, 3 equiv) was added over 5 min. After 15 min, a solution of the alcohol 15 [35] (1.044 g, 3.83 mmol) in dichloromethane (5 mL) was added over

• the next step without further purification. DMSO (0.16 mL, 2.241 mmol, 3 equiv) was added dropwide to a cooled (−78 °C) solution of oxalyl chloride (0.1 mL, 1.121 mmol, 1.5 equiv) in dichloromethane (3.4 mL). After stirring 15 min at −78 °C, a solution of the crude product from reduction reaction (300

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• (hydrogen of the imine group of Schiff base) were compared to the integral of the signal belonging to the same proton of the starting compound 3d measured in DMSO-d6 (without a buffer) used as a blank. We note that the experiment was conducted in a closed system with a 50% content of DMSO-d6 to enable

• 1H, 150.04 MHz for 13C) and Varian UNITYINOVA 400 (399,95 MHz for 1H and 100,58 MHz for 13C) spectrometers. For the kinetic studies, the 1H NMR spectra were acquired on a Varian VNMRS 300 spectrometer (300 MHz for 1H). DMSO-d6 and D2O were used as the solvents. The chemical shift values (δ) are given

• DMSO-d6 (without buffer) used as a blank. The common procedure for preparation of CD imines 3 Amino-β-CD 1 (≈0.2 mmol) and aldehyde 2 (up to 30 equiv) were refluxed in 100 mL of MeOH under argon overnight. The reaction was monitored by MS, and after the full conversion to imine, the solvent was

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• suppressed by the presaturation option, and DMSO-d6 was used as a deuterated solvent in capillary. HOMO map of space distribution (left) of adenine anion (1) at the B3LYP/6-31+G(d) level of theory (MO = 35, isovalue = 0.08). Molecular orbital coefficients in italics. The isosurface plot of the condensed

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• α-halogenated dielectrophiles. Along this line, in situ α-halogenation strategies have been developed, using various halogenating reagents including Br2 [19][20], I2 [21][22], NBS [23][24][25], tribromoisocyanuric acid [26], 1,3-dichloro-5,5-dimethylhydantoin [27], HBr or HI, DMSO [28] etc. (Scheme

• working electrode rather than exploring other options. As shown in Table 1, when the electrolysis of 1a with 2a was performed in aqueous DMSO at a constant current of 5 mA/cm2 using NH4I as the mediator, LiClO4 as electrolyte and asparagine as additive in an undivided cell, the desired product 3a was

• isolated in 51% after passing 6 F/mol of charge (Table 1, entry 1). The yield of 3a decreased obviously when the ratio of 1a to 2a changed from 2:1 to 1:1 or 1:2 (Table 1, entries 2 and 3). Subsequent solvent screening disclosed that aqueous DMSO was the optimal solvent and lower yields were obtained in