1504
D. OGURO and H. WATANABE
and 13C-NMR at 100 MHz). Chemical shifts are reported in parts per
million (ꢀ) relative to internal chloroform (1H, CHCl3 at ꢀ 7.26; 13C,
CDCl3 at ꢀ 77.0). Optical rotation data were measured by a Jasco P-
1030 polarimeter, and HRMS data were recorded with a Jeol JMS-
700T (FAB) or Jeol JMS-T100LC AccuTOF (ESI) instrument. GCMS
analyses were carried out with an Agilent 6890N gas chromatograph
(30 m TC-1701 capillary column, 0.25 mm ID, 0.25 mm film) equipped
with an Agilent 5973 mass selective detector. The enantiomeric excess
was determined by gas chromatography, using a Chiramixꢀ chiral
separating column (60 m, 0.25 mm ID).19) Analytical thin-layer
chromatography (TLC) was carried out by using 0.25 mm Merck
silica gel 60 F254 precoated glass-backed plates. Compounds were
visualized by ultraviolet light (254 nm), iodine vapor or phosphomo-
lybdic acid spray reagent. Column chromatography was performed on
Merck silica gel 60 or Kanto Chemical silica gel 60N (neutral).
2958, 1716, 1599, 1304, 1265, 1198, 1140, 1006, 866; 1H-NMR
(400 MHz, CDCl3) ꢀ: 0.92 (t, 3H, J ¼ 7:1 Hz), 1.31–1.50 (m, 4H),
1.78–1.83 (m, 2H), 2.45 (d, 1H, J ¼ 2:2 Hz), 5.43 (dt, 1H, J ¼ 2:2,
6.7 Hz), 5.51 (d, 1H, J ¼ 9:6 Hz), 5.63 (d, 1H, J ¼ 17:0 Hz), 5.92 (d,
1H, J ¼ 15:1 Hz), 6.46 (dt, 1H, J ¼ 17:0, 10.6 Hz), 7.30 (dd, 1H,
J ¼ 15:6, 11.0 Hz); 13C-NMR (100 MHz, CDCl3) ꢀ: 13.87, 22.19,
26.99, 34.34, 63.76, 73.39, 81.35, 121.53, 126.06, 134.62, 145.53,
165.68; HRMS (ESI): calcd. for C12H17O2 ðM þ HÞþ, 193.1229;
found, 193.1229.
(S)-1-Ethynylpentyl 2,4-pentadienoate [(S)-(ꢀ)-5]. In the same
manner as that described for the synthesis of (ꢁ)-5, (S)-(ꢀ)-4 (0.30 g,
2.67 mmol) afforded ester (S)-(ꢀ)-5 (0.41 g, 78%) as a colorless oil.
20
½ꢁꢃD ꢀ62:9 (c 1.02, CHCl3); HRMS (ESI): calcd. for C12H16NaO2
ðM þ NaÞþ, 215.1048; found, 215.1050. All other data were identical
with those for (ꢁ)-5.
(S)-1-Heptyn-3-ol [(S)-(ꢀ)-4] and (R)-1-heptyn-3-ol [(R)-(þ)-4]. A
mixture of (ꢁ)-4 (2.00 g, 17.8 mmol), CAL-B (Novozym 435, 0.18 g),
diisopropyl ether (18 mL) and vinyl acetate (3.10 g, 35.6 mmol) was
stirred at room temperature for 5 h. After filtration through a Celiteꢀ
pad, the filtrate was concentrated in vacuo. The resulting residue was
chromatographed on silica gel (150 g). Elution with n-hexane/ethyl
acetate (50/1–5/1) gave acetate (S)-(ꢀ)-6 (1.16 g, 40%, 90.6% ee) as a
product and (R)-(þ)-4 (0.96 g, 44%, 80.7% ee) as a residual substrate.
(R)-1-Ethynylpentyl 2,4-pentadienoate [(R)-(þ)-5]. In the same
manner as that described for the synthesis of (ꢁ)-5, (R)-(þ)-4 (0.30 g,
2.67 mmol) afforded ester (R)-(þ)-5 (0.43 g, 83%) as a colorless oil.
20
½ꢁꢃD þ60:3 (c 1.04, CHCl3); HRMS (ESI): calcd. for C12H17O2
ðM þ HÞþ, 193.1229; found, 193.1228. All other data were identical
with those for (ꢁ)-5.
