P. Camps, D. Lozano, M. Font-Bardia
FULL PAPER
4.81 mmol) in CCl4 (14.6 mL) under an Ar atmosphere. The re-
sulting orange-colored stirred suspension was heated at 65 °C for
15 min, and then at 90 °C for 1 h. The grey suspension was then
cooled with an ice/water bath; the solid precipitate was removed by
filtration, and washed with cold CH2Cl2 (3ϫ 5 mL). The combined
filtrate and washings were washed with saturated aqueous
NaHCO3 (3ϫ 10 mL) and brine (10 mL), dried (anhydrous
Na2SO4), and concentrated in vacuo to give crude bromide 5
(1.31 g, 94%) as a yellow oil, which was used as such in the next
CH2OAc), 6.87 [pseudo t, J = 2.2 Hz, 2 H, 5(6)-H] ppm. NOESY:
irradiation at δ = 6.87 ppm shows an NOE with the protons ap-
pearing at δ = 3.74 [1(4)-H] and 4.25 (syn-CH2OAc) ppm. 13C
NMR: δ = 20.7 (CH3, CH3COO), 20.8 (CH3, CH3COO), 52.2
(CH3, 2 COOCH3), 56.7 [CH, C-1(4)], 63.7 (CH2, CH2OAc), 63.8
(CH2, CH2OAc), 85.7 (C, C-7), 140.9 [CH, C-5(6)], 150.2 [C, C-
2(3)], 164.7 [C, C-2(3)-COOMe], 170.50 (C, anti-CH3COO), 170.54
(C, syn-CH3COO) ppm.
Dimethyl (1RS,3aRS,4SR,6aSR,7SR)-3a-(Hydroxymethyl)-
3,3a,4,6a-tetrahydro-1H-1,4-methanocyclopenta[c]furan-1,7-dicarb-
oxylate (8): Anhydrous K2CO3 (40 mg, 0.29 mmol) was added to a
solution of diacetate 7 (413 mg, 1.17 mmol) in anhydrous MeOH
(2.5 mL), and the mixture was stirred at 30 °C for 2 h. The mixture
was cooled to 0 °C (ice/water bath), and filtered. The solid was
washed with MeOH (4ϫ 5 mL). The combined filtrate and wash-
ings were concentrated in vacuo to give a brown solid (369 mg),
containing a stereoisomeric mixture of 8 and its C-7 epimer 9, in
a ratio 8/9 = 9:1 (by 1H NMR spectroscopy). This mixture was
subjected to column chromatography [35–70 μm silica gel (11 g),
hexane/EtOAc mixtures]. On elution with hexane/EtOAc, 3:2 to
1:1, a stereoisomeric mixture of 8 and 9 (168 mg), in a ratio 8/9 =
9:1, was obtained. By heating this solid in refluxing EtOAc
(0.5 mL), an analytical sample of 8 (101 mg, 32%) was obtained as
a white solid. m.p. 118–120 °C (EtOAc). Rf (silica gel, 10 cm, hex-
step. R (hexane/EtOAc, 1:1): 0.42. IR (ATR): ν = 3067 (w), 2952
˜
f
(m), 2893 (w), 1736 (s), 1466 (m), 1437 (m), 1379 (s), 1364 (s), 1232
(s), 1183 (m), 1043 (s), 981 (m), 906 (m), 809 (m), 786 (m), 765
(m) cm–1. HRMS: calcd. for [C11H1579BrO4 + H]+ 291.0226; found
292.0219. 1H NMR: δ = 2.05 (s, 3 H) and 2.09 (s, 3 H) (2
CH3COO), 2.35 (dd, J = 15.6, JЈ = 2.4 Hz, 1 H, 5-Ha), 2.47 (dd, J
= 15.6, JЈ = 7.6 Hz, 1 H, 5-Hb), 3.95 (d, J = 11.0 Hz, 1 H) and
4.10 (d, J = 11.0 Hz, 1 H) (CH2OAc), 4.20 (s, 2 H, CH2OAc), 5.05–
5.08 (ddt, J = 7.6, JЈ = 2.4, JЈЈ = 0.8 Hz, 1 H, 4-H), 5.80 (d, J =
5.6 Hz, 1 H, 2-H), 6.08 (dd, J = 5.4, JЈ = 2.2 Hz, 1 H, 3-H) ppm.
13C NMR: δ = 20.75 (CH3) and 20.85 (CH3) (2 OCOCH3), 41.0
(CH2, C-5), 52.7 (CH, C-4), 53.5 (C, C-1), 65.6 (CH2) and 66.7
(CH2, 2 CH2OAc), 135.7 (CH) and 136.0 (CH, C-2 and C-3), 170.7
(C) and 170.8 (C, 2 CH3COO) ppm.
