Synthesis of (2R,4R)-Supellapyrone
FULL PAPER
was purified by silica gel column chromatography (4.0 g, hexane/ CDCl3): δ ϭ 0.81 (d, J ϭ 6.2 Hz, 3 H, 4Ј-CH3), 0.83 (d, J ϭ 6.4 Hz,
ethyl acetate, 30:1) to give (2R,4R)-26 (125 mg, 63%) as an oil. Ϫ 3 H, 2Ј-CH3), 0.88 (t, J ϭ 7.0 Hz, 3 H, 7-H3), 1.0Ϫ1.25 (m, 4 H,
n2D3 ϭ 1.4727. Ϫ [α]2D5 ϭ Ϫ3.56 (c ϭ1.04 in CHCl3). Ϫ IR (film): 5Ј,6Ј-H2), 1.28 (dt, J ϭ 14.9, 7.0 Hz, 2 H, 3Ј-H2), 1.36 (d, J ϭ
ν˜max ϭ 1725 cmϪ1 (s, CϭO), 1135 (s). Ϫ 1H NMR (500 MHz,
CDCl3): δ ϭ 0.84 (d, J ϭ 6.7 Hz, 3 H, 4Ј-CH3), 0.89 (t, J ϭ
7.4 Hz, 3 H, 3-CH3), 1.49 (sext-like, J ϭ 6.8 Hz, 1 H, 4Ј-H), 1.61
(sext-like, J ϭ 6.3 Hz, 1 H, 2Ј-H), 1.87 (dd, J ϭ 14.2, 8.0 Hz, 1 H,
11.6 Hz, 3 H, 7Ј-H3), 0.90 (d, J ϭ 10.7 Hz, 3 H, 2Ј-CH3), 0.95Ϫ1.65 1Ј-H), 2.00 (dt, J ϭ 14.0, 4.9 Hz, 1 H, 1Ј-H), 3.05 (m, 1 H, 3-H),
(m, 10 H, 1Ј,3Ј,5Ј,6Ј-H2, 2Ј,4Ј-H), 1.92 (dt, J ϭ 4.6, 1.5 Hz, 3 H, 4.68 (d, J ϭ 15.5 Hz, 1 H, 6-H), 4.75 (d, J ϭ 15.5 Hz, 1 H, 6-H),
3-CH3), 2.57 (br. s, 1 H, 5-H), 4.05 (dt, J ϭ 7.7, 10.1 Hz, 1 H, 6-H),
4.35 (ddd, J ϭ 11.0, 7.4, 4.9 Hz, 1 H, 6-H), 6.53 (d, J ϭ 22.9 Hz, 1
H, 4-H). Ϫ C15H26O2 (238.4): calced. C 75.58, H 10.99; found C
75.58, H 10.86.
5.45 (s, 1 H, 4-H).
(2S,4R) Isomer: In the same manner as described above, (2S,4R)-
26 (22 mg, 0.092 mmol) gave (2S,4R)-27 (16 mg, 67%) as an oil.
Its IR and 1H NMR spectra are identical to those reported for
(2R,4S)-27.
(2S,4S) Isomer: In the same manner as described above, (2S,4S)-25
(381 mg, 1.49 mmol) gave (2S,4S)-26 (251 mg, 71%) as an oil. Ϫ
n2D5 ϭ 1.4721. Ϫ [α]2D5 ϭ ϩ2.90 (c ϭ 1.14 in CHCl3). Ϫ Its IR and
1H NMR spectra are identical to those reported for (2R,4R)-26. Ϫ
C15H26O2 (238.4): calcd. C 75.58, H 10.99; found C 75.57, H 10.84.
