1602
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Zlokazov and Veselovsky
and concentrated in vacuo, and the residue was chromatographed
on SiO2. Gradient elution with MeOBut—hexane mixtures (1 : 9
to 3 : 17 (v/v)) gave 0.32 g (99%) of acid 3 as a colorless oil.
Distillation using a shortꢀpath distillation apparatus (∼80 °C,
1 Torr) afforded 0.31 g (96%) of acid 3 as a colorless oil,
under argon to a solution of lactone 4 (0.55 g, 2.05 mmol) in
5 mL of PhH. The reaction mixture was refluxed for 2 h,
cooled to 20 °C, diluted twofold with MeOBut, and filtered
through a short SiO2 layer. The filtrate was concentrated in
vacuo and the residue was chromatographed on SiO2. Gradient
elution with MeOBut—hexane mixtures (1 : 4 to 3 : 7 (v/v))
afforded 0.28 g (97%) of lactone 6 as a colorless oil, b.p. 76 °C
(1 Torr). MS, m/z (Irel (%)): 142 [M]+ (2), 113 [M – Et]+ (33),
24
[α]D +27.7 (c 2.16, MeOH). Found (%): C, 68.02; H, 9.99.
C8H14O2. Calculated (%): C, 67.57; H, 9.92. IR (film), ν/cm–1
:
945, 975, 1220, 1250, 1275, 1380, 1417, 1453, 1710, 2880,
1
1
2930, 2965. H NMR, δ: 0.99 (d, 3 H, C(4)Me, J = 6.6 Hz);
85 (23), 84 (26), 57 (25), 56 (100), 55 (46). H NMR, δ: 0.91
1.45—1.75 (m, 2 H, C(3)H2); 1.65 (dd, 3 H, C(7)H3, J =
6.2 Hz, J = 1.3 Hz); 1.95—2.20 (m, 1 H, C(4)H); 2.20—2.48
(m, 2 H, C(2)H2); 5.22 (ddq, 1 H, C(5)H, J = 15.3 Hz, J =
7.8 Hz, J = 1.3 Hz); 5.42 (dq, 1 H, C(6)H, J = 15.3 Hz, J =
6.2 Hz). 13C NMR, δ: 17.8 (C(7)); 20.8 (MeC(4)); 31.6; 32.1;
36.5 (C(4)); 124.4 (C(6)); 136.0 (C(5)); 180.5 (C(1)).
(d, 3 H, C(5)Me, J = 7.2 Hz); 0.96 (t, 3 H, MeCH2, J =
7.2 Hz); 1.38—2.13 (m, 5 H, C(4)H2, C(5)H, MeCH2);
2.46—2.58 (m, 2 H, C(3)H2); 4.17 (ddd, 1 H, C(6)H, J =
8.5 Hz, J = 5.5 Hz, J = 2.9 Hz). 13C NMR, δ: 10.0 (MeCH2);
12.2 (MeC(5)); 24.9; 26.0; 26.6; 28.8 (C(5)); 84.4 (C(6));
171.9 (C(2)).
(1´S,5S,6R)ꢀ6ꢀ(1´ꢀIodoethyl)ꢀ5ꢀmethyltetrahydroꢀ2Hꢀpyꢀ
ranꢀ2ꢀone (4) and (1´R,5S,6S)ꢀ6ꢀ(1´ꢀiodoethyl)ꢀ5ꢀmethylꢀ
tetrahydroꢀ2Hꢀpyranꢀ2ꢀone (5). A. A solution of KI (372 mg,
2.24 mmol) and I2 (474 mg, 1.86 mmol) in 2 mL of H2O was
added at 20 °C (argon) to a solution of acid 3 (176.5 mg,
1.243 mmol) in 1 mL of a saturated solution of NaHCO3. The
reaction mixture was stirred for 40 min at 20 °C and diluted
3ꢀfold with H2O. Sodium thiosulfate was added until the mixꢀ
ture became colorless, and the mixture was extracted three
times with MeOBut. The combined ethereal layer was washed
twice with brine, dried with Na2SO4, and concentrated in vacuo.
