Thiazolium salt-catalyzed [3 + 2 + 1] cyclization for the synthesis of trisubstituted 2-pyrones using arylglyoxals as a carbonyl source

Li-Chen Xu, Peng Zhou, Jia-Zhuo Li, Wen-Juan Hao, Shu-Jiang Tu* and Bo Jiang*
School of Chemistry & Materials Science, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, P. R. China. E-mail: wjhao@jsnu.edu.cn; jiangchem@jsnu.edu.cn; Fax: +8651683500065; Tel: +8651683500065

Received 2nd October 2017 , Accepted 13th November 2017

First published on 14th November 2017


A new thiazolium salt-catalyzed [3 + 2 + 1] cyclization of acetylenedicarboxylates with arylglyoxals has been developed, enabling organocatalytic umpolung to access trisubstituted 2-pyrones with good yields via C–C bond cleavage, in which arylglyoxals played dual roles as a ring component as well as a carbonyl source. The reaction mechanism was proposed based on LC-MS analysis.


Introduction

2-Pyrones are an important class of lactones that are extremely prevalent in many natural products and biologically active substances.1 Compounds incorporating a 2-pyrone core structure have been found to exhibit a broad spectrum of biological and pharmacological activities including anti-HIV,2 antimicrobial,3 anti-inflammatory,4 anticancer,5 and antifungal.6 Alongside their biological significance, 2-pyrones are also widely used as synthetic intermediates in cycloaddition and ring-opening reactions,7 owing to their high reactivity caused by the conjugated diene and lactone functionalities. With these contributions in mind, many efforts have been devoted to developing an efficient incorporation of a 2-pyrone unit into organic and medicinal targets. Generally, strategies for α-pyrone syntheses include multistep lactonization/cyclization of β-ketoesters,8 oxidation of diarylcyclopentenones,9 N-heterocyclic carbene catalyzed ring expansion,10 transannulation of 1,3-dioxin-4-ones,11 Pd,12 Au,13 Rh,14 Ru,15 and Ni16 catalyzed annulation reactions, and other methods.17 Recently, Smith et al. reported an isothiourea-mediated [4 + 2] cyclization cascade of (phenylthio)acetic acids and α,β-unsaturated trifluoromethyl ketones for the formation of functionalized 2-pyrones18 (Scheme 1a). Later, Zhang and co-workers developed a base-promoted carboxylative cyclization of propenyl ketones with carbon dioxide to synthesize polysubstituted 2-pyrones via γ-carboxylation (Scheme 1b).19 Despite all these significant achievements, organocatalytic [3 + 2 + 1] cyclization cascade toward poly-substituted 2-pyrones via an umpolung process using arylglyoxals as a carbonyl source, to the best of our knowledge, remains unexploited so far.
image file: c7qo00899f-s1.tif
Scheme 1 Profiles of cyclization for 2-pyrone synthesis.

On the other hand, thiazole carbenes as N-heterocyclic carbene (NHC) catalysts have attracted considerable attention in chemical science, enabling the direct polarity reversal of aldehydes to construct various unusual C–C bonds.20 Over the past few decades, thiazole carbene catalyzed transformations have been widely studied.21 Notably, thiazole carbenes could serve as reaction substrates for the synthesis of heterocycles. Ma et al. presented thiazolium-mediated three-component reactions of dimethyl acetylenedicarboxylate (DMAD) and aldehydes, providing 3-aminofuran derivatives22 (Scheme 1c). Enlightened by these interesting transformations and our recent findings on cyclization reactions of arylglyoxals,23 we considered to employ arylglyoxals to replace aldehydes in the system described above to evaluate the feasibility of 3-aminofuran synthesis. The reaction in acetonitrile proceeded smoothly in the presence of NaH. Interestingly, instead of 3-aminofuran derivatives, the reaction occurred in an unprecedented umpolung direction/C–C cleavage to generate tri-substituted 2-pyrones of chemical and biomedical importance, in which thiazole carbene only acted as a NHC catalyst rather than a reaction component (Scheme 1d). Herein we elaborated this special and practical transformation in which arylglyoxals played dual roles as a ring component as well as a carbonyl source.

