ꢀ
C.I. Tanase et al. / Tetrahedron 71 (2015) 6852e6859
6858
portions in 15 min and stirred overnight, monitoring the reaction
by TLC (I, twice eluted, Rf 11¼0.18). 20% Sodium thiosulfate (12 mL)
was added, the solution acidified to pH 2 with conc. HCl, extracted
with dichloromethane (4ꢂ30 mL), organic phase was washed with
water (15 mL), dried, concentrated and the product crystallized
from ethyl acetate, resulting in 206 mg (79%) of pure bis-lactone 11
as white crystals, mp 244.5e246.0 ꢃC. (lit.9 244e245.5C), IR: 2959,
2944, 1764, 1725, 1447, 1380, 1320, 1246, 1183, 1158, 1106, 1055,
48.6 (C-6a), 46.8 (C-1), 46.4 (C-3a), 40.2 (C-3), 33.7 (C-4), 31.2 (C-2).
M wt 274/276; [MꢀH]ꢀ: 273/275 [79/81(100, BP) [Brꢀ], MS: calcd
for C10H11BrO4þH: 274.9914; Found: 274.9913 [256].
4.10. Chloroetherification of ( )-(1
a,3a,3ab,6ab)-1,2,3,3a,4,6a-
hexahydropentalene-1,3-diyl)dimethanol
2.19 g (13 mmol) Diol 1 in 65 mL acetone and 6.5 mL water were
treated with 2.7 g (19.5 mmol) 97% NCS and refluxed overnight,
monitoring the reaction by TLC (hexaneeethyl acetate-acetic acid,
5:2:0.1, Rf 1¼0.08, Rf 6c¼0.22). The reaction mixture was decolorized
with active charcoal, filtered, washed with hot acetone, the filtrate
was concentrated and the concentrate was dissolved in hot toluene.
Succinimide crystallized on cooling and was filtered, the filtrate
concentrated and purified by pressure chromatography (eluent:
hexaneeethyl acetate, 2:1), resulting in 1.54 g (58.5%) of pure 6c
1032, 1005, 991. 1H NMR- (DMSO-d6, 300 MHz 65 ꢃC):
d 4.98 (dd,
1H, J¼9.9, 4.7, H-6), 4.86 (dq, 1H, J¼3.0, 1.4, H-5), 3.30 (dt, 1H, J¼9.6,
1.4, H-6a), 3.15 (tt, 1H, J¼6.6, 1.4, H-3), 3.08 (dt, 1H, J¼9.3, 1.9, H-1),
2.86 (m, H-3a), 2.47 (dt, 1H, J¼14.0, 1.9, H-2), 2.39 (ddd, 1H, J¼14.0,
9.3, 7.4, H-2), 2.18 (d, 1H, J¼14.0, H-4), 1.87 (ddd, 1H, J¼14.0, 4.1, 2.4,
H-4). 13C NMR (CDCl3, 75 MHz):
d 179.0 (C-7),171.6 (C-8), 83.5 (C-6),
78.2 (C-5), 48.3 (C-3), 47.7 (C-6a), 44.3 (C-3a), 43.5 (C-1), 38.3 (C-2),
31.2 (C-4), MS: calcd for C10H10O4þH: 195.0652, found: 195.0650
[177, 167, 149, 121].
Mother liquors were concentrated and purified by pressure
chromatography (eluent: ethyl acetateehexane, 1:1), resulting in
101 mg of pure compound 11 (total yield: 79%) (Lit.17 58%).