The residue (0.31 g, yellow oil) was chromatographed on SiO2.
Elution with a MeOBut—hexane mixture (3 : 17 (v/v)) gave
153 mg (46%) of lactone 4; further gradient elution with
MeOBut—hexane mixtures (1 : 4 to 3 : 7 (v/v)) furnished 149 mg
(45%) of lactone 5.
(5S,6R)ꢀ6ꢀEthylꢀ5ꢀmethyltetrahydroꢀ2Hꢀpyranꢀ2ꢀone (7)
was prepared in a similar way from iodolactone 5. The product
20
was a colorless oil, b.p. 76 °C (1 Torr), [α]D +53.3 (c 0.99,
26
CHCl3) (cf. Ref. 8: [α]D +49.32 (c 1.034, CHCl3)). MS,
m/z (Irel (%)): 142 [M]+ (2), 113 [M – Et]+ (47), 85 (35), 84
(28), 57 (30), 56 (100), 55 (54). 1H NMR, δ: 1.00 (d, 3 H,
C(5)Me, J = 6.5 Hz); 1.02 (t, 3 H, MeCH2, J = 7.2 Hz);
1.45—2.00 (m, 5 H, C(4)H2, C(5)H, MeCH2); 2.36—2.72 (m,
2 H, C(3)H2); 3.90 (ddd, 1 H, C(6)H, J = 9.5 Hz, J = 7.5 Hz,
J = 3.3 Hz). 13C NMR, δ: 8.7 (MeCH2); 17.3 (MeC(5)); 26.1;
27.7; 29.5; 31.6 (C(5)); 86.8 (C(6)); 172.0 (C(2)).
(3S,5S,6S)ꢀ6ꢀEthylꢀ3,5ꢀdimethyltetrahydroꢀ2Hꢀpyranꢀ2ꢀone
(8). A 1.71 M hexane solution of BunLi (0.74 mL, 1.26 mmol)
was added at –78 °C under argon to a stirred solution of
(TMS)2NH (0.32 g, 1.49 mmol) in 2 mL of THF and 0.5 mL of
HMPA. After 15 min, a solution of lactone 6 (163 mg,
1.148 mmol) in 0.5 mL of THF was added to the resulting
(TMS)2NLi at the same temperature. The reaction mixture
was stirred for 30 min at –78 °C and for 1 h at –10 °C, and
cooled again to –78 °C. Methyl iodide (0.29 mL, 4.59 mmol)
was added and the mixture was kept for 1 h at –78 °C
and quenched with a saturated solution of NH4Cl. The
aqueous layer was separated and extracted three times with
MeOBut. The combined organic phase was washed with brine,
dried with MgSO4, and concentrated in vacuo, and the resiꢀ
due was chromatographed on SiO2. Gradient elution with
MeOBut—hexane mixtures (1 : 4 to 3 : 7 (v/v)) gave 149 mg
(83%) of lactone 8 as a colorless oil. MS, m/z (Irel (%)): 156 [M]+
Lactone 4. Colorless crystals, m.p. 57—60 °C. Found (%):
C, 36.24; H, 4.77; I, 47.27. C8H13IO2. Calculated (%): C, 35.84;
H, 4.89; I, 47.34. IR (CHCl3), ν/cm–1: 540, 625, 914, 995,
1027, 1060, 1070, 1140—1270, 1344, 1353, 1393, 1455, 1736,
1
2800—3100. H NMR, δ: 0.95 (d, 3 H, C(5)Me, J = 7.2 Hz);
1.65—1.82 (m, 1 H, C(4)Hax); 2.02—2.22 (m, 1 H, C(4)Heq);
2.10 (d, 3 H, H3CCHI, J = 6.5 Hz); 2.48—2.60 (m, 2 H,
C(3)H2); 4.02 (dq, 1 H, HCI, J = 10.8 Hz, J = 6.5 Hz); 4.31
(dd, 1 H, C(6)H, J = 10.8 Hz, J = 2.6 Hz). 13C NMR, δ: 10.5;
24.2; 25.4 (superimposition of two signals, DEPT data); 26.3;
29.1 (C(5)); 86.2 (C(6)); 170.3 (C(2)).