Results and discussion

At the outset of our studies, DMAD 1a and 2,2-dihydroxy-1-(4-methoxyphenyl)ethanone (p-methoxyphenyl = PMP, 2a) were selected as the model substrates and subjected to the reaction in CH3CN using 20 mol% of thiazolium salt I (3-ethyl-5-(2-hydroxyethyl)-4-methylthiazol-3-ium bromide) as a catalyst and NaH as a base at 100 °C under air conditions (Table 1, entry 1). The reaction proceeded readily to access unexpected 2-pyrone 3a in 64% yield. Exchanging thiazolium salt I for II (5-(2-hydroxyethyl)-3,4-dimethylthiazol-3-ium iodide), III (3-benzyl-5-(2-hydroxyethyl)-4-methylthiazol-3-ium chloride), or IV (6,7-dihydro-2-pentafluorophenyl-5H-pyrrolo[2,1-c][1,2,4]triazolium tetrafluoroborate) led to lower yields of product 3a as compared with catalyst I (entry 1 vs. entries 2–4). An increase in thiazolium salt I loading (30 mol%) remarkably facilitated this reaction and afforded a higher 82% yield (entry 5). The yield of 3a levelled off when the loading of catalyst I was further increased to 40 mol% (entry 6). Changing the amount of base did not enhance the reaction yield (entries 7 and 8). We next optimized the conditions by using different bases such as Et3N, DBU, K2CO3, Cs2CO3, t-BuOLi, and t-BuOK that are often employed in carbene catalysis. The results indicated that all these bases could promote the conversion of 1a and 2a into 3a, but <65% yield was observed (entries 9–14). By taking the combination of thiazolium salt I with NaH, we then investigated the solvent effect by using other aprotic solvents, such as 1,2-dichloroethane (DCE), ethyl acetate (EA), 1,4-dioxane, and EtOH, showing that all these solvents completely suppressed the reaction process as only a trace amount of 3a was detected (entries 15–18). Moreover, the reaction could work at either 80 °C or 120 °C, but still gave slightly inferior outcomes as compared with the reaction temperature being 100 °C (entry 5 vs. entries 19 and 20).
Table 1 Optimization of the reaction conditionsa

image file: c7qo00899f-u1.tif

Entry Base (equiv.) Cat (mol%) Solvent Yieldb (%)
a Reaction conditions: 1a (0.3 mmol, 3.0 equiv.), 2a (0.2 mmol, 1.0 equiv.), catalyst (x mol%), solvent (3.0 mL), air, 120 °C.b Isolated yield based on 2a.c 80 °C.d 120 °C.
1 NaH (2.0) I (20) CH3CN 64
2 NaH (2.0) II (20) CH3CN 48
3 NaH (2.0) III (20) CH3CN 32
4 NaH (2.0) IV (20) CH3CN 28
5 NaH (2.0) I (30) CH3CN 82
6 NaH (2.0) I (40) CH3CN 81
7 NaH (1.0) I (30) CH3CN 49
8 NaH (3.0) I (30) CH3CN 72
9 Et3N (2.0) I (30) CH3CN 15
10 DBU (2.0) I (30) CH3CN 65
11 K2CO3 (2.0) I (30) CH3CN 40
12 Cs2CO3 (2.0) I (30) CH3CN 46
13 t-BuOLi (2.0) I (30) CH3CN 46
14 t-BuOK (2.0) I (30) CH3CN 43
15 NaH (2.0) I (30) DCE Trace
16 NaH (2.0) I (30) EA Trace
17 NaH (2.0) I (30) 1,4-Dioxane Trace
18 NaH (2.0) I (30) EtOH Trace
19 NaH (2.0) I (30) CH3CN 62c
20 NaH (2.0) I (30) CH3CN 67d


