2016 Volume 64 Issue 12 Pages 1763-1768
An efficient and practical synthesis of 2′,3′-nonsubstituted cyclohexane-1,3-dione-2-spirocyclopropanes using a sulfonium salt was achieved. The reaction of 1,3-cyclohexanediones and (2-bromoethyl)diphenylsulfonium trifluoromethanesulfonate with powdered K2CO3 in EtOAc at room temperature (r.t.) provided the corresponding spirocyclopropanes in high yields. The synthetic method was also applied to 1,3-cyclopentanedione, 1,3-cycloheptanedione, 1,3-indanedione, acyclic 1,3-diones, ethyl acetoacetate, and Meldrum’s acid.
Cyclopropanes are extremely versatile building blocks in organic synthesis because of the high reactivity arising from their strong ring strain.1,2) Ring-opening cyclization of doubly activated cyclopropanes has emerged as a powerful method for the synthesis of a variety of carbo- and heterocyclic compounds.3–6) Recently, we demonstrated the formation of indole skeletons by employing the ring-opening cyclization of the doubly activated spirocyclopropanes, 2′-arylcyclohexane-1,3-dione-2-spirocyclopropanes 1, with primary amines7) (Chart 1). The reaction proceeded regioselectively at room temperature (r.t.) to give 2-aryltetrahydroindol-4-ones 2, one of which was easily converted to the 4-hydroxyindole derivative 3. We also reported acid-catalyzed ring-opening cyclization of spirocyclopropanes 1 to 2-aryltetrahydro-1-benzofuran-4-ones 4 and its application to the synthesis of 4-hydroxybenzofuran 5.8) In order to achieve syntheses of indole and benzofuran natural products and also to further our understanding of the reaction mechanisms, we need to investigate the ring-opening cyclization of 2′,3′-nonsubstituted cyclohexane-1,3-dione-2-spirocyclopropanes. However, very few methods for their synthesis have been reported.9,10) These circumstances have led us to develop a novel, efficient, and practical method for preparing 2′,3′-nonsubstituted spirocyclopropanes. Herein, we report the synthetic method for 2′,3′-nonsubstituted cyclohexane-1,3-dione-2-spirocyclopropanes using 2-bromoethylsulfonium salt.
Rh(II)-catalyzed cyclopropanation of alkenes with diazo compounds is widely employed for the synthesis of a variety of doubly activated cyclopropanes, but it is not suitable for application to spiro systems.11) Furthermore, it requires an unpractical ethene gas.12)
2,3-Nonsubstituted 1,1-diacylcyclopropanes can be prepared from 1,3-dicarbonyl compounds by double alkylation using 1,2-dibromoethane. For example, the reaction of acetylacetone (6a) and 1,2-dibromoethane with potassium carbonate in dimethyl sulfoxide (DMSO) afforded the corresponding cyclopropane 7a in 61% yield13) (Chart 2). The conversion of 1-phenyl-1,3-butanedione (6b) into cyclopropane 7b was also conducted in the same manner.14) Therefore, we initially examined the reaction of 1,3-cyclohexanedione (8a) and 1,2-dibromoethane under the same reaction conditions (Chart 3). However, 2′,3′-nonsubstituted spirocyclopropane 1a was not detected; instead, O-alkylation product 915) was obtained in 36% yield.
As an alternative double alkylation approach, the synthetic method using a sulfonium salt in place of 1,2-dibromoethane has been developed. In 2012, Lin and colleagues reported a simple and efficient access to 1,1-cyclopropane aminoketones 12 via the reaction of α-aminoacetophenones 10 and vinylsulfonium salt 11 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)16) (Chart 4). The vinylsulfonium salt 11 was prepared from (2-bromoethyl)diphenylsulfonium trifluoromethanesulfonate (13)17–21) by eliminating the hydrogen bromide with a base such as silver(I) oxide,17,18) potassium bicarbonate,19,22) or sodium hydride (NaH).20) Recently, we developed a simple preparation of 2′-arylcyclohexane-1,3-dione-2-spirocyclopropanes 1 from 1,3-cyclohexanediones 8 directly using (1-aryl-2-bromoethyl)dimethylsulfonium bromides 14, which were converted into the corresponding vinylsulfonium salt in situ23) (Chart 5). Therefore, we envisioned that the reaction of 1,3-cyclohexanediones 8 using 13 with an appropriate base would provide 2′,3′-nonsubstituted spirocyclopropanes.
