Synthesis of Functionalised 4-Hydroxycyclopent-2-en-1-ones
127.68, 130.11 (CH, Ph, para), 131.64 (C, CϭCϪCO), 135.39, 14.06 (CH3, major), 17.21, 20.25, 29.09 (CH2, minor), 20.50, 21.35,
FULL PAPER
142.65 (C, Ph), 162.93 (C, CO, ester), 172.81 (C, CϭCϪCO),
32.13 (CH2, major), 54.96 (CH, major), 60.88 (OϪCH2, minor),
200.10 (C, CO, ketone). IR (KBr): ν˜ ϭ 3465 (m) (cmϪ1), 2975 (m), 61.01 (OϪCH2, major), 61.20 (CH, minor), 81.22 (C, OϪC,
1748 (s), 1450 (m), 1361 (s), 1250 (m), 1160 (s), 1057 (m), 702 (m), major), 83.00 (C, OϪC, minor), 131.28 (C, CϭCϪCO, minor),
538 (w). MS (CI, NH3, 70 eV): m/z (%) ϭ 368 [M ϩ NH4]ϩ (42), 131.66 (C, CϭCϪCO, major), 163.09 (C, CO, ester, minor), 163.40
312 (100).
(C, CO, ester, major), 184.70 (C, CϭCϪCO, minor), 185.82 (C,
CϭCϪCO, major), 199.51 (C, CO, ketone, minor), 203.4 (C, CO,
ketone, major). IR (neat): ν˜ ϭ 3467 (s) (cmϪ1), 2974 (s), 2939 (s),
1736 (s), 1715 (s), 1630 (m), 1463 (s), 1375 (s), 1306 (s), 1211 (s),
1096 (m), 1025 (s), 895 (w), 797 (w), 592(w). MS (EI, 70 eV): m/z
(%) ϭ 254 (3) [Mϩ], 225 (67), 179 (100), 57 (37); the exact molecu-
lar mass for C14H22O4 m/z ϭ 254.1518Ϯ2 ppm [Mϩ] was confirmed
by HRMS (EI, 70 eV).
Compound 9j: Starting with tert-butylacetoacetate (178 mg,
1.1 mmol, 1.1 equiv.), diisopropylamine (259 mg, 2.6 mmol,
2.5 equiv.), n-butyllithium (2.6 mmol, 2.5 equiv.) and phen-
anthrene-9,10-dione (213 mg, 1.0 mmol), 9j was isolated by chro-
matography (petroleum ether/diethyl ether, 1:1, Rf ϭ 0.33, 40 g sil-
ica gel, Ø ϭ 1.5 cm) as a colourless solid (109 mg, 31%). Reaction
time: 18 h. 1H NMR (250 MHz, [D6]DMSO, ppm): δ ϭ 0.60 (s,
2
9 H, CH3), 1.63 (s, 1 H, OH), 2.05 (d, J ϭ 18 Hz, 1 H, CH2), 2.45
Compound 9m: Starting with methyl 4-methoxyacetoacetate
(161 mg, 1.1 mmol, 1.1 equiv.), diisopropylamine (253 mg,
2.5 mmol, 2.5 equiv.), n-butyllithium (2.5 mmol, 2.5 equiv.) and
hexane-3,4-dione (114 mg, 1.0 mmol), 9m was isolated by chroma-
tography (40 g silica gel, Ø ϭ 2.0 cm). Reaction time: 22 h. Dia-
stereomer 1 (petroleum ether/diethyl ether, 2:1, Rf ϭ 0.29): Yield:
(d, 2J ϭ 18 Hz, 1 H, CH2), 6.50Ϫ6.70 (m, 4 H, CH, Ar), 6.70Ϫ6.80
3
3
(m, 2 H, CH, Ar), 7.17 (d, J ϭ 7 Hz, 1 H, CH, Ar), 7.27 (d, J ϭ
7 Hz, 1 H, CH, Ar). 13C NMR (50.3 MHz, [D6]DMSO, ppm): δ ϭ
27.59 (CH3), 47.63 (CH2), 73.51 (C, CϪOϪCϭO), 82.64 (C,
COH), 124.44, 124.68, 127.50, 128.01, 128.46, 128.99. 129.10,
132.40 (CH, Ar), 126.43 (C, CϭCϪCO), 131.39, 131.52, 133.48,
137.70 (C, Ar), 163.40 (C, CO, ester), 166.34 CϭCϪCO), 200.40
(C, CO, ketone). IR (KBr): ν˜ ϭ 3466 (s) (cmϪ1), 2983 (w), 1716
(s), 1701 (s), 1637 (s), 1451 (m), 1353 (s), 1228 (s), 1159 (s), 1051
(m), 998 (m), 759 (m), 734 (m). MS (EI, 70 eV): m/z (%) ϭ 248
(75) [Mϩ], 292 (96), 275 (100), 274 (70), 202 (50), 57 (50); the exact
molecular mass for C22H20O4 m/z ϭ 348.1362Ϯ2 ppm [Mϩ] was
confirmed by HRMS (EI, 70 eV).