With these optimal reaction conditions in hand, we then systematically investigated the generality of this thiazolium salt-catalyzed [3 + 2 + 1] cyclization toward densely functionalized 2-pyrones 3 by evaluating acetylenedicarboxylate and arylglyoxal components (Scheme 2). Arylglyoxals with diverse functionalities were first examined in combination with substrate 1a. Various substituents of electronically rich, neutral and poor nature present on the aryl ring of 2 were proven to be perfectly tolerated under the current catalytic conditions, accessing in all cases good yields of 3b–3l. Functional groups like methoxy (2b), ethoxy (2c), methyl (2d), ethyl (2e), fluoride (2g), chloride (2h and 2i), bromide (2j) and trifluoromethyl (2k) would be accommodated. Among them, as the p-fluorophenyl counterpart (2g) was adopted as both a ring component and a carbonyl source, an increase in the yield was obtained (3g, 76%), whereas the 4-trifluoromethylphenyl group resulted in a significantly reduced yield (3k, 34%). The reaction also worked effectively with substrate 2l bearing a sterically encumbered 2-naphthyl (2-Np) group giving its product 3l in 64% yield. Similarly, diethyl acetylenedicarboxylate 1b was found to be an efficient reaction partner, enabling catalytic [3 + 2 + 1] cyclization/C–C cleavage cascades to access richly decorated 2-pyrones 3m–3v with yields ranging from 59% to 80%. It is noteworthy that the current catalytic protocol represents a new and practical pathway for assembling polysubstituted 2-pyrones with multiple carbonyl units through an umpolung strategy involving C–C bond cleavage of arylglyoxals. In the case of 3a, its structure was unequivocally confirmed by carrying out single-crystal X-ray diffraction (Fig. 1 and see the ESI).


image file: c7qo00899f-s2.tif
Scheme 2 Domino synthesis of pyrazol-4-ones 3. (i) Reaction conditions: Acetylenedicarboxylate 1 (0.30 mmol), arylglyoxals 2 (0.2 mmol), cat. I (30 mol%) and MeCN (3.0 mL) at 100 °C for 2 hours.

image file: c7qo00899f-f1.tif
Fig. 1 X-Ray structure of 3a.

On the basis of literature reports20–22 and from the observations of the experimental results, we believe that the nucleophilicity of thiazole carbenes plays a pivotal role in the success of the whole cascade reaction sequence. A reasonable mechanism for the present cyclization reaction is proposed as shown in Scheme 3. First, thiazole carbene A, generated in situ by the deprotonation of the thiazolium salt at its most acidic position,20 reacts with 2-(4-methoxyphenyl)-2-oxoacetaldehyde B derived from substrate 2a to form zwitterionic intermediate C (detected by LC-MS, MS = 335.1), followed by the umpolung process to convert into intermediate D. Next, the addition of D into the C[triple bond, length as m-dash]C bond of substrate 1a generates zwitterionic intermediate E (detected by LC-MS, MS = 477.1), which undergoes an aldol-type reaction with B to deliver intermediate F (detected by LC-MS, MS = 641.2). Afterward, proton transfer (P.T.) between F and H2O gives intermediate G (detected by LC-MS, MS = 642.2), intercepted by the hydroxyl anion to afford H, which eliminates 4-methoxybenzoic acid (detected by LC-MS, MS = 152.0) to give I (detected by LC-MS, MS = 507.2). Intermediate I is converted into the final product 3a through a continuous intramolecular nucleophilic addition/elimination of thiazole carbene A/dehydration sequence.


image file: c7qo00899f-s3.tif
Scheme 3 Proposed mechanism for forming products 3.

Conclusions

In conclusion, starting from acetylenedicarboxylates and arylglyoxals, we have developed thiazolium salt-catalyzed [3 + 2 + 1] cyclization for the synthesis of structurally diverse 2-pyrones with generally good yields. The present organocatalytic umpolung provides a special and reliable protocol for constructing a trisubstituted 2-pyrone framework via C–C bond cleavage, in which arylglyoxals played dual roles as a ring component as well as a carbonyl source. Further assessment of the bioactivity of these 2-pyrone compounds is underway in our laboratory.

Experimental

General information

All one-pot reactions were carried out in a 10 mL Schlenk tube equipped with a magnetic stir bar under air conditions. All melting points are uncorrected. The NMR spectra were recorded in CDCl3 or DMSO-d6 on a 400 MHz instrument with TMS as an internal standard. Chemical shifts (δ) are reported in ppm with respect to TMS. Data are represented as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet), coupling constant (J, Hz) and integration. HRMS analyses were carried out using a TOF-MS instrument with an ESI source. X-Ray crystallographic analysis was performed with a SMART CCD and a P4 diffractometer.