(b): To a solution of (2R,4R)-27 (37 mg, 0.16 mmol) in chloroform
(0.30 mL) was added dropwise a solution of bromine in carbon
tetrachloride (0.55 , 0.40 mL, 0.22 mmol) at 0 °C. After 30 min,
the solution was warmed to room temperature and stirred for
17.5 h in the dark, and then concentrated in vacuo. The residue
was rapidly diluted with chloroform (0.30 mL), and DBU (96 µL,
0.64 mmol) was added. The mixture was stirred for 1 h at room
temperature. It was poured into a saturated aqueous NH4Cl solu-
tion, and extracted with diethyl ether. The extract was washed with
a saturated aqueous NH4Cl solution, water and brine. The extract
was dried with MgSO4, and concentrated in vacuo. The residue was
purified by silica gel column chromatography (1.0 g, hexane/ethyl
(2R,4S) Isomer: In the same manner as described above, (2R,4S)-
25 (143 mg, 0.59 mmol) gave (2R,4S)-26 (72 mg, 51%) as an oil. Ϫ
n2D3 ϭ 1.4683. Ϫ [α]2D5 ϭ Ϫ26.9 (c ϭ 1.10 in CHCl3). Ϫ IR (film):
ν˜max ϭ 1725 cmϪ1 (s, CϭO), 1135 (s). Ϫ 1H NMR (500 MHz,
CDCl3): δ ϭ 0.83 (d, J ϭ 6.4 Hz, 3 H, 4Ј-CH3), 0.88 (t, J ϭ 7.3 Hz,
3 H, 7Ј-H3), 0.88 (d, J ϭ 10.7 Hz, 3 H, 2Ј-CH3), 1.0Ϫ1.4 (m, 8 H,
3Ј,5Ј,6Ј-H2, 1Ј,2Ј,4Ј-H), 1.50 (dq, J ϭ 20.8, 7.3 Hz, 1 H, 1Ј-H), 1.92
(q, 1.5 Hz, 3 H, 3-CH3), 2.57 (br. s, 1 H, 5-H), 4.05 (ddd, J ϭ 11.0,
7.3, 5.3 Hz, 1 H, 6-H), 4.35 (quint-like, J ϭ 5.5 Hz, 1 H, 6-H), 6.53
(br. d, J ϭ 15.3 Hz, 1 H, 4-H). Ϫ C15H26O2 (238.4): calcd. C 75.58,
H 10.99; found C 75.26, H 10.46.
acetate, 30:1) to give (2R,4R)-1 (23 mg, 61%) as an oil. Ϫ n2D6
ϭ
1.4950. Ϫ [α]2D3 ϭ ϩ5.20 (c ϭ 1.15 in diethyl ether). Ϫ IR (film):
ν˜max ϭ 2955 cmϪ1 (s), 2925 (s), 1715 (s, CϭO), 1650 (m), 1570 (m),
1455 (m), 1380 (m), 1265 (m), 1160 (m), 1040 (m), 990 (m), 760
1
(2S,4R) Isomer: In the same manner as described above, (2S,4R)-
25 (148 mg, 0.61 mmol) gave (2S,4R)-26 (73 mg, 50%)as an oil. Ϫ
n2D3 ϭ 1.4680. Ϫ [α]2D5 ϭ ϩ27.0 (c ϭ 1.10 in CHCl3). Ϫ Its IR and
1H NMR spectra are identical to those reported for (2R,4S)-26. Ϫ
C15H26O2 (238.4): calcd. C 75.58, H 10.99; found C 75.38, H 10.78.
(m). Ϫ H NMR (500 MHz, C6D6): δ ϭ 0.61 (d, J ϭ 6.4 Hz, 3 H,
2ЈCH3), 0.75Ϫ0.85 (m, 1 H, 5Ј-H), 0.80 (dd, J ϭ 12.2, 2.3 Hz, 3 H,
4Ј-CH3), 0.90 (t, J ϭ 10.4 Hz, 3 H, 7Ј-H3), 0.97Ϫ1.1 (m, 1 H, 5Ј-
H), 1.04 (q, J ϭ 7.3 Hz, 1 H, 6Ј-H), 1.15Ϫ1.35 (m, 3 H, 3Ј,4Ј,6Ј-
H), 1.377 (q-like, J ϭ 5.5 Hz, 2 H, 1Ј,3Ј-H), 1.384 (dd, J ϭ 21.4,
8.9 Hz, 1 H, 2Ј-H), 1.78 (dq, J ϭ 3.35, 12.2 Hz, 1 H, 1Ј-H), 1.86
(d, J ϭ 0.6 Hz, 3 H, 3-CH3), 6.32 (q, J ϭ 1.2 Hz, 1 H, 4-H), 6.55
(br. s, 1 H, 2-H). Ϫ 13C NMR (125.65 MHz, C6D6): δ ϭ 14.6, 17.1,
19.6, 20.2, 30.0, 30.3, 36.6, 39.2, 44.7, 117.2, 125.7, 140.5, 146.1,
162.0. Ϫ The spectral data of (2R,4R)-1 are identical to those re-
ported previously.[1,2,7,8] Ϫ HREI-MS [C15H24O2]: calcd. 236.1776;
found 236.1776.
