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A. Paju et al. / Tetrahedron: Asymmetry 14 (2003) 2393–2399
To a solution of the above diketone 5 (768 mg, 2.12
mmol) in THF (21 mL), 1 M HCl solution (8.5 mL)
was added. After stirring at rt for 1.5 h the mixture was
diluted with water (25 mL). The mixture was extracted
three times with EtOAc and the combined extracts
washed with brine, dried over MgSO4 and then concen-
trated. The residue was purified by flash chromatogra-
phy (silica gel, hexanes/acetone, 10:3), yielding 438 mg
(83%) of 4-benzyloxy-2-hydroxy-3-(2-hydroxyethyl)-2-
4.2.2. 3-(Benzyloxy)-3-(3-hydroxy-2-oxotetrahydrofuran-
3-yl)propanoic acids, 8b. Diketone 1b (192 mg, 0.77
mmol) was oxidized according to the typical procedure
and purified by column chromatography (petroleum
ether/acetone 10:2 to 10:5) to afford a mixture of
lactone acids 8b (123 mg, 57%) and acetals 6b and 6c
(18 mg, 9%, as a sum). 8b: 1H NMR (500 MHz CDCl3),
l 2.35 (t, 2H, J=7.1 Hz, H-4%), 2.71 (dd, 1H, J=6.8
and 16.6 Hz, H-2), 3.02 (dd, 1H, J=4.9 and 16.6 Hz,
H-2), 4.21 (m, 2H, H-3 and H-5%), 4.30 (m, 1H, H-5%),
4.60 and 4.71 (both d, 2H, J=11.2 Hz, Bn CH2),
7.23–7.23 (m, 5H,Bn); 13C NMR (125 MHz CDCl3): l
34.33 (C-4%), 35.07 (C-2), 65.86 (C-5%), 73.44 (Bn CH2),
75.90 (C-3%), 78.99 (C-3), 127.95 (o-Bn), 127.96 (p-Bn),
128.38 (m-Bn), 137.08 (s-Bn), 176.45 (C-1). 6b: (atom
numbering according to 8b), 1H NMR (500 MHz
CDCl3), l 2.15 (ddd, 1H, J=8.0, 8.7 and 13.2 Hz,
H-4%), 2.35 (ddd, 1H, J=4.0, 6.7 and 13.2 Hz, H-4%),
2.59 (dd, 1H, J=3.6 and 18.1 Hz, H-2), 2.84 (dd,
J=5.5 and 18.1 Hz, H-2), 3.50 (bs, 1H, OH), 3.96 (bs,
1H, OH), 3.97 (ddd, 1H, J=4.0, 8.0 and 8.7 Hz, H-5%),
4.05 (dd, 1H, J=3.6 and 5.5 Hz, H-3), 4.23 (dt, 1H,
J=6.7 and 2*8.7 Hz, H-5%), 4.60 and 4.71 (both d, 2H,
J=11.9 Hz, Bn CH2O), 7.30–7.40 (m, 5H, Bn); 13C
NMR (125 MHz CDCl3): l 37.87 (C-4%), 39.57 (C-2),
67.82 (C-5%), 72.21 (Bn CH2), 75.62 (C-3), 83.72 (C-3%),
101.30 (C-2%), 127.91 (o-Bn), 128.34 (p-Bn), 128.68 (m-
Bn), 136.62 (s-Bn), 205.77 (C-1). 6c: (atom numbering
1
cyclopenten-1-one 1b as a white solid; H NMR (500
MHz CDCl3): l 2.38 (dd, 1H, J=1.0 and 18.3 Hz,
H-5), 2.65 (m, 2H, H-3%), 2.68 (dd, 1H, J=5.5 and 18.3
Hz, H-5), 3.70 (bs, 1H, OH), 3.85 (ddd, 1H, J=4.3, 7.0
and 11.0 Hz, H-3¦), 3.89 (ddd, 1H, J=4.5, 6.4 and 11.0
Hz, H-3¦), 4.52 and 4.63 (both d, 2H, J=11.6 Hz, Bn
CH2), 4.53 (dd, 1H, J=1.0 and 5.5 Hz, H-4), 7.30–7.38
(m, 5H, Bn), 7.90 (bs, 1H, OH); 13C NMR (125 MHz
CDCl3): l 30.17 (C-3%), 39.50 (C-5), 60.36 (C-3¦), 71.72
(Bn CH2), 74.57 (C-4), 127.96 (o-Bn), 128.08 (p-Bn),
128.55 (m-Bn); 137.22 (s-Bn), 141.10 (C-3), 151.34 (C-
2), 199.54 (C-1); IR (KBr, cm−1): 3448, 3091, 2875,
1707, 1666, 1498, 1432, 1391, 1119, 1092, 1071; EI (m/z,
%): 218 (1.3), 157 (9.1), 142 (13.2), 112 (23.1), 108
(52.3), 107 (36.3), 91 (100).