General procedure for the preparation of products 3

Example for the synthesis of 3a. A mixture of dimethyl but-2-ynedioate (1a, 0.3 mmol, 42.6 mg), 2,2-dihydroxy-1-(4-methoxyphenyl)ethanone (2a, 0.2 mmol, 36.4 mg), 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazol-3-ium bromide (0.03 mmol, 7.6 mg), NaH (0.2 mmol, 4.8 mg) and MeCN (3.0 mL) was added in a 10 mL reaction vial, which was sealed and heated at 100 °C until TLC (petroleum ether[thin space (1/6-em)]:[thin space (1/6-em)]ethyl acetate 2[thin space (1/6-em)]:[thin space (1/6-em)]1) revealed that the conversion of the starting material 2a was complete. Then the reaction mixture was cooled to indoor temperature and the obtained product was dissolved in CH2Cl2 and acetone. After that, the organic phase was concentrated by vacuum distillation and was purified by flash column chromatography (silica gel, mixtures of petroleum ether/acetic ester, 10[thin space (1/6-em)]:[thin space (1/6-em)]1, v/v) to afford the desired pure products as yellow solids.
Dimethyl 6-(4-methoxyphenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3a). Yellow solid; mp: 99–101 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.0 (d, J = 8.8 Hz, 2H, Ar–H), 7.24 (s, 1H, Ar–H), 7.12 (d, J = 9.2 Hz, 2H, Ar–H), 3.89 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 3.81 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ 164.6, 164.0, 163.1, 163.0, 158.3, 146.7, 128.7, 122.8, 115.3, 98.8, 56.1, 54.0, 53.3. IR (KBr, ν, cm−1): 2956, 1746, 1732, 1620, 1514, 1431, 1280, 1117, 1022, 931. HRMS (ESI): m/z calcd for: C16H14O7Na, 341.0637 [M + Na]+; found: 341.0648.
Dimethyl 6-(3,4-dimethoxyphenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3b). Yellow solid; mp: 185–187 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.62–7.59 (m, 1H, Ar–H), 7.48 (d, J = 2.4 Hz, 1H, Ar–H), 7.33 (s, 1H, Ar–H), 7.14 (d, J = 8.4 Hz, 1H, Ar–H), 3.90 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 3.81 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ 164.8, 164.0, 163.3, 158.2, 152.9, 149.6, 147.1, 122.8, 120.7, 112.3, 109.4, 99.1, 56.3, 56.3, 54.0, 53.3. IR (KBr, ν, cm−1): 3014, 1732, 1714, 1620, 1515, 1447, 1275, 1120, 1018, 903. HRMS (ESI): m/z calcd for: C17H16NaO8, 371.0743 [M + Na]+; found: 371.0742.
Dimethyl 6-(4-ethoxyphenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3c). Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.8 Hz, 2H, Ar–H), 6.96 (d, J = 8.8 Hz, 2H, Ar–H), 6.85 (s, 1H, Ar–H), 4.13–4.08 (m, 2H, CH2), 3.94 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 1.47–1.43 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) δ 164.3, 164.0, 163.2, 162.4, 158.7, 145.0, 130.9, 128.8, 128.1, 115.1, 97.8, 63.9, 53.5, 53.1, 14.6. IR (KBr, ν, cm−1): 2978, 1733, 1617, 1540, 1400, 1217, 1130, 1022, 858. HRMS (ESI): m/z calcd for: C17H16O7Na, 355.0794 [M + Na]+; found: 355.0803.
