1766
Chem. Pharm. Bull.
Vol. 64, No. 12 (2016)
cloheptanedione (19), 1,3-indanedione (21), acetylacetone provide 1b (73mg, 88%) as a colorless oil: IR (film, cm−1) ν
(6a), 1-phenyl-1,3-dutanedione (6b), ethyl acetoacetate (23), 2957, 2871, 1710, 1683, 1469, 1404, 1371, 1335, 1320, 1291,
1
dimethyl malonate (25), Meldrum’s acid (27), and powdered 1181, 1145, 1123, 1082, 987, 918; H-NMR (400MHz, CDCl3)
K2CO3 are commercially available and were purchased from δ: 2.56 (s, 4H), 1.76 (s, 4H), 1.13 (s, 6H); 13C-NMR (100MHz,
suppliers such as Sigma-Aldrich Co., U.S.A., Tokyo Chemical CDCl3) δ: 206.8, 53.2, 39.6, 30.3, 28.5, 27.3.
Industry Co., Ltd., Tokyo, Japan, Wako Pure Chemical Indus-
6-Methylspiro[2.5]octane-4,8-dione (1c) (Table 2, Entry
tries, Ltd., Osaka, Japan and Nacalai Tesque, Inc. Dehydrated 2) According to the typical procedure for the synthesis of
DMSO CH2Cl2, toluene, DMF, and EtOAc were purchased 1a, 1c was prepared from 5-methylcyclohexane-1,3-dione (8c)
from Wako Pure Chemical Industries, Ltd. 5-Isopropylcyclo- (63mg, 0.50mmol) for 1.5h. The crude product was purified
hexane-1,3-dione (8d),27) spiro[2.5]octane-5,7-dione (8f),28) and by column chromatography (silica gel, 40% EtOAc in hexane)
4-methylcyclohexane-1,3-dione (8h)29) were prepared accord- to provide 1c (64mg, 84%) as a colorless oil: IR (film, cm−1)
1
ing to literature procedures.
ν 2958, 1683, 1321, 1165, 950; H-NMR (400MHz, CDCl3) δ:
Preparation of (2-Bromoethyl)diphenylsulfonium Triflu- 2.80–2.71 (m, 2H), 2.44–2.34 (m, 3H), 1.76 (s, 4H), 1.15 (d,
oromethanesulfonate (13) from 2-Bromoethanol (15) (Chart J=6.0Hz, 3H); 13C-NMR (100MHz, CDCl3) δ: 206.7, 47.5,
6) A solution of triflic anhydride (1.81mL, 11mmol) in 40.1, 27.7, 27.4, 25.4, 21.0; HR-MS (EI) m/z Calcd for C9H12O2
CH2Cl2 (5mL) was added to a solution of pyridine (0.88mL, (M+) 152.0837. Found 152.0835.
11mmol) in CH2Cl2 (5mL) at −20°C. After stirring for
6-Isopropylspiro[2.5]octane-4,8-dione (1d) (Table 2, Entry
10min, 2-bromoethanol (15) (0.71mL, 10mmol) was added to 3) According to the typical procedure for the synthesis of
the mixture and the reaction mixture was stirred at −20°C for 1a, 1d was prepared from 5-isopropylcyclohexane-1,3-dione
15min. The precipitate was removed by filtration and washed (8d)27) (77mg, 0.50mmol) for 1.5h. The crude product was
with Et2O (10mL). The combined filtrates were concentrated purified by column chromatography (silica gel, 20% EtOAc
in vacuo, and the residue was diluted with hexane (30mL). in hexane) to provide 1d (78mg, 87%) as a colorless oil; IR
1
The precipitate was removed by filtration and washed with (film, cm−1) ν 2962, 2879, 1683, 1332, 1160, 1082; H-NMR
Et2O (5mL). The combined filtrates were concentrated in (400MHz, CDCl3) δ: 2.75 (dd, J=16.5, 3.2Hz, 2H), 2.43 (dd,
vacuo to provide crude product 16 (2.38g), which was used in J=16.5, 11.9Hz, 2H), 2.05 (m, 1H), 1.75 (s, 4H), 1.68 (m, 1H),
the next step without further purification.
0.97 (d, J=6.4Hz, 6H); 13C-NMR (100MHz, CDCl3) δ: 207.1,
Diphenyl sulfide (6.90g, 18.5mmol) was added to a solution 43.5, 40.1, 36.2, 31.5, 27.7, 27.4, 19.2; HR-MS (EI) m/z Calcd
of crude product 16 in toluene (9mL) at r.t. The reaction mix- for C11H16O2 (M+) 180.1150. Found 180.1154.