1
29 mg (12%) as a yellow oil. H NMR (300 MHz, CDCl3, ppm):
3
3
δ ϭ 0.83 (t, J ϭ 8 Hz, 3 H, CH3), 1.19 (t, J ϭ 8 Hz, 3 H, CH3),
3
2
3
1.55 (dq, J ϭ 8, J ϭ 14 Hz, 1 H, HϪHCϪCOH), 1.91 (dq, J ϭ
2
3
2
8, J ϭ 14 Hz, 1 H, HϪHCϪCOH), 2.57 (dq, J ϭ 8, J ϭ 12 Hz,
1 H, HϪHCϪCϭ), 2.81 (dq, 3J 8, 2J
ϭ
ϭ
12 Hz, 1 H,
HϪHCϪCϭ), 3.37 (s, 1 H, CH), 3.62 (s, 3 H, OϪCH3), 3.81 (s,
3 H, OϪCH3). 13C NMR (50.3 MHz, CDCl3, ppm): δ ϭ 7.99,
13.55 (CH3), 21.20, 29.92 (CH2), 51.98, 59.07 (OϪCH3), 78.00 (C,
OϪC), 81.12 (CH), 129.66 (C, CϭCϪCO), 163.15 (C, CO, ester),
189.63 (C, CϭCϪCO), 197.41 (C, CO, ketone). IR (neat): ν˜ ϭ
3486 (m) (cmϪ1), 2971 (m), 2940 (m), 1744 (s), 1722 (s), 1626 (m),
1461 (m), 1439 (m), 1308 (m), 1220 (s), 1105 (m), 1024 (m), 790
(w). MS (EI, 70 eV): m/z (%) ϭ 213 (40), 210 (55), 57 (100), 43
(48). MS (CI, NH3, 70 eV): m/z (%) ϭ 502 (100) [2M ϩ NH4ϩ],
260 (45) [M ϩ NH4ϩ]. Diastereomer 2 (petroleum ether/diethyl
ether, 1:1.5, Rf ϭ 0.29): Yield: 79 mg (33%) as a yellow oil. 1H
NMR (300 MHz, CDCl3, ppm): δ ϭ 0.65 (t, 3J ϭ 8 Hz, 3 H, CH3),
Compound 9k: Starting with benzyl acetoacetate (212 mg,
1.1 mmol, 1.1 equiv.), diisopropylamine (253 mg, 2.5 mmol,
2.5 equiv.), n-butyllithium (2.5 mmol, 2.5 equiv.) and hexane-3,4-
dione (114 mg, 1.0 mmol), 9k was isolated by chromatography
(petroleum ether/diethyl ether, 1:2, Rf ϭ 0.28, 40 g silica gel, Ø ϭ
1.5 cm) as a yellow oil (38 mg, 13%). Reaction time: 25 h. 1H NMR
3
(200 MHz, CDCl3, ppm): δ ϭ 0.89 (t, J ϭ 7 Hz, 3 H, CH3), 1.17
3
(t, J ϭ 8 Hz, 3 H, CH3), 1.60Ϫ2.00 (AB system, additional split-
2
2
ting by J؊coupling, 2 H, HOCϪCH2), 2.51 (d, J ϭ 18 Hz, 1 H,
HϪHCϪCO), partly overlapped by 2.50Ϫ2.80 (m, 2 H,
ϭCϪCH2), partly overlapped by 2.68 (d, 2J ϭ 18 Hz, 1 H,
HϪHCϪCO), 5.30 (s, 2 H, OϪCH2), 7.30Ϫ7.50 (m, 5 H, CH, Ph).
13C NMR (75.5 MHz, CDCl3, ppm): δ ϭ 8.34, 13.39 (CH3), 20.43,
31.07 (CH2), 48.46 (COϪCH2), 66.74 (OϪCH2), 79.71 (C, OϪC),
128.23, 128.50 (CH, Ph, ortho and meta), 128.26 (CH, Ph, para),
131.96, 135.28 (C, Ph, CϭCϪCO), 162.87 (C, CO, ester), 187.47
(C, CϭCϪCO), 199.78 (C, CO, ketone). IR (neat): ν˜ ϭ 3441 (s)
(cmϪ1), 3037 (w), 2976, (m), 2939 (m), 1736 (s), 1715 (s), 1633 (m),
1458 (m), 1384 (m), 1305 (m), 1196 (m), 1097 (m), 1024 (m), 749
(w), 699 (w). MS (EI, 70 eV): m/z (%) ϭ 288 (2) [Mϩ], 164 (35), 91
(100); the exact molecular mass for C16H18O4 m/z ϭ 288.1362Ϯ2
ppm [Mϩ] was confirmed by HRMS (EI, 70 eV).