Dimethyl 2-oxo-6-(p-tolyl)-2H-pyran-3,4-dicarboxylate (3d). Yellow solid; mp: 106–108 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.88 (d, J = 8.4 Hz, 2H, Ar–H), 7.39 (d, J = 8.4 Hz, 1H, Ar–H), 7.30 (s, 1H, Ar–H), 3.89 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 2.40 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 164.4, 163.9, 162.8, 158.3, 145.9, 143.1, 130.4, 127.8, 126.6, 117.0, 99.6, 54.0, 53.3, 21.6. IR (KBr, ν, cm−1): 2956, 1749, 1731, 1627, 1510, 1430, 1277, 1133, 1002, 822. HRMS (ESI): m/z calcd for: C16H14O6Na, 325.0688 [M + Na]+; found: 325.0689.
Dimethyl 6-(4-ethylphenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3e). Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H, Ar–H), 7.31 (d, J = 8.4 Hz, 2H, Ar–H), 6.94 (s, 1H, Ar–H), 3.94 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 2.74–2.68 (m, 2H, CH2), 1.26 (t, J = 7.6 Hz, 3H, CH3). 13C NMR (100 MHz, CDCl3) δ 164.1, 164.0, 163.0, 158.7, 149.2, 144.2, 128.7, 127.7, 126.3, 118.2, 98.7, 53.6, 53.2, 28.9, 15.1. IR (KBr, ν, cm−1): 2989, 1752, 1634, 1541, 1400, 1260, 1122, 1037, 874. HRMS (ESI): m/z calcd for: C17H16O6Na, 339.0845 [M + Na]+; found: 339.0854.
Dimethyl 2-oxo-6-phenyl-2H-pyran-3,4-dicarboxylate (3f). Yellow solid, mp: 98–100 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.98 (d, J = 7.6 Hz, 2H, Ar–H), 7.58 (d, J = 7.6 Hz, 3H, Ar–H), 7.35 (s, 1H, Ar–H), 3.90 (s, 3H, OCH3), 3.83 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ 164.2, 163.9, 162.4, 158.3, 145.4, 132.6, 130.5, 129.8, 126.6, 117.9, 100.3, 54.1, 53.4. IR (KBr, ν, cm−1): 2963, 1749, 1714, 1630, 1557, 1455, 1270, 1125, 998, 757. HRMS (ESI): m/z calcd for: C15H12O6Na, 311.0532 [M + Na]+; found: 311.0529.
Dimethyl 6-(4-fluorophenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3g). Yellow solid; mp: 115–117 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.07–8.04 (m, 2H, Ar–H), 7.44–7.40 (m, 2H, Ar–H), 7.34 (s, 1H, Ar–H), 3.90 (s, 3H, OCH3), 3.82 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ 164.7 (1JCF = 249.8 Hz), 164.2, 163.9, 161.5, 158.2, 145.5, 129.4 (3JCF = 9.0 Hz), 127.2 (4JCF = 3.0 Hz), 117.7, 116.9 (2JCF = 22.1 Hz), 100.2, 54.1, 53.4. IR (KBr, ν, cm−1): 2958, 1748, 1728, 1632, 1507, 1417, 1262, 1043, 835, 763. HRMS (ESI): m/z calcd for: C17H16O8Na, 329.0437 [M + Na]+; found: 329.0438.
Dimethyl 6-(4-chlorophenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3h). Yellow solid; mp: 108–110 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.00 (d, J = 8.8 Hz, 2H, Ar–H), 7.64 (d, J = 8.8 Hz, 2H, Ar–H), 7.39 (s, 1H, Ar–H), 3.90 (s, 3H, OCH3), 3.83 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ 164.1, 163.9, 161.1, 158.2, 145.2, 137.3, 129.9, 129.4, 128.4, 100.7, 54.1, 53.4. IR (KBr, ν, cm−1): 2942, 1733, 1717, 1603, 1540, 1427, 1267, 1100, 929, 817. HRMS (ESI): m/z calcd for: C15H11ClO6Na, 345.0142 [M + Na]+; found: 345.0157.
Dimethyl 6-(3,4-dichlorophenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3i). Yellow solid; mp: 114–116 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J = 2.0 Hz, 1H, Ar–H), 7.96–7.94 (m, 1H, Ar–H), 7.96–7.93 (m, 1H, Ar–H), 7.84 (d, J = 8.4 Hz, 1H, Ar–H), 7.51 (s, 1H, Ar–H), 3.90 (s, 3H, OCH3), 3.83 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ 164.0, 163.8, 159.5, 158.2, 144.8, 135.0, 132.7, 131.9, 131.1, 128.4, 126.6, 119.2, 101.6, 54.1, 53.5. IR (KBr, ν, cm−1): 2844, 1738, 1715, 1626, 1538, 1471, 1287, 1127, 817. HRMS (ESI): m/z calcd for: C15H11Cl2O6, 356.9933 [M + H]+; found: 356.9932.