The sulfonium salt 13 was prepared using a slightly modified procedure, originally reported by Aggarwal and colleagues22) (Chart 6). The conversion of 2-bromoethanol (15) into triflate 16 with trifluoromethanesulfonic anhydride and pyridine in CH2Cl2 followed by treatment with diphenyl sulfide in toluene at reflux afforded the sulfonium salt 13 in 70% overall yield. First, we investigated the reaction of 8a with 1.5 eq of 13 using 3 eq of DBU in CH2Cl2 at r.t. The reaction did not complete even after 24 h, and gave the corresponding spirocyclopropane 1a in only 19% yield (Table 1, entry 1). When NaH was used in CH2Cl2, the reaction for 15 h afforded 1a in 72% yield (entry 2). Changing the base to KHCO3 resulted in a similar reaction rate (17 h) and increased the product yield to 84% (entry 3). Next, we investigated powdered potassium carbonate as a base23) (Chart 5). Remarkably, the use of powdered K2CO3 enhanced the reaction rate (1.5 h) and afforded 1a in 84% yield (entry 4). Switching the solvent from CH2Cl2 to N,N-dimethylformamide (DMF) improved the reaction rate (1 h), although a considerable decrease in the product yield was observed (72% yield, entry 5). Delightfully, the reaction in EtOAc for 1.5 h gave 1a in 87% yield (entry 6). The use of granular K2CO3 slightly decreased the product yield (83% yield) and gave irreproducible conversion (entry 7). We next optimized the amount of sulfonium salt 13. Using 1.2 eq of 13 led to a slight drop in the product yield (84% yield, entry 8), and the use of 2.0 eq of 13 appreciably diminished the product yield (81% yield, entry 9). Thus, we achieved the direct synthesis of spirocyclopropane 1a from 8a using 1.5 eq of sulfonium salt 13 and 3 eq of powdered K2CO3 in EtOAc.
 | ||||
|---|---|---|---|---|
| Entry | Base | Solvent | Time (h) | Yield (%) |
| 1 | DBU | CH2Cl2 | 24 | 19b) |
| 2 | NaH | CH2Cl2 | 15 | 72 |
| 3 | Powdered KHCO3 | CH2Cl2 | 17 | 84 |
| 4 | Powdered K2CO3 | CH2Cl2 | 1.5 | 84 |
| 5 | Powdered K2CO3 | DMF | 1 | 72 |
| 6 | Powdered K2CO3 | EtOAc | 1.5 | 87 |
| 7 | Granular K2CO3 | EtOAc | 1.5 | 83c) |
| 8d) | Powdered K2CO3 | EtOAc | 1.5 | 84 |
| 9e) | Powdered K2CO3 | EtOAc | 1.5 | 81 |
a) All reactions were performed on a 0.5 mmol scale with 1.5 eq of sulfonium salt 13 and 3 eq of base. b) The starting material 8a was recovered in 30% yield. c) Irreproducible yield. d) 1.2 eq of sulfonium salt 13 and 2.4 eq of powdered K2CO3 were used. e) 2.0 eq of sulfonium salt 13 and 4.0 eq of powdered K2CO3 were used.
With the optimal conditions in hand, we investigated the reaction with a variety of 1,3-cyclohexanediones 8b–h with 1.5 eq of sulfonium salt 13 (Table 2). High yields of spirocyclopropanes 1b–h (80–88% yields) were consistently obtained in the reactions of dimedone (8b), 5-methyl-, 5-isopropyl- and 5-phenylcyclohexane-1,3-diones (8c–e), spiro[2.5]octane-5,7-dione (8f), and 4,4-dimethyl- and 4-methylcyclohexane-1,3-dione (8g, h) (entries 1–7). We next turned our attention to the reaction of 5- and 7-membered carbocycles with 13. The reaction of 1,3-cyclopentanedione (17) and 1,3-cycloheptanedione (19) afforded the corresponding spirocyclopropanes 18 and 20 in 77 and 71% yields, respectively (entries 8, 9). The present protocol was found to be applicable to 1,3-indanedione (21), affording the corresponding spirocyclopropane 2224) in 86% yield (entry 10).