ture was then heated at 100°C and stirred for 7h. The solution
6-Phenylspiro[2.5]octane-4,8-dione (1e) (Table 2, Entry
was allowed to cool to r.t. and Et2O (20mL) was added, result- 4) According to the typical procedure for the synthesis of
ing in the formation of a white precipitate. The mixture was 1a, 1e was prepared from 5-phenylcyclohexane-1,3-dione
stirred at r.t. overnight and the precipitate was collected by (8e) (94mg, 0.50mmol) for 1.5h. The crude product was
suction, washed with Et2O (3mL) and dried in vacuo to pro- purified by column chromatography (silica gel, 30% EtOAc
vide 13 (3.10g, 70%) as a white solid: mp 85.0–86.0°C (lit.,17) in hexane) to provide 1e (91mg, 85%) as a white solid: mp
mp 86.5–88.0°C); IR (KBr, cm−1) ν 3065, 2986, 1448, 1274, 117.0–118.0°C; IR (KBr, cm−1) ν 1675, 1333, 1163, 768, 703;
1
1149, 1032, 755, 638; H-NMR (400MHz, CDCl3) δ: 8.13–8.09 1H-NMR (400MHz, CDCl3) δ: 7.37 (t, J=7.3Hz, 2H), 7.29 (d,
(m, 4H), 7.81–7.70 (m, 6H), 4.93–4.87 (m, 2H), 3.71–3.67 (m, J=7.3Hz, 1H), 7.24 (d, J=7.3Hz, 2H), 3.54 (tt, J=11.4, 4.1Hz,
2H); 13C-NMR (100MHz, CDCl3) δ: 135.3, 131.9, 131.1, 122.7, 1H), 2.99 (dd, J=16.9, 4.1Hz, 2H), 2.87 (dd, J=16.9, 11.4Hz,
48.5, 24.0.
2H), 1.89–1.77 (m, 4H); 13C-NMR (100MHz, CDCl3) δ: 206.0,
Typical Procedure for the Synthesis of Spirocyclopro- 141.8, 129.0, 127.3, 126.5, 46.9, 40.4, 35.7, 28.1; HR-MS (EI)
panes 1: Spiro[2.5]octane-4,8-dione (1a) (Table 1, Entry 6) m/z Calcd for C14H14O2 (M+) 214.0994. Found 214.0967.
Powdered K2CO3 (207mg, 1.5mmol) and 1,3-cyclohexanedi-
Dispiro[2.2.2.2]decane-4,10-dione (1f) (Table 2, Entry
one (8a) (56mg, 0.50mmol) were added to a suspension of 5) According to the typical procedure for the synthesis of
sulfonium salt 13 (332mg, 0.75mmol) in EtOAc (5mL). After 1a, 1f was prepared from spiro[2.5]octane-5,7-dione (8f)28)
stirring at r.t. for 1.5h, the reaction was quenched with water (69mg, 0.50mmol) for 1.5h. The crude product was purified
(10mL) and the whole mixture was extracted with EtOAc by column chromatography (silica gel, 30% EtOAc in hexane)
(2×10mL). The combined organic layer was washed with to provide 1f (72mg, 88%) as a white solid: mp 30.5–32.0°C;
1
brine (10mL) and dried over anhydrous MgSO4. The filtrate IR (KBr, cm−1) ν 2362, 1685, 1320, 1136, 1084; H-NMR
was concentrated in vacuo, and the residue was purified by (400MHz, CDCl3) δ: 2.54 (s, 4H), 1.79 (s, 4H), 0.54 (s, 4H);
column chromatography (silica gel, 30% EtOAc in hexane) 13C-NMR (100MHz, CDCl3) δ: 206.1, 48.5, 40.6, 27.4, 12.5,
to provide 1a (60mg, 87%) as a colorless oil; IR (film, cm−1) 10.5; HR-MS (EI) m/z Calcd for C10H12O2 (M+) 164.0837.
ν 2956, 1682, 1330, 1162, 1026, 956; 1H-NMR (400MHz, Found 164.0860.
CDCl3) δ: 2.67 (t, J=6.4Hz, 4H), 2.14 (quint, J=6.4Hz, 2H),
5,5-Dimethylspiro[2.5]octane-4,8-dione (1g) (Table 2, Entry
1.77 (s, 4H); 13C-NMR (100MHz, CDCl3) δ: 206.9, 40.8, 39.5, 6) According to the typical procedure for the synthesis of 1a,
27.6, 18.0; HR-MS electron ionization (EI) m/z Calcd for 1g was prepared from 4,4-dimethylcyclohexane-1,3-dione (8g)
C8H10O2 (M+) 138.0681. Found 138.0668.
(70mg, 0.50mmol) for 1.5h. The crude product was purified
6,6-Dimethylspiro[2.5]octane-4,8-dione (1b)9) (Table 2, by column chromatography (silica gel, 20% EtOAc in hexane)
Entry 1) According to the typical procedure for the syn- to provide 1g (67mg, 81%) as a colorless oil; IR (film, cm−1) ν
1
thesis of 1a, 1b was prepared from dimedone (8b) (70mg, 2966, 2361, 1684, 1329, 1058; H-NMR (400MHz, CDCl3) δ:
0.50mmol) for 1.5h. The crude product was purified by col- 2.69 (t, J=6.9Hz, 2H), 1.98 (t, J=6.9Hz, 2H), 1.75–1.69 (m,
umn chromatography (silica gel, 30% EtOAc in hexane) to 4H), 1.22 (s, 6H); 13C-NMR (100MHz, CDCl3) δ: 210.8, 207.3,