Lactone 5. Colorless crystals, m.p. 56—59 °C. Found (%):
C, 36.07; H, 5.02; I, 46.76. C8H13IO2. Calculated (%): C, 35.84;
H, 4.89; I, 47.34. IR (CHCl3), ν/cm–1: 595, 914, 991, 1020,
1039, 1067, 1118, 1140—1270, 1334, 1353, 1388, 1463, 1736,
1
(1), 127 [M – Et]+ (12), 84 (21), 70 (56), 56 (100). H NMR,
δ: 1.00 (d, 3 H, C(5)Me, J = 6.9 Hz); 1.00 (t, 3 H, MeCH2, J =
7.3 Hz); 1.25 (d, 3 H, C(3)Me, J = 7.2 Hz); 1.40—2.15 (m,
5 H, C(4)H2, C(5)H, MeCH2); 2.50—2.75 (m, 1 H, C(3)H);
4.24 (ddd, 1 H, C(6)H, J = 8.5 Hz, J = 5.8 Hz, J = 2.9 Hz).
13C NMR, δ: 7.1; 8.4; 15.1 (MeC(5)); 22.7; 26.5; 28.5; 33.1
(C(5)); 82.6 (C(6)); 174.5 (C(2)).
(4S,6S,7S)ꢀ7ꢀActoxyꢀ4,6ꢀdimethylnonanꢀ3ꢀone (serricornin
acetate) (1a). A 0.87 М solution of EtMgBr (0.73 mL,
0.63 mmol) in THF was added to a solution of lactone 8 (90 mg,
0.58 mmol) in 3 mL of THF stirred under argon at –40 °C. The
reaction mixture was stirred for an additional 2 h at the same
temperature and for 2 h at 20 °C and quenched with a saturated
solution of NH4Cl. The aqueous layer was separated and exꢀ
tracted 3 times with pentane. The combined organic phase was
dried with Na2SO4 and concentrated and the resulting hydroxy
ketone 1 was acetylated, without further purification, with a
mixture of 0.5 mL Ac2O and 0.5 mL of Py for 10 h at 20 °C.
1
2800—3100. H NMR, δ: 1.08 (d, 3 H, C(5)Me, J = 6.5 Hz);
1.48—1.70 (m, 1 H, C(4)Hax); 1.80—2.10 (m, 2 H, C(4)Heq
and C(5)H); 1.85 (d, 3 H, H3CCHI, J = 7.2 Hz); 2.40—2.73
(m, 2 H, C(3)H2); 4.12 (dd, 1 H, C(6)H, J = 8.8 Hz, J =
2.9 Hz); 4.45 (dq, 1 H, HCI, J = 7.2 Hz, J = 2.9 Hz). 13C NMR,
δ: 17.6; 21.4; 25.0; 27.0; 29.2; 30.9 (C(5)); 89.0 (C(6));
170.7 (C(2)).
B. A solution of acid 3 (14.2 mg, 0.1 mmol) and NIS
(30 mg, 0.13 mmol) in 0.5 mL of DMF was stirred under argon
for 20 h at 20 °C, diluted with water, and extracted with MeOBut.
The extract was washed twice with water and with brine, dried
with Na2SO4, and concentrated in vacuo to give 20 mg (75%)
1
of a mixture of iodolactones 4, 5 (∼3 : 2, H NMR data).
(5S,6S)ꢀ6ꢀEthylꢀ5ꢀmethyltetrahydroꢀ2Hꢀpyranꢀ2ꢀone (6).
Bun3SnH (0.78 g, 2.67 mmol) and AIBN (10 mg) were added