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a) All reactions were performed on a 0.5 mmol scale with 1.5 eq of sulfonium salt 13 and 3 eq of powdered K2CO3 in EtOAc.
In addition, the synthesis of acyclic 1,3-dione-derived cyclopropanes using the present protocol was examined (Chart 7). The reaction of acetylacetone (6a) with 1.5 equiv of sulfonium salt 13 using powdered K2CO3 in EtOAc provided the corresponding cyclopropane 7a in 79% yield. The use of 1-phenyl-1,3-butanedione (6b) afforded cyclopropane 7b in 83% yield. Since the yields of 7a, b were higher than those in Chart 2,13,14) these results clearly demonstrate that the present synthetic method using the sulfonium salt 13 is also effective for the synthesis of acyclic 1,3-dione-derived cyclopropanes.
Finally, we investigated the synthesis of cyclopropanecarboxylates (Chart 8). The reaction of ethyl acetoacetate (23) with sulfonium salt 13 and powdered K2CO3 in EtOAc for 1.5 h gave ethyl 1-acetylcyclopropanecarboxylate (24) in only 71% yield. On the other hand, the reaction of dimethyl malonate (25) with 13 for 4 h gave dimethyl 1,1-cyclopropanedicarboxylate (26) in only 49% yield, and some decomposition products.25) Interestingly, the use of Meldrum’s acid (27) afforded the corresponding spirocyclopropane 28 in 80% yield. We speculate that the higher acidity of Meldrum’s acid (27: pKa 7.3, in DMSO at 25°C)26) than that of dimethyl malonate (25: pKa 15.9, in DMSO at 25°C) is the reason for the success of the reaction.
In summary, we have developed an efficient procedure for the synthesis of 2′,3′-nonsubstituted cyclohexane-1,3-dione-2-spirocyclopropanes. The reaction of 1,3-cyclohexanediones and (2-bromoethyl)diphenylsulfonium trifluoromethanesulfonate with powdered K2CO3 in EtOAc at r.t. provided the corresponding spirocyclopropanes in high yields. The present protocol was also found to be applicable to 1,3-cyclopentanedione, 1,3-cycloheptanedione, 1,3-indanedione, acyclic 1,3-diones, ethyl acetoacetate, and Meldrum’s acid.
Melting points are uncorrected. IR spectra were recorded on a JASCO FT/IR-460 Plus spectrophotometer and absorbance bands are reported in wavenumber (cm−1). All NMR spectra were recorded using a JEOL JNM-ECX400P spectrometer. 1H-NMR spectra were recorded at 400 MHz. Chemical shifts are reported relative to internal standard (tetramethylsilane at δH 0.00 or CDCl3 at δH 7.26). Data are presented as follows: chemical shift (δ, ppm), multiplicity (s=singlet, d=doublet, t=triplet, quint=quintet, m=multiplet), coupling constant and integration. 13C-NMR spectra were recorded at 100 MHz. The following internal reference was used (CDCl3 at δC 77.0). All 13C-NMR spectra were determined with complete proton decoupling. High-resolution (HR) mass spectra were determined with JEOL JMS-GCmate II instrument. Column chromatography was performed on Silica Gel 60 PF254 (Nacalai Tesque, Inc., Kyoto, Japan) and Kanto silica gel 60 N (63–210 mesh) under pressure. Analytical TLC was carried out on Merck Kieselgel 60 F254 plates. Visualization was accomplished with UV light and phosphomolybdic acid stain solution followed by heating.
All reagents such as 1,3-cyclohexanedione (8a) and its derivatives 8b, c, e, and g, 1,3-cyclopentanedione (17), 1,3-cycloheptanedione (19), 1,3-indanedione (21), acetylacetone (6a), 1-phenyl-1,3-dutanedione (6b), ethyl acetoacetate (23), dimethyl malonate (25), Meldrum’s acid (27), and powdered K2CO3 are commercially available and were purchased from suppliers such as Sigma-Aldrich Co., U.S.A., Tokyo Chemical Industry Co., Ltd., Tokyo, Japan, Wako Pure Chemical Industries, Ltd., Osaka, Japan and Nacalai Tesque, Inc. Dehydrated DMSO CH2Cl2, toluene, DMF, and EtOAc were purchased from Wako Pure Chemical Industries, Ltd. 5-Isopropylcyclohexane-1,3-dione (8d),27) spiro[2.5]octane-5,7-dione (8f),28) and 4-methylcyclohexane-1,3-dione (8h)29) were prepared according to literature procedures.