Cyclopenta-2,4-diene-1,1-diylbis(methylene) Diacetate (6): A mag-
netically stirred solution of bromo diacetate 5 (3.79 g, 13.0 mmol)
in anhydrous quinoline (6.9 mL, 58.6 mmol) under an Ar atmo-
sphere was heated at 180 °C for 1 h. The dark mixture was cooled
with an ice/water bath, then Et2O (15 mL) was added. The mixture
was stirred for 5 min, and then it was washed with HCl (2 n aq.;
4ϫ 10 mL) and water (20 mL). The brown organic phase was dried
(anhydrous Na2SO4), and concentrated in vacuo to give diene 6
(2.38 g, 88%) as a brown oil, which was used as such in the next
ane/EtOAc, 3:7): 0.28. IR (ATR): ν = 3488 (m), 3426 (m), 2954
˜
(w), 2903 (w), 2871 (w), 1721 (s), 1439 (m), 1325 (s), 1217 (s), 1196
(s), 1170 (s), 1156 (s), 1064 (s), 1037 (s), 1016 (s), 1000 (m), 926
(m), 888 (m), 730 (s), 658 (m) cm–1. C13H16O6 (268.26): C 58.20,
H 6.01; found C 58.20, H 6.14. HRMS: calcd. for [C13H16O6
+
1
Na]+ 291.0839; found 291.0841. H NMR: δ = 1.59 (s, 1 H, OH),
2.74 (s, 1 H, 7-H), 3.07–3.09 (m, 1 H, 6a-H), 3.19–3.21 (m, 1 H,
4-H), 3.62 (br. d, J = 9.0 Hz, 1 H) and 3.68 (br. d, J = 9.0 Hz, 1
H, CH2OH), 3.70 (s, 3 H, C-1-COOCH3), 3.81 (s, 3 H, C-7-
COOCH3), 3.96 (d, J = 8.8 Hz, 1 H) and 4.00 (d, J = 8.8 Hz, 1 H,
3-Ha and 3-Hb), 5.93–5.95 (ddd, J = 5.8, JЈ = 3.0, JЈЈ = 1.0 Hz, 1
H, 6-H), 6.39–6.42 (dd, J = 5.8, JЈ = 3.0 Hz, 1 H, 5-H) ppm. 13C
NMR: δ = 48.0 (CH, C-4), 52.2 (CH3, C-1-COOCH3), 52.6 (CH3,
C-7-COOCH3), 56.9 (CH, C-7), 59.1 (CH, C-6a), 59.6 (CH2,
CH2OH), 68.6 (CH2, C-3), 75.4 (C, C-3a), 85.7 (C, C-1), 128.0
(CH, C-6), 139.8 (CH, C-5), 170.9 (C, C-7-COOMe), 171.1 (C, C-
1-COOMe) ppm.
step. An analytical sample of
6 was obtained by column
chromatography of a sample of the above product (205 mg) [35–
70 μm silica gel (6.1 g), pentane/EtOAc mixtures]. On elution with
pentane/EtOAc, 96:4, diene 6 (165 mg) was isolated as a pale yellow
oil that solidified on standing. m.p. 42–43 °C. Rf (silica gel, 10 cm,
hexane/EtOAc, 1:1): 0.56. IR (ATR): ν = 3076 (w), 2978 (m), 2959
˜
(m), 2897 (m), 2850 (w), 1736 (s), 1466 (m), 1430 (m), 1376 (s),
1227 (s), 1078 (m), 1032 (s), 978 (s), 922 (m), 896 (m), 753 (s) cm–1.
C11H14O4 (210.23): calcd. C 62.85, H 6.71; found C 62.97, H 6.90.