(2R,4R)-5-(2,4-Dimethylheptyl)-3-methyl-2H-pyran-2-one (Supella-
pyrone, 1)
(a): To a stirred solution of α,β-unsaturated lactone (2R,4R)-26
(51 mg, 0.21 mmol) in THF (0.75 mL) and hexamethylphosphoric
triamide (HMPA, 0.15 mL), was added dropwise a solution of pot-
assium hexamethyldisilazide in toluene (0.5 , 0.84 mL,
0.42 mmol). After 1 h, HCl (1 , 0.1 mL) was added, and 30 s later
saturated aqueous NaHCO3 solution (1.0 mL) was added. The
mixture was allowed to warm to room temperature, diluted with
water, and extracted with diethyl ether. The extract was washed
with water, saturated aqueous NaHCO3 solution and brine. The
extract was dried with Na2SO4, and concentrated in vacuo. The
residue was filtered through a silica gel column to give (2R,4R)-27
(37 mg, 74%) as an oil, which was used without further purifica-
tion. Ϫ IR (film): ν˜max ϭ 1745 cmϪ1 (s, CϭO), 1200 (m, CϪO). Ϫ
1H NMR (300 MHz, CDCl3): δ ϭ 0.8Ϫ0.9 (m, 9 H, 2Ј,4Ј-CH3, 7-
H3), 0.9Ϫ1.7 (m, 8 H, 3Ј,5Ј,6Ј-H2, 2Ј,4Ј-H), 1.36 (d, J ϭ 7.4 Hz, 3
H, 3-CH3), 1.78 (dd, J ϭ 9.0, 13.5 Hz, 1 H, 1Ј-H), 2.07 (dt, J ϭ
6.0, 13.5 Hz, 1 H, 1Ј-H), 3.04 (br. s, 1 H, 3-H), 4.63Ϫ4.80 (m, 2 H,
6-H), 5.45 (s, 1 H, 4-H).
(2S,4S) Isomer: In the same manner as described above, (2S,4S)-27
(49 mg, 0.21 mmol) gave (2S,4S)-1 (40 mg, 81%) as an oil. Ϫ n2D6
ϭ
1
1.4923. Ϫ [α]2D3 ϭ Ϫ5.82 (c ϭ 1.11 in diethyl ether). Ϫ Its IR, H
and13C NMR spectra are identical to those reported for (2R,4R)-
1. Ϫ HREI-MS [C15H24O2]: calcd. 236.1776; found 236.1777.
(2R,4S) Isomer: In the same manner as described above, (2R,4S)-
27 (24 mg, 0.10 mmol) gave (2R,4S)-1 (15 mg, 64%) as an oil. Ϫ
n2D4 ϭ 1.5159. Ϫ [α]2D3 ϭ 29.1 (c ϭ 0.75 in CHCl3). Ϫ IR (film):
ν˜max ϭ 2955 cmϪ1 (s), 2925 (s), 1715 (s), 1650 (m), 1570 (m), 1455
(m), 1380 (m), 1265 (m), 1160 (m), 1040 (m), 990 (m), 760 (m). Ϫ
1H NMR (500 MHz, C6D6): δ ϭ 0.61 (d, J ϭ 6.4 Hz, 3 H, 2Ј-CH3),
0.75 (d, J ϭ 6.4 Hz, 3 H, 4Ј-CH3), 0.90 (t, J ϭ 7.1 Hz, 3 H, 7Ј-H3),
0.85Ϫ0.95 (m, 2 H, 5Ј-H2), 1.0Ϫ1.1 (m, 1 H, 6Ј-H), 1.1Ϫ1.35 (m,
3 H, 2Ј,4Ј,6Ј-H), 1.38 (td, J ϭ 12.5, 5.5 Hz, 2 H, 3Ј-H2), 1.47 (dd,
J ϭ 13.8, 8.2 Hz, 1 H, 1Ј-H), 1.70 (dd, 14.1, 5.8 Hz, 1 H, 1Ј-H),
1.85 (s, 3 H, 3-CH3), 6.29 (br. s, 1 H, 4-H), 6.54 (br. s, 1 H, 2-H).
(2S,4S) Isomer: In the same manner as described above, (2S,4S)-26
(26 mg, 0.11 mmol) gave (2S,4S)-27 (21 mg, 81%) as an oil. Its IR
1
Ϫ
13C NMR (125.65 MHz, C6D6): δ ϭ 14.5, 17.1, 18.8, 19.3, 20.5,
and H NMR spectra are identical to those reported for (2R,4R)-
27.
30.0, 37.6, 40.5, 44.3, 116.5, 124.8, 140.5, 146.1, 161.7. Ϫ HREI-
MS [C15H24O2]: calcd. 236.1776; found 236.1776.
(2R,4S) Isomer: In the same manner as described above, (2R,4S)-
26 (35 mg, 0.15 mmol) gave (2R,4S)-27 (24 mg, 68%). Ϫ IR (film): (2S,4R) Isomer: In the same manner as described above, (4S,6R)-
ν˜max ϭ 1745 cmϪ1 (s, CϭO), 1160 (m). Ϫ 1H NMR (300 MHz, 27 (16 mg, 0.062 mmol) gave (2S,4R)-1 (16 mg, quant.) as an oil.
Eur. J. Org. Chem. 2001, 493Ϫ502
501