Preparation of (2-Bromoethyl)diphenylsulfonium Trifluoromethanesulfonate (13) from 2-Bromoethanol (15) (Chart 6)A solution of triflic anhydride (1.81 mL, 11 mmol) in CH2Cl2 (5 mL) was added to a solution of pyridine (0.88 mL, 11 mmol) in CH2Cl2 (5 mL) at −20°C. After stirring for 10 min, 2-bromoethanol (15) (0.71 mL, 10 mmol) was added to the mixture and the reaction mixture was stirred at −20°C for 15 min. The precipitate was removed by filtration and washed with Et2O (10 mL). The combined filtrates were concentrated in vacuo, and the residue was diluted with hexane (30 mL). The precipitate was removed by filtration and washed with Et2O (5 mL). The combined filtrates were concentrated in vacuo to provide crude product 16 (2.38 g), which was used in the next step without further purification.
Diphenyl sulfide (6.90 g, 18.5 mmol) was added to a solution of crude product 16 in toluene (9 mL) at r.t. The reaction mixture was then heated at 100°C and stirred for 7 h. The solution was allowed to cool to r.t. and Et2O (20 mL) was added, resulting in the formation of a white precipitate. The mixture was stirred at r.t. overnight and the precipitate was collected by suction, washed with Et2O (3 mL) and dried in vacuo to provide 13 (3.10 g, 70%) as a white solid: mp 85.0–86.0°C (lit.,17) mp 86.5–88.0°C); IR (KBr, cm−1) ν 3065, 2986, 1448, 1274, 1149, 1032, 755, 638; 1H-NMR (400 MHz, CDCl3) δ: 8.13–8.09 (m, 4H), 7.81–7.70 (m, 6H), 4.93–4.87 (m, 2H), 3.71–3.67 (m, 2H); 13C-NMR (100 MHz, CDCl3) δ: 135.3, 131.9, 131.1, 122.7, 48.5, 24.0.
Typical Procedure for the Synthesis of Spirocyclopropanes 1: Spiro[2.5]octane-4,8-dione (1a) (Table 1, Entry 6)Powdered K2CO3 (207 mg, 1.5 mmol) and 1,3-cyclohexanedione (8a) (56 mg, 0.50 mmol) were added to a suspension of sulfonium salt 13 (332 mg, 0.75 mmol) in EtOAc (5 mL). After stirring at r.t. for 1.5 h, the reaction was quenched with water (10 mL) and the whole mixture was extracted with EtOAc (2×10 mL). The combined organic layer was washed with brine (10 mL) and dried over anhydrous MgSO4. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (silica gel, 30% EtOAc in hexane) to provide 1a (60 mg, 87%) as a colorless oil; IR (film, cm−1) ν 2956, 1682, 1330, 1162, 1026, 956; 1H-NMR (400 MHz, CDCl3) δ: 2.67 (t, J=6.4 Hz, 4H), 2.14 (quint, J=6.4 Hz, 2H), 1.77 (s, 4H); 13C-NMR (100 MHz, CDCl3) δ: 206.9, 40.8, 39.5, 27.6, 18.0; HR-MS electron ionization (EI) m/z Calcd for C8H10O2 (M+) 138.0681. Found 138.0668.
6,6-Dimethylspiro[2.5]octane-4,8-dione (1b)9) (Table 2, Entry 1)According to the typical procedure for the synthesis of 1a, 1b was prepared from dimedone (8b) (70 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 30% EtOAc in hexane) to provide 1b (73 mg, 88%) as a colorless oil: IR (film, cm−1) ν 2957, 2871, 1710, 1683, 1469, 1404, 1371, 1335, 1320, 1291, 1181, 1145, 1123, 1082, 987, 918; 1H-NMR (400 MHz, CDCl3) δ: 2.56 (s, 4H), 1.76 (s, 4H), 1.13 (s, 6H); 13C-NMR (100 MHz, CDCl3) δ: 206.8, 53.2, 39.6, 30.3, 28.5, 27.3.