[(ꢁ)-((2a
a,2a1b,4a,4ab,6b,6aa)-6-chlorooctahydro-2H-pentaleno
[1,6-bc]furan-4-yl)methanol], as an oil, IR: 3428br m, 2961vs,
2936s, 2861s, 1074s, 1022s, 997vs, 947m, 812w, 719w, 672w. 1H
NMR (DMSO-d6, 300 MHz):
d
4.42 (d, 1H, J¼4.1, H-5), 4.41 (t, 1H,
J¼5.1, OH, deuterable), 4.12 (d, 1H, J¼6.3, H-6), 3.71 (d, 1H, J¼8.7, H-
7), 3.46 (dd, 1H, J¼8.7, 5.2, H-7), 3.35 (ddd, 1H, J¼10.7, 6.5, 5.1, H-8,
with TFA became dd, J¼10.7, 6.5), 3.28 (ddd, 1H, J¼10.7, 8.0, 5.1, H-8,
with TFA became dd, J¼10.7, 8.0), 3.14 (dt, 1H, J¼9.1, 6.3, H-6a), 2.78
(m, 1H, H-3a), 2.64 (dq, 1H, J¼9.5, 5.2, H-1), 2.13 (hept, 1H, J¼6.5, H-
3), 1.86 (dd, 1H, J¼14.3, 4.1, H-4), 1.83 (m, 1H, H-2), 1.76 (dd, 1H,
J¼14.3, 7.5, H-4), 0.97 (dt, 1H, J¼12.7, 9.8, H-2). 13C NMR (DMSO-d6,
4.8. Bromoetherification of ( )-(1
hexahydropentalene-1,3-diyl)dimethanol
a,3a,3ab,6ab)-1,2,3,3a,4,6a-
2.67 g (15 mmol) NBS were added to a solution of 1.68 g
(10 mmol) diole 1 in 50 mL acetone and 5 mL water and the mixture
was stirred at rt for 2 h, monitoring the reaction by TLC (I, Rf 1¼0.26,
Rf
¼0.51). The solvents were removed under vacuum, co-
75 MHz):
46.5 (C-3), 43.7 (C-3a), 43.4 (C-1), 33.8 (C-2), 32.9 (C4), MS: calcd for
10H15ClO2þH: 203.0833; Found: 203.0830 [185, 167, 149, 121].
d 89.6 (C-6), 73.7 (C-7), 65.0 (C-5), 61.8 (C-8), 53.0 (C-6a),
6b
evaporated with toluene. Most of succinimide was crystallized
from toluene (15 mL) and filtered. The filtrate was concentrated and
purified by pressure chromatography (ethyl acetateehexane, 1:1),
C
resulting in 2.39 g (96.5%) of pure product 6b [(ꢁ)-((2a
a
,2a1-
4.11. Chlorolactonization of (1R,3S,3aR,6aS)-1,2,3,3a,4,6a-hex-
ahydropentalene-1,3-dicarboxylic acid 7
b
,4 ,4a ,6 ,6a )-6-bromooctahydro-2H-pentaleno[1,6-bc]furan-4-
a
b
b
a
yl)methanol]. A fraction crystallized from ethyl acetateehexane as
white crystals has mp 62.5e63.5 ꢃC, IR: 3317, 2942, 2854, 1068,
2.55 g (13 mmol) Diacid 7 were treated with NCS as in the above
example. 2 g More NCS were used and the reflux was continued for
24 h. TLC (I, Rf 7¼0.34, Rf 8c¼0.21). After similar work-up, 2.115 g
1018, 943, 911, 647. 1H NMR (DMSO-d6, 300 MHz):
d 4.47 (d, 1H,
J¼4.3, H-5), 4.26 (d, 1H, J¼5.8, H-6), 3.61 (d, 1H, J¼8.7, H-7), 3.42 (m,
1H, H-7), 3.35 (dd, 1H, J¼10.6, 6.5, H-8), 3.27 (dd, 1H, J¼10.6, 8.0, H-
8), 3.15 (dt, 1H, J¼9.1, 5.8, H-6a), 2.81 (m, 1H, H-3a), 2.63 (dq, 1H,
J¼8.7, 5.0, H-1), 2.13 (hept, 1H, J¼6.5, H-3), 1.98 (ddd, 1H, J¼14.7,
10.4, 4.3, H-4), 1.87 (ddd, 1H, J¼12.7, 8.7, 5.0, H-2), 1.84 (dd, 1H,
J¼14.7, 7.1, H-4), 0.96 (dt, 1H, J¼12.7, 9.8, H-2). 13C NMR (DMSO-d6,
(70.5%) of pure crystallized compound 8c, (ꢁ)-(2a
a,2a1-
b,4a,4ab,6b,6aa)-6-chloro-2-oxooctahydro-2H-pentaleno[1,6-bc]
furan-4-carboxylic acid as white crystals were obtained as white
crystals, mp 228.1e229.3 ꢃC, IR: 3095s, 2970s, 1732vs, 1357m,
1223s, 1205s, 1182s, 1154s, 1064s, 867m. 1H NMR-300 MHz (DMSO-
75 MHz):
d
90.1 (C-6), 73.8 (C-7), 61.9 (C-8), 57.4 (C-5), 53.1 (C-6a),
d6, ppm, J Hz):
d
12.44 (OH), 4.90 (dd,1H, J¼7.0, 1.1, H-6), 4.60 (d, 1H,
46.3 (C-3), 44.2 (C-3a), 43.4 (C-1), 34.0 (C-2), 33.6 (C4), MS: calcd for
10H15BrO2þH: 247.0328; Found: 247.0325 [229, 167, 149, 121].