HRMS: calcd. for [C11H14O4 + NH4]+ 228.1230; found 228.1233;
1
calcd. for [C11H14O4 + H]+ 211.0965; found 211.0965. H NMR: δ
NMR spectroscopic data of 9: A mixture of 8 and 9 (120 mg) in a
ratio of ca. 1.5:10 was obtained by silica gel column chromatog-
raphy as part of an operation to prepare diol 13 (see below). The
NMR spectroscopic data for 9 are given based on this mixture. 1H
NMR: δ = 1.53 (br. s, 1 H, OH), 3.02–3.04 (m, 1 H, 6a-H), 3.12–
3.15 (m, 1 H, 4-H), 3.34 (d, J = 4.4 Hz, 1 H, 7-H), 3.57 (s, 3 H, C-
1-COOMe), 3.61 (br. d, J = 11.2 Hz, 1 H) and 3.69 (br. d, J =
11.2 Hz, 1 H, CH2OH), 3.77 (s, 3 H, C-7-COOMe), 3.82 (d, J =
9.0 Hz, 1 H) and 3.98 (d, J = 9.0 Hz, 1 H, 3-Ha and 3-Hb), 6.10
(ddd, J = 5.6, JЈ = 3.2, JЈЈ = 0.8 Hz, 1 H, 6-H), 6.16 (dd, J = 5.6,
JЈ = 2.8 Hz, 1 H, 5-H) ppm. 13C NMR: δ = 49.0 (CH, C-4), 51.7
(CH3, C-1-COOCH3), 52.3 (CH3, C-7-COOCH3), 55.8 (CH, C-6a),
55.9 (CH, C-7), 59.4 (CH2, CH2OH), 68.2 (CH2, C-3), 73.1 (C, C-
3a), 88.8 (C, C-1), 129.6 (CH, C-6), 135.7 (CH, C-5), 169.3 (C, C-
7-COOMe), 169.7 (C, C-1-COOMe) ppm.
= 2.08 (s, 6 H, 2 CH3COO), 4.07 (s, 4 H, 2 CH2OAc), 6.33–6.35
[m, 2 H, 2(5)-H], 6.47–6.48 [m, 2 H, 3(4)-H] ppm. 13C NMR: δ =
20.9 (CH3, 2 OCOCH3), 59.5 (C, C-1), 63.6 (CH2, 2 CH2OAc),
133.6 [CH, C-2(5)], 137.4 [CH, C-3(4)], 170.7 (C, 2 CH3COO) ppm.
Dimethyl 7,7-Bis(acetoxymethyl)bicyclo[2.2.1]hepta-2,5-diene-2,3-
dicarboxylate (7): A solution of crude diene 6 (624 mg, 2.97 mmol)
and dimethyl acetylenedicarboxylate (0.55 mL, 633 mg, 4.45 mmol)
in toluene (5 mL) was heated at 80 °C for 72 h. The solution was
then cooled to room temperature, and the solvent was removed in
vacuo. The brown oily residue was subjected to column chromatog-
raphy [35–70 μm silica gel (25 g), hexane/EtOAc mixtures]. On elu-
tion with hexane/EtOAc, 3:1, adduct 7 (820 mg, 78%) was isolated
as a pale yellow oil. Rf (silica gel, 10 cm, hexane/EtOAc, 3:7): 0.47.
IR (ATR): ν = 3000 (w), 2955 (w), 1731 (s), 1713 (s), 1630 (m),
˜
1435 (m), 1376 (m), 1366 (m), 1317 (m), 1218 (s), 1099 (m), 1031 Dimethyl (1RS,3aRS,4SR,6aSR,7SR)-3a-{[(Methylsulfonyl)-
(s), 734 (m) cm–1. C17H20O8 (352.34): C 57.95, H 5.72%; found C oxy]methyl}-3,3a,4,6a-tetrahydro-1H-1,4-methanocyclopenta[c]-
57.98, H 5.89%. HRMS: calcd. for [C17H20O8 + H]+ 353.1231; furan-1,7-dicarboxylate (10): Methanesulfonyl chloride (0.03 mL,
1
found 353.1239. H NMR: δ = 2.028 (s, 3 H) and 2.031 (s, 3 H, 2
CH3COO), 3.74 [pseudo t, J = 2.0 Hz, 2 H, 1(4)-H], 3.79 [s, 6 H,
C-2(3)-COOMe], 4.25 (s, 2 H, syn-CH2OAc) and 4.29 (s, 2 H, anti-
0.36 mmol) was added dropwise to a cold (0 °C, ice/water bath)
and magnetically stirred solution of alcohol 8 (80 mg, 0.3 mmol)
and anhydrous Et3N (0.1 mL, 0.69 mmol) in CH2Cl2 (3.3 mL) un-
5016
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5013–5020