6-Methylspiro[2.5]octane-4,8-dione (1c) (Table 2, Entry 2)According to the typical procedure for the synthesis of 1a, 1c was prepared from 5-methylcyclohexane-1,3-dione (8c) (63 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 40% EtOAc in hexane) to provide 1c (64 mg, 84%) as a colorless oil: IR (film, cm−1) ν 2958, 1683, 1321, 1165, 950; 1H-NMR (400 MHz, CDCl3) δ: 2.80–2.71 (m, 2H), 2.44–2.34 (m, 3H), 1.76 (s, 4H), 1.15 (d, J=6.0 Hz, 3H); 13C-NMR (100 MHz, CDCl3) δ: 206.7, 47.5, 40.1, 27.7, 27.4, 25.4, 21.0; HR-MS (EI) m/z Calcd for C9H12O2 (M+) 152.0837. Found 152.0835.
6-Isopropylspiro[2.5]octane-4,8-dione (1d) (Table 2, Entry 3)According to the typical procedure for the synthesis of 1a, 1d was prepared from 5-isopropylcyclohexane-1,3-dione (8d)27) (77 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 20% EtOAc in hexane) to provide 1d (78 mg, 87%) as a colorless oil; IR (film, cm−1) ν 2962, 2879, 1683, 1332, 1160, 1082; 1H-NMR (400 MHz, CDCl3) δ: 2.75 (dd, J=16.5, 3.2 Hz, 2H), 2.43 (dd, J=16.5, 11.9 Hz, 2H), 2.05 (m, 1H), 1.75 (s, 4H), 1.68 (m, 1H), 0.97 (d, J=6.4 Hz, 6H); 13C-NMR (100 MHz, CDCl3) δ: 207.1, 43.5, 40.1, 36.2, 31.5, 27.7, 27.4, 19.2; HR-MS (EI) m/z Calcd for C11H16O2 (M+) 180.1150. Found 180.1154.
6-Phenylspiro[2.5]octane-4,8-dione (1e) (Table 2, Entry 4)According to the typical procedure for the synthesis of 1a, 1e was prepared from 5-phenylcyclohexane-1,3-dione (8e) (94 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 30% EtOAc in hexane) to provide 1e (91 mg, 85%) as a white solid: mp 117.0–118.0°C; IR (KBr, cm−1) ν 1675, 1333, 1163, 768, 703; 1H-NMR (400 MHz, CDCl3) δ: 7.37 (t, J=7.3 Hz, 2H), 7.29 (d, J=7.3 Hz, 1H), 7.24 (d, J=7.3 Hz, 2H), 3.54 (tt, J=11.4, 4.1 Hz, 1H), 2.99 (dd, J=16.9, 4.1 Hz, 2H), 2.87 (dd, J=16.9, 11.4 Hz, 2H), 1.89–1.77 (m, 4H); 13C-NMR (100 MHz, CDCl3) δ: 206.0, 141.8, 129.0, 127.3, 126.5, 46.9, 40.4, 35.7, 28.1; HR-MS (EI) m/z Calcd for C14H14O2 (M+) 214.0994. Found 214.0967.
Dispiro[2.2.2.2]decane-4,10-dione (1f) (Table 2, Entry 5)According to the typical procedure for the synthesis of 1a, 1f was prepared from spiro[2.5]octane-5,7-dione (8f)28) (69 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 30% EtOAc in hexane) to provide 1f (72 mg, 88%) as a white solid: mp 30.5–32.0°C; IR (KBr, cm−1) ν 2362, 1685, 1320, 1136, 1084; 1H-NMR (400 MHz, CDCl3) δ: 2.54 (s, 4H), 1.79 (s, 4H), 0.54 (s, 4H); 13C-NMR (100 MHz, CDCl3) δ: 206.1, 48.5, 40.6, 27.4, 12.5, 10.5; HR-MS (EI) m/z Calcd for C10H12O2 (M+) 164.0837. Found 164.0860.