4.2. Typical procedure for the synthesis of lactone-acids
by asymmetric oxidation of 3-hydroxyethyl-1,2-
cyclopentanediones
1
according to 8b), H NMR (500 MHz CDCl3), l 2.18
(ddd, 1H, J=4.6, 6.7 and 13.3 Hz, H-4%), 2.69 (td, 1H,
J=2*8.0, and 13.3 Hz, H-4%), 2.72 (dd, 1H, J=8.0 and
18.0 Hz, H-2), 2.73 (dd, J=8.0 and 18.0 Hz, H-2), 3.09
(bs, 1H, OH), 4.04 (t, J=2*8.0 Hz, H-3), 4.08 (dt, 1H,
J=4.6 and 2* 8.0 Hz, H-5%), 4.24 (dt, 1H, J=6.7 and
2*8.0 Hz, H-5%), 4.46 (bs, 1H, OH), 4.65 and 4.72 (both
d, 2H, J=11.9 Hz, Bn CH2O), 7.30–7.40 (m, 5H, Bn);
13C NMR (125 MHz CDCl3): l 35.35 (C-4%), 40.72
(C-2), 68.94 (C-5%), 72.33 (Bn CH2), 78.93 (C-3), 86.31
(C-3%), 102.62 (C-2%), 127.66 (o-Bn), 127.93 (p-Bn),
128.50 (m-Bn), 137.49 (s-Bn), 206.17 (C-1).
,
To a solution of Ti(OiPr)4 (0.3 mL, 1 mmol) and 4A
powdered molecular sieves (100 mg) in CH2Cl2 (6 mL),
(+)-DET (0.21 mL, 1.25 mmol for 1a and 0.27 mL, 1.6
mmol for 1b) was added and the mixture stirred for 15
min at −20°C. After the addition of cyclopentanedione
(1 mmol) in CH2Cl2 (2 mL), the mixture was stirred for
30 min. Then TBHP (0.4 mL, 2.5 mmol, 6.25 M
solution in decane) was added and the mixture kept at
−20°C for a requisite time (1a: 68 h; 1b: 45h). The
reaction was quenched by stirring with a solution of
citric acid (192 mg, 1 mmol in a mixture of 10% acetone
in ether, 30 mL) at rt for 1 h. The reaction mixture was
filtered through a path of Celite and purified by column
chromatography on silica gel (Chemapol silica gel L40/
100).
4.3. Synthesis of 1,7-dioxaspiro[4.4]nonane-2,6-diones
4.3.1. (5R)-1,7-Dioxaspiro[4.4]nonane-2,6-dione, 9. To a
solution of lactone-acid 8a (56 mg, 0.32 mmol) in
CH2Cl2 (10 mL) a crystal of p-TsOH was added. After
stirring at rt for 3.5 h the mixture was washed with
saturated NaHCO3 solution, brine, dried over Na2SO4
and concentrated. The residue was purified by flash
chromatography (silica gel, petroleum ether/acetone,
10:3) giving spirodilactone 9 as white crystals (47 mg,
94%); mp 78–79°C; ee>95%; [h]2D0=+72 (c 1.08, CHCl3);
1H NMR (500 MHz CDCl3): l 2.30 (m, 1H, H-4), 2.42
(ddd, 1H, J=7.0, 7.7 and 13.9 Hz, H-9), 2.59 (m, 1H,
H-4), 2.63 (m, 1H, H-3), 2.69 (ddd, 1H, J=5.2, 7.3 and
13.9 Hz, H-9), 2.93 (m, 1H, H-3), 4.39 (ddd, 1H,
J=5.2, 7.7 and 9.3 Hz, H-8), 4.47 (td, 1H, J=2*7.1
and 9.3 Hz, H-8); 13C NMR (125 MHz CDCl3): l 27.86
(C-3), 29.25 (C-4), 34.15 (C-9), 65.45 (C-8), 82.05 (C-5),
174.04 (C-2), 174.83 (C-6); IR (KBr, cm−1): 2947, 2922,
1786, 1248, 1224, 1069, 1007; EI (m/z, %): 156 (M+,
1.0), 112 (80.3), 98 (37.1), 84 (12.8), 70 (11.9), 56 (100);
CI (m/z, %): 157 (M+H+, 76). Anal. calcd for C7H8O4:
C, 53.85; H, 5.16. Found: C, 53.92; H, 5.17%.
4.2.1. (R)-3-(3-Hydroxy-2-oxotetrahydrofuran-3-yl)pro-
panoic acid, 8a. Diketone 1a was oxidized according to
the typical procedure and purified by column chro-
matography (petroleum ether/acetone 10:3 to 10:6) to
afford lactone acid 8a as a white solid (130 mg, 75%);
1
ee >95%; [h]2D0=+13 (c 2.04, MeOH); H NMR (500
MHz CDCl3+CD3OD): l 1.75 (ddd, 1H, J=6.2, 9.2
and 15.0 Hz, H-3), 1.91 (ddd, 1H, J=6.2, 9.2 and 15.0
Hz, H-3), 2.07 (ddd; 1H, J=6.0, 7.0 and 13.5 Hz, H-4%),
2.10 (ddd, 1H, J=7.0, 8.0 and 13.5 Hz, H-4%), 2.10
(ddd, 1H, J=7.0, 8.0 and 13.5 Hz, H-4%), 2.29 (ddd, 1H,
J=6.2, 9.2 and 16.6 Hz, H-2), 2.34 (ddd, 1H, J=6.2,
9.2 and 16.6 Hz, H-2), 4.06 (ddd, 1H, J=7.0, 8.0 and
9.0 Hz, H-5%), 4.19 (ddd, 1H, J=6.0, 7.0 and 9.0 Hz,
H-5%); 13C NMR (125 MHz CDCl3+CD3OD): l 27.57
(C-2), 30.35 (C-3), 34.71 (C-4%), 65.06 (C-5%), 73.13
(C-3%), 175.52 (C-1), 178.44 (C-2%).