Dimethyl 6-(4-bromophenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3j). Yellow solid; mp: 113–115 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.92 (d, J = 8.8 Hz, 2H, Ar–H), 7.78 (d, J = 8.8 Hz, 2H, Ar–H), 7.40 (s, 1H, Ar–H), 3.90 (s, 3H, OCH3), 3.83 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ 164.1, 163.9, 161.2, 158.2, 145.1, 132.8, 132.2, 130.7, 129.7, 128.5, 126.3, 118.4, 100.7, 54.1, 53.4. IR (KBr, ν, cm−1): 2952, 1744, 1725, 1629, 1551, 1405, 1269, 1117, 925, 848. HRMS (ESI): m/z calcd for: C15H11BrO6Na, 388.9637 [M + Na]+; found: 388.9639.
Dimethyl 2-oxo-6-(4-(trifluoromethyl)phenyl)-2H-pyran-3,4-dicarboxylate (3k). Yellow solid; mp: 186–188 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 8.4 Hz, 2H, Ar–H), 7.94 (d, J = 8.4 Hz, 2H, Ar–H), 7.51 (s, 1H, Ar–H), 3.91 (s, 1H, OCH3), 3.84 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3) δ 163.7, 163.2, 160.2, 158.1, 142.5, 134.8 (JCF = 4.1 Hz), 128.8, 126.4, 126.2 (JCF = 3.7 Hz), 125.6 (JCF = 3.8 Hz), 123.5 (JCF = 270.9 Hz), 100.5 53.8, 53.3, 132.2, 130.7, 129.7, 128.5, 126.3, 118.4, 100.7, 54.1, 53.3. IR (KBr, ν, cm−1): 2977, 1733, 1635, 1558, 1418, 1327, 1208, 1106, 896. HRMS (ESI): m/z calcd for: C16H11F3O6, 379.0405 [M + Na]+; found: 379.0418.
Dimethyl 6-(naphthalen-2-yl)-2-oxo-2H-pyran-3,4-dicarboxylate (3l). Yellow solid; mp: 148–150 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.63 (s, 1H, Ar–H), 8.16 (d, J = 7.2 Hz, 1H, Ar–H), 8.11–8.07 (m, 2H, Ar–H), 8.02 (d, J = 7.6 Hz, 1H, Ar–H), 7.68–7.64 (m, 2H, Ar–H), 7.51 (s, 1H, Ar–H), 3.93 (s, 3H, OCH3), 3.84 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ 164.3, 164.0, 162.4, 158.4, 145.5, 134.7, 133.0, 129.7, 129.5, 128.9, 128.2, 127.7, 127.3, 122.8, 117.8, 100.7, 54.1, 53.4. IR (KBr, ν, cm−1): 2954, 1747, 1714, 1652, 1557, 1436, 1276, 1119, 934, 864. HRMS (ESI): m/z calcd for: C19H14O6Na, 361.0688 [M + Na]+; found: 361.0686.
Diethyl 6-(4-methoxyphenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3m). Yellow solid; mp: 105–107 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.95 (d, J = 9.2 Hz, 2H, Ar–H), 7.22 (s, 1H, Ar–H), 7.12 (d, J = 9.2 Hz, 2H, Ar–H), 4.37–4.31 (m, 2H, CH2), 4.29–4.24 (m, 2H, CH2), 3.87 (s, 3H, OCH3), 1.31 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 167.4, 164.1, 163.5, 162.9, 158.4, 146.3, 132.0, 128.7, 122.8, 115.3, 98.7, 65.5, 63.1, 62.1, 56.1, 30.5, 19.1, 14.0. IR (KBr, ν, cm−1): 2991, 1752, 1728, 1557, 1429, 1267, 1120, 1001, 937, 841. HRMS (ESI): m/z calcd for: C18H19O7, 347.1131 [M + H]+; found: 347.1128.