5,5-Dimethylspiro[2.5]octane-4,8-dione (1g) (Table 2, Entry 6)According to the typical procedure for the synthesis of 1a, 1g was prepared from 4,4-dimethylcyclohexane-1,3-dione (8g) (70 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 20% EtOAc in hexane) to provide 1g (67 mg, 81%) as a colorless oil; IR (film, cm−1) ν 2966, 2361, 1684, 1329, 1058; 1H-NMR (400 MHz, CDCl3) δ: 2.69 (t, J=6.9 Hz, 2H), 1.98 (t, J=6.9 Hz, 2H), 1.75–1.69 (m, 4H), 1.22 (s, 6H); 13C-NMR (100 MHz, CDCl3) δ: 210.8, 207.3, 43.0, 38.9, 35.5, 31.8, 27.3, 24.6; HR-MS (EI) m/z Calcd for C10H14O2 (M+) 166.0994. Found 166.0972.
5-Methylspiro[2.5]octane-4,8-dione (1h) (Table 2, Entry 7)According to the typical procedure for the synthesis of 1a, 1h was prepared from 4-methylcyclohexane-1,3-dione (8h)29) (63 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 20% EtOAc in hexane) to provide 1h (61 mg, 80%) as a colorless oil; IR (film, cm−1) ν 2362, 1683, 1331, 756; 1H-NMR (400 MHz, CDCl3) δ: 2.78 (dt, J=18.3, 4.1 Hz, 1H), 2.68–2.54 (m, 2H), 2.20 (m, 1H), 1.93–1.65 (m, 5H), 1.24 (d, J=6.9 Hz, 3H); 13C-NMR (100 MHz, CDCl3) δ: 208.4, 207.3, 43.6, 40.1, 38.9, 27.8, 26.9, 26.2, 15.3; HR-MS (EI) m/z Calcd for C9H12O2 (M+) 152.0837. Found 152.0832.
Spiro[2.4]heptane-4,7-dione (18) (Table 2, Entry 8)According to the typical procedure for the synthesis of 1a, 18 was prepared from 1,3-cyclopentanedione (17) (49 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 60% EtOAc in hexane) to provide 18 (48 mg, 77%) as a white solid: mp 135.0–136.0°C; IR (KBr, cm−1) ν 3099, 1701, 1427, 1343, 1130, 1115, 924; 1H-NMR (400 MHz, CDCl3) δ: 2.85 (s, 4H), 1.79 (s, 4H); 13C-NMR (100 MHz, CDCl3) δ: 212.6, 38.9, 35.5, 26.7; HR-MS (EI) m/z Calcd for C7H8O2 (M+) 124.0524. Found 124.0488.
Spiro[2.6]nonane-4,9-dione (20) (Table 2, Entry 9)According to the typical procedure for the synthesis of 1a, 20 was prepared from 1,3-cycloheptanedione (19) (63 mg, 0.50 mmol) for 2 h. The crude product was purified by column chromatography (silica gel, 20% EtOAc in hexane) to provide 20 (54 mg, 71%) as a colorless oil: IR (film, cm−1) ν 2937, 1680, 1454, 1330, 1298, 1110; 1H-NMR (400 MHz, CDCl3) δ: 2.74–2.71 (m, 4H), 2.01–1.97 (m, 4H), 1.49 (s, 4H); 13C-NMR (100 MHz, CDCl3) δ: 207.5, 43.2, 41.7, 23.1, 21.7; HR-MS (EI) m/z Calcd for C9H12O2 (M+) 152.0837. Found 152.0852.
Spiro[cyclopropane-1,2′-(2H)-indene]-1′,3′-dione (22)24) (Table 2, Entry 10)According to the typical procedure for the synthesis of 1a, 22 was prepared from 1,3-indanedione (21) (73 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 40% EtOAc in hexane) to provide 22 (74 mg, 86%) as a white solid: mp 94.0–95.0°C; IR (KBr, cm−1) ν 3047, 1712, 1600, 1361, 1204, 1069, 788; 1H-NMR (400 MHz, CDCl3) δ: 7.97 (dd, J=5.6, 3.2 Hz, 2H), 7.82 (dd, J=5.6, 3.2 Hz, 2H), 1.78 (s, 4H); 13C-NMR (100 MHz, CDCl3) δ: 199.2, 142.1, 134.8, 122.5, 35.7, 20.4.