J¼3.8, H-5), 3.53 (dt, 1H, J¼11.2, 7.1, H-6a), 3.22 (dd, 1H, J¼11.0, 7.6,
H-1), 3.17 (m,1H, H-3), 3.12 (dq, 1H, J¼10.8, 7.1, H-3a), 2.35 (ddd, 1H,
J¼14.0, 11.0, 8.2, H-2), 2.02 (ddd, 1H, J¼14.0, 11.0, 7.6, H-2), 1.89 (dd,
1H, J¼15.0, 7.1, H-4), 1.77 (ddd, 1H, J¼15.0, 10.8, 3.8, H-4). 13C NMR
C
4.9. Bromolactonization of ( )-(1 ,3 ,3a ,6a )-1,2,3,3a,4,6a-
a
a
b
b
hexahydropentalene-1,3-dicarboxylic acid 7
(DMSO-d6, 75 MHz): d 179.4 (C-7),173.5 (C-8), 87.4 (C-6), 63.7 (C-5),
48.7 (C-6a), 47.0 (C-1), 46.0 (C-3a), 42.1 (C-3), 33.4 (C-4), 31.0 (C-2),
M wt 230/232 (3/1), [MꢀH]ꢀ: 229/231 (3/1) [193 (100, BP), 149],
MS: calcd for C10H11ClO4þH: 231.0419; Found: 231.0412 [213].
1.96 g (10 mmol) Diacid 7 were dissolved in 50 mL acetone and
5 mL water, 2.67 g (15 mmol) NBS were added and stirred at rt,
monitoring the reaction by TLC (I, Rf 7¼0.42, Rf 8b¼0.48). The re-
action mixture was filtered, washed with acetone (ATTENTION,
work in a ventilated hood, because some bromoacetone is formed,
which is lacrimatory), filtrated, concentrated under reduced pres-
sure and purified by pressure chromatography, resulting in 2.08 g
Acknowledgements
This project was partially funded by grant POSDRU/159/1.5/S/
135760, PN-II-ID-PCE-2011-3-0342 and by the Romanian-Austrian
bilateral mobility grant PN-II-CT-RO-AT-2013-1 (Contract 749/
10.10.2014).
(75.4%) of crystallized compound 8b (isopropanol) (ꢁ)-(2a
a,2a1-
b,4a,4ab,6b,6aa)-6-bromo-2-oxooctahydro-2H-pentaleno[1,6-bc]
furan-4-carboxylic acid as white crystals, mp 216e218 ꢃC, IR:
3456br m, 2969w, 2878w, 1704vs, 1454w, 1317m, 1271s, 1118m,
Supplementary data
1050m, 735m. 1H NMR (DMSO-d6, 300 MHz):
d
5.04 (d,1H, J¼7.0, H-
6), 4.63 (d, 1H, J¼3.6, H-5), 3.53 (dt, 1H, J¼11.0, 7.0, H-6a), 3.22 (dd,
1H, J¼11.0, 7.7, H-1), 3.20e3.10 (m, 2H, H-3, H-3a), 2.37 (ddd, 1H,
J¼13.8, 10.6, 8.8, H-2), 2.02 (ddd, 1H, J¼13.8, 10.6, 7.7, H-2), 1.95 (dd,
1H, J¼15.3, 6.5, H-4), 1.87 (ddd, 1H, J¼15.3, 10.6, 3.6, H-4). 13C NMR
Supplementary data (1H NMR and 13C NMR spectra for com-
pounds, crystallography data in Tables 1S and 2 for compounds 6b,
8, 10, 8b and 8c, Figures 1S to 4S, X-ray discussion and experimental
data) associated with this article can be found in the online version,
(DMSO-d6, 75 MHz): d 179.3 (C-7),173.4 (C-8), 87.7 (C-6), 55.0 (C-5),