Diethyl 6-(3,4-dimethoxyphenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3n). Yellow solid; mp: 114–116 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.61–7.59 (m, 1H, Ar–H), 7.47 (d, J = 2.0 Hz, 1H, Ar–H), 7.30 (s, 1H, Ar–H), 7.14 (d, J = 8.8 Hz, 1H, Ar–H), 4.37–4.32 (m, 2H, CH2), 4.30–4.24 (m, 2H, CH2), 3.87 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 1.31 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 164.3, 163.0, 152.9, 149.6, 146.8, 122.8, 120.7, 115.3, 112.3, 109.4, 99.0, 63.1, 62.1, 56.3, 56.3, 14.3, 14.2. IR (KBr, ν, cm−1): 2993, 1760, 1725, 1652, 1531, 1423, 1274, 1147, 1022, 860. HRMS (ESI): m/z calcd for: C19H20O8Na, 399.1056 [M + Na]+; found: 399.1062.
Diethyl 6-(4-ethoxyphenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3o). Yellow solid; mp: 100–102 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J = 8.8 Hz, 2H, Ar–H), 7.20 (s, 1H, Ar–H), 7.10 (d, J = 8.8 Hz, 2H, Ar–H), 4.37–4.31 (m, 2H, CH2), 4.29–4.24 (m, 2H, CH2), 4.17–4.11 (m, 2H, CH2), 1.36 (t, J = 7.2 Hz, 3H, CH3), 1.31 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 164.1, 163.5, 162.9, 162.2, 146.4, 128.7, 122.7, 115.6, 98.7, 64.1, 63.1, 62.1, 15.0, 14.3, 14.2. IR (KBr, ν, cm−1): 2987, 1733, 1716, 1652, 1557, 1399, 1270, 1100, 966, 850. HRMS (ESI): m/z calcd for: C18H18O7Na, 383.1107 [M + Na]+; found: 383.1105.
Diethyl 2-oxo-6-(p-tolyl)-2H-pyran-3,4-dicarboxylate (3p). Yellow solid; mp: 99–101 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.88 (d, J = 8.0 Hz, 2H, Ar–H), 7.39 (d, J = 8.0 Hz, 2H, Ar–H), 7.27 (s, 1H, Ar–H), 4.44–4.32 (m, 2H, CH2), 4.29–4.25 (m, 2H, CH2), 2.40 (s, 3H, CH3), 1.31 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 163.9, 163.4, 162.6, 158.4, 145.6, 143.0, 130.4, 127.8, 126.6, 117.3, 99.6, 63.2, 62.2, 21.6, 14.2, 14.2. IR (KBr, ν, cm−1): 2991, 1752, 1728, 1627, 1511, 1382, 1265, 1122, 1018, 975. HRMS (ESI): m/z calcd for: C18H19O6, 331.1182 [M + H]+; found: 331.1189.
Diethyl 6-(4-ethylphenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3q). Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H, Ar–H), 7.31 (d, J = 8.4 Hz, 2H, Ar–H), 6.95 (s, 1H, Ar–H), 4.43–4.40 (m, 2H, CH2), 4.39–4.37 (m, 2H, CH2), 2.71 (q, J = 7.6 Hz, 2H, CH2), 1.40–1.37 (m, 6H, CH3), 0.96 (t, J = 7.6 Hz, 3H, CH3). 13C NMR (100 MHz, CDCl3) δ 163.7, 163.4, 162.5, 158.9, 149.0, 143.6, 130.9, 128.8, 128.7, 126.2, 118.9, 98.8, 63.0, 62.3, 28.9, 15.2, 14.0, 13.9. IR (KBr, ν, cm−1): 2936, 1734, 1618, 1508, 1419, 1258, 1113, 1073, 831. HRMS (ESI): m/z calcd for: C19H20O6Na, 367.1158 [M + Na]+; found: 367.1172.
Diethyl 2-oxo-6-phenyl-2H-pyran-3,4-dicarboxylate (3r). Yellow solid; mp: 98–100 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.99–7.96 (m, 2H, Ar–H), 7.59 (t, J = 7.2 Hz, 3H, Ar–H), 7.32 (s, 1H, Ar–H), 4.38–4.33 (m, 2H, CH2), 4.32–4.26 (m, 2H, CH2), 1.33 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 163.7, 163.4, 162.2, 158.4, 145.2, 132.5, 130.5, 129.8, 126.6, 118.1, 100.2, 63.2, 62.3, 14.2, 14.2. IR (KBr, ν, cm−1): 2990, 1750, 1723, 1627, 1497, 1386, 1272, 1062, 977, 872. HRMS (ESI): m/z calcd for: C17H16O6Na, 339.0845 [M + Na]+; found: 339.0851.