1,1-Diacetylcyclopropane (7a) (Chart 7)According to the typical procedure for the synthesis of 1a, 7a was prepared from acetylacetone (6a) (49 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 40% EtOAc in hexane) to provide 7a (50 mg, 79%) as a colorless oil; IR (film, cm−1) ν 2368, 2330, 1689, 1365, 761; 1H-NMR (400 MHz, CDCl3) δ: 2.23 (s, 6H), 1.48 (s, 4H); 13C-NMR (100 MHz, CDCl3) δ: 203.9, 43.2, 27.7, 17.4.
1-Acetyl-1-benzoylcyclopropane (7b) (Chart 7)According to the typical procedure for the synthesis of 1a, 7b was prepared from 1-phenyl-1,3-butanedione (6b) (81 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 20% EtOAc in hexane) to provide 7b (78 mg, 83%) as a colorless oil; IR (film, cm−1) ν 2368, 2335, 1672, 1324, 1135, 1006; 1H-NMR (400 MHz, CDCl3) δ: 7.93 (d, J=7.3 Hz, 2H), 7.59 (t, J=7.3 Hz, 1H), 7.48 (t, J=7.3 Hz, 2H), 2.06 (s, 3H), 1.62–1.59 (m, 2H), 1.52–1.49 (m, 2H); 13C-NMR (100 MHz, CDCl3) δ: 203.9, 196.4, 136.7, 133.5, 128.9, 128.8, 41.9, 29.2, 17.1.
Ethyl 1-Acetylcyclopropanecarboxylate (24) (Chart 8)According to the typical procedure for the synthesis of 1a, 24 was prepared from ethyl acetoacetate (23) (65 mg, 0.50 mmol) for 1.5 h. The crude product was purified by column chromatography (silica gel, 10% EtOAc in hexane) to provide 24 (55 mg, 71%) as a colorless oil; IR (film, cm−1) ν 2931, 2860, 2360, 1734, 1714, 1542, 1457, 755; 1H-NMR (400 MHz, CDCl3) δ: 4.21 (q, J=3.4 Hz, 2H), 2.47 (s, 3H), 1.47 (s, 4H), 1.29 (t, J=3.4 Hz, 3H); 13C-NMR (100 MHz, CDCl3) δ: 203.1, 171.0, 61.2, 35.1, 29.8, 19.1, 14.1.
Dimethyl 1,1-Cyclopropanedicarboxylate (26) (Chart 8)According to the typical procedure for the synthesis of 1a, 26 was prepared from dimethyl malonate (25) (66 mg, 0.50 mmol) for 4 h. The crude product was purified by column chromatography (silica gel, 10% EtOAc in hexane) to provide 26 (39 mg, 49%) as a colorless oil; IR (film, cm−1) ν 3227, 1732, 1443, 1322, 1218, 1136, 755; 1H-NMR (400 MHz, CDCl3) δ: 3.75 (s, 6H), 1.47 (s, 4H); 13C-NMR (100 MHz, CDCl3) δ: 170.2, 52.6, 27.8, 16.7.
6,6-Dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (28) (Chart 8)According to the typical procedure for the synthesis of 1a, 28 was prepared from Meldrum’s acid (27) (72 mg, 0.50 mmol) for 2 h. The crude product was purified by column chromatography (silica gel, 30% EtOAc in hexane) to provide 28 (68 mg, 80%) as a white solid, which was directly identical to the commercial sample supplied by Tokyo Chemical Industry Co., Ltd. mp 60.5–61.5°C; IR (KBr, cm−1) ν 2368, 1775, 1742, 1400, 1340, 1200, 1047, 970 856, 730; 1H-NMR (400 MHz, CDCl3) δ: 1.99 (s, 4H), 1.82 (s, 6H); 13C-NMR (100 MHz, CDCl3) δ: 168.1, 105.1, 27.6, 24.1, 23.9.
This research was supported, in part, by a Grant-in-Aid for Scientific Research (C) (Grant No. JP15K07853) from the Japan Society for the Promotion of Science (JSPS).
The authors declare no conflict of interest.