3
3
2
1.20 (t, J ϭ 8 Hz, 3 H, CH3), 1.72 (dq, J ϭ 8, J ϭ 14 Hz, 1 H,
HϪHCϪCOH), 1.99 (dq, 3J
ϭ
8, 2J
ϭ
14 Hz, 1 H,
3
HϪHCϪCOH), 2.54 (dq, J ϭ 8, 2J ϭ 12 Hz, 1 H, HϪHCϪCϭ),
2.83 (dq, 3J ϭ 8, 2J ϭ 12 Hz, 1 H, HϪHCϪCϭ), 3.68 (s, 3 H,
OϪCH3), 3.81 (s, 3 H, OϪCH3), 3.91 (s, 1 H, CH). 13C NMR
(50.3 MHz, CDCl3, ppm): δ ϭ 9.16, 13.16 (CH3), 20.57, 29.55
(CH2), 52.00, 60.29 (OϪCH3), 82.57 (C, OϪC), 90.00 (CH), 129.52
(C, CϭCϪCO), 162.84 (C, CO, ester), 183.65 (C, CϭCϪCO),
196.27 (C, CO, ketone). IR (neat): ν˜ ϭ 3460 (s) (cmϪ1), 2977 (s),
2943 (s), 1741 (s), 1726 (s), 1618 (m), 1440 (s), 1310 (s), 1221 (s),
1129 (s), 1028 (s), 841 (w), 787 (w), 732 (m). MS (EI, 70 eV): m/z
(%) ϭ 242 (24) [Mϩ], 213 (97), 210 (100); the exact molecular mass
for C12H18O5 m/z ϭ 242.1154Ϯ2 ppm [Mϩ] was confirmed by
HRMS (EI, 70 eV).
Compound 9l: Starting with ethyl 3-oxohexanoate (174 mg,
1.1 mmol, 1.1 equiv.), diisopropylamine (253 mg, 2.5 mmol, Compound 9n: Starting with N,N-diethylacetylacetamide (173 mg,
2.5 equiv.), n-butyllithium (2.5 mmol, 2.5 equiv.) and hexane-3,4-
dione (114 mg, 1.0 mmol), 9l was isolated by chromatography (pen-
1.1 mmol, 1.1 equiv.), diisopropylamine (253 mg, 2.5 mmol,
2.5 equiv.), n-butyllithium (2.5 mmol, 2.5 equiv.) and butane-2,3-di-
tane/diethyl ether, 2:1, Rf ϭ 0.21, 40 g silica gel, Ø ϭ 2.0 cm) as a one (86 mg, 1.0 mmol), 9n was isolated by chromatography (diethyl
yellow oil (124 mg, 49%, two diastereomers, dr ϭ 4:1). Reaction
ether/acetone, 10:1, Rf ϭ 0.21, 40 g silica gel, Ø ϭ 2.0 cm) as a yel-
low oil (146 mg, 65%). Reaction time: 19 h. H NMR (250 MHz,
1
1
time: 25 h. H NMR (300 MHz, CDCl3, major, ppm): δ ϭ 0.82 (t,
3
3
3J ϭ 8 Hz, 3 H, CH3), 1.03 (t, J ϭ 7 Hz, 3 H, CH3), 1.18 (t, J ϭ CDCl3, ppm): δ ϭ 1.08 (t, 3J ϭ 7 Hz, 3 H, CH3), 1.18 (t, 3J ϭ
8 Hz, 3 H, CH3), 1.30 (t, 3J ϭ 7 Hz, 3 H, CH3), 1.50Ϫ1.70 (m, 2 H, 7 Hz, 3 H, CH3), 1.48 (s, 3 H, CH3), 2.06 (s, 3 H, CH3), 2.58 (d,
CH2), 1.70Ϫ1.95 (m, 2 H, CH2), 2.25 (t, 3J ϭ 7 Hz, 1 H, CH), 2J ϭ 18 Hz, 1 H, CH2), 2.68 (d, 2J ϭ 18 Hz, 1 H, CH2), 3.14 (q,
3
3
2.40Ϫ2.60 (m, 1 H, CH2), 2.60Ϫ2.80 (m, 1 H, CH2), 4.26 (q, J ϭ
7 Hz, 2 H, OϪCH2). 13C NMR (50.3 MHz, CDCl3, ppm): δ ϭ 8.29 (50.3 MHz, CDCl3, ppm): δ ϭ 11.18, 13.01, 14.36, 25.67 (CH3),
(CH3, major, minor), 9.55, 13.19, 13.20 (CH3, minor) 12.47, 13.47, 39.21, 42.88 (CH2), 51.19 (COϪCH2), 77.63 (C, COH), 137.76 (C,
3J ϭ 7 Hz, 2 H, CH2), 3.46 (q, J ϭ 7 Hz, 2 H, CH2). 13C NMR
Eur. J. Org. Chem. 2005, 532Ϫ542
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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