Diethyl 6-(4-fluorophenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3s). Yellow solid; mp: 103–105 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.07–8.03 (m, 2H, Ar–H), 7.42 (t, J = 8.8 Hz, 2H), 7.32 (s, 1H, Ar–H), 4.38–4.32 (m, 2H, CH2), 4.31–4.26 (m, 2H, CH2), 1.32 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 163.7, 164.6 (1JCF = 249.8 Hz), 163.4, 163.3, 158.3, 145.3, 129.4 (3JCF = 9.1 Hz), 127.2 (4JCF = 3.0 Hz), 118.0, 116.9 (2JCF = 22.1 Hz), 100.2, 63.2, 62.3, 14.2, 14.2. IR (KBr, ν, cm−1): 2934, 1747, 1724, 1627, 1553, 1374, 1241, 1113, 1024, 971. HRMS (ESI): m/z calcd for: C19H20O8Na, 357.0750 [M + Na]+; found: 357.0776.
Diethyl 6-(4-chlorophenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3t). Yellow solid; mp: 92–94 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.01–7.99 (m, 2H, Ar–H), 7.66–7.65 (m, 2H, Ar–H), 7.40 (s, 1H, Ar–H), 4.38–4.32 (m, 2H, CH2), 4.32–4.26 (m, 2H, CH2), 1.32 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 163.6, 163.3, 160.9, 158.3, 145.0, 137.2, 129.8, 129.4, 128.4, 118.6, 100.7, 63.3, 62.3, 14.2, 14.2. IR (KBr, ν, cm−1): 2963, 1747, 1732, 1661, 1558, 1399, 1270, 1096, 1012, 832. HRMS (ESI): m/z calcd for: C17H16ClO6, 351.0635 [M + H]+; found: 351.0636.
Diethyl 6-(4-bromophenyl)-2-oxo-2H-pyran-3,4-dicarboxylate (3u). Yellow solid; mp: 93–95 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.92 (d, J = 8.0 Hz, 2H, Ar–H), 7.78 (d, J = 8.4 Hz, 2H, Ar–H), 3.37 (s, 1H, Ar–H), 4.37–4.32 (m, 2H, CH2), 4.31–4.26 (m, 2H, CH2), 1.32 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 163.6, 163.3, 161.0, 158.3, 144.9, 132.8, 129.8, 128.5, 126.2, 118.7, 100.7, 63.3, 62.3, 14.2, 14.2. IR (KBr, ν, cm−1): 2987, 1745, 1719, 1625, 1508, 1375, 1268, 1116, 1006, 828. HRMS (ESI): m/z calcd for: C17H16BrO6, 395.0130 [M + H]+; found: 395.0156.
Diethyl 6-(naphthalen-2-yl)-2-oxo-2H-pyran-3,4-dicarboxylate (3v). Yellow solid; mp: 136–138 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 1H, Ar–H), 8.17–8.15 (m, 1H, Ar–H), 8.11–8.07 (m, 2H, Ar–H), 8.05–8.01 (m, 1H, Ar–H), 7.69–7.62 (m, 2H, Ar–H), 7.48 (s, 1H, Ar–H), 4.40–4.35 (m, 2H, CH2), 4.33–4.28 (m, 2H, CH2), 1.34 (t, J = 7.2 Hz, 3H, CH3), 1.29 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 163.8, 163.4, 162.2, 158.5, 145.3, 134.7, 133.0, 129.7, 129.5, 128.9, 128.2, 127.8, 127.7, 127.2, 122.8, 118.0, 100.7, 63.3, 62.3, 14.3, 14.2. IR (KBr, ν, cm−1): 2987, 1749, 1734, 1636, 1507, 1398, 1259, 1043, 958, 818. HRMS (ESI): m/z calcd for: C21H18O6Na, 389.1001 [M + Na]+; found: 389.0978.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We are grateful for financial support from the NSFC (No. 21232004, 21472071, and 21602087), the PAPD of Jiangsu Higher Education Institutions, the Outstanding Youth Fund of JSNU (YQ2015003), the NSF of Jiangsu Province (BK20151163 and BK20160212), the Qing Lan Project and the NSF of Jiangsu Education Committee (15KJB150006).

Notes and references

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Footnotes

Electronic supplementary information (ESI) available. CCDC 1575314 (3a). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7qo00899f
These authors contributed equally.

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