(ꢁ)-Sedanenolide [(ꢁ)-1] and (ꢁ)-3-butylphthalide [(ꢁ)-3]. A
mixture of (ꢁ)-5 (0.40 g, 2.0 mmol), toluene (40 mL) and a catalytic
amount of 4,4-thiobis(6-t-butyl-m-cresol) was heated at 220 ꢂC for 9 h
in an autoclave under argon. The reaction mixture was concentrated
in vacuo. The resulting residue was chromatographed on silica gel
(15 g) and eluted with n-hexane/ethyl acetate (20/1–10/1) to give a
mixture of (ꢁ)-1 and (ꢁ)-3 (0.27 g), together with a small amount of
impurities, as a pale yellow oil. Further purification by Lobarꢀ column
chromatography [Merck LiChroprepꢀ Si 60 (40–63 mm), pre-packed
column size A (240–10), n-hexane/ethyl acetate (20/1)] gave (ꢁ)-1
(0.19 g, 50%) and (ꢁ)-3 (49 mg, 13%), both as colorless oils. (ꢁ)-1. IR
(film) cmꢀ1: 2932, 1750, 1655, 1435, 1335, 1273, 1045, 1006, 963,
715; 1H-NMR (400 MHz, CDCl3) ꢀ: 0.90 (t, 3H, J ¼ 7:1 Hz), 1.29–
1.44 (m, 4H), 1.53 (m, 1H), 1.88 (m, 1H), 2.43–2.52 (m, 4H), 4.92
(dd, 1H, J ¼ 7:8, 3.7 Hz), 5.91 (m, 1H), 6.20 (d, 1H, J ¼ 9:6 Hz);
13C-NMR (100 MHz, CDCl3) ꢀ: 13.83, 20.77, 22.27, 22.42, 26.70,
31.88, 82.48, 116.87, 124.49, 128.28, 161.37, 171.24; GCMS: 192 (13,
Mþ), 135 (4), 107 (100), 91 (4), 85 (8), 77 (27), 57 (7), 51 (6), 41 (4);
HRMS (ESI): calcd. for C12H16NaO2 ðM þ NaÞþ, 215.1048; found,
215.1046. (ꢁ)-3. IR (film) cmꢀ1: 2956, 1760, 1347, 1285, 1212, 1061,
984, 743, 708, 694; 1H-NMR (400 MHz, CDCl3) ꢀ: 0.90 (t, J ¼ 7:1 Hz,
3H), 1.30–1.50 (m, 4H), 1.76 (m, 1H), 2.05 (m, 1H), 5.47 (dd, J ¼ 8:0,
3.9 Hz, 1H), 7.43 (d, J ¼ 7:6 Hz, 1H), 7.52 (t, J ¼ 7:6 Hz, 1H), 7.67
(t, J ¼ 7:6 Hz, 1H), 7.89 (d, J ¼ 7:6 Hz, 1H); 13C-NMR (100 MHz,
CDCl3) ꢀ: 13.83, 22.40, 26.85, 34.41, 81.42, 121.68, 125.69, 126.14,
128.99, 133.90, 150.10, 170.68; GCMS: 190 (2, Mþ), 133 (100), 105
(27), 77 (12), 51 (5); HRMS (ESI): calcd. for C12H14NaO2 ðM þ NaÞþ,
213.0892; found, 213.0902.
20
(S)-(ꢀ)-6. ½ꢁꢃD ꢀ83:7 (c 1.08, CHCl3); IR (film) cmꢀ1: 3293, 2958,
2934, 2866, 1743, 1468, 1372, 1233, 1049, 1020; 1H-NMR (400 MHz,
CDCl3) ꢀ: 0.91 (t, J ¼ 7:2 Hz, 3H), 1.20–1.46 (m, 4H), 1.84–1.74 (m,
2H), 2.08 (s, 3H), 2.44 (d, J ¼ 2:3 Hz, 1H), 5.33 (dt, J ¼ 2:3, 6.7 Hz,
1H); 13C-NMR (100 MHz, CDCl3) ꢀ: 13.87, 20.97, 22.17, 26.97, 34.25,
63.77, 73.34, 81.31, 169.94; HRMS (ESI): calcd. for C9H14NaO2
ðM þ NaÞþ, 177.0891; found, 177.0881.
A mixture of (S)-(ꢀ)-6 (1.00 g, 6.2 mmol), CAL-B (Novozym 435,
0.10 g) and a 0.1 M phosphate buffer solution (pH 7.0, 20 mL) was
stirred at room temperature for 3.5 h. After filtration through Celiteꢀ,
the filtrate was extracted with diethyl ether, and the resulting extract
was successively washed with an aqueous sodium bicarbonate solution
and brine, dried over magnesium sulfate and concentrated in vacuo.
The residue was chromatographed on silica gel (30 g), elution with
n-hexane/ethyl acetate (50/1–5/1) giving (S)-(ꢀ)-4 (0.49 g, 67%,
20
>99:9% ee). ½ꢁꢃD ꢀ9:74 (c 1.03, CHCl3); IR (film) cmꢀ1: 3310, 2958,
2935, 2863, 1467, 1381, 1051, 1020, 656, 629; 1H-NMR (400 MHz,
CDCl3) ꢀ: 0.92 (t, J ¼ 7:2 Hz, 3H), 1.31–1.49 (m, 4H), 1.65–1.78 (m,
2H), 1.87 (s, 1H), 2.46 (d, J ¼ 2:0 Hz, 1H), 4.37 (dt, J ¼ 2:0, 6.5 Hz,
1H); 13C-NMR (100 MHz, CDCl3) ꢀ: 13.95, 22.30, 27.12, 37.32, 62.30,
72.80, 85.00; HRMS (ESI): calcd. for C7H12NaO ðM þ NaÞþ,
135.0786; found, 135.0777.
A mixture of (R)-(þ)-4 (0.84 g, 6.9 mmol, 80.7% ee), CAL-B
(Novozym 435, 0.07 g), diisopropyl ether (7 mL) and vinyl acetate
(1.20 g, 13.8 mmol) was stirred at room temperature for 6 h. After
filtration through a Celiteꢀ pad, the filtrate was concentrated in vacuo.
The resulting residue was chromatographed on silica gel (35 g), elution
with n-hexane/ethyl acetate (50/1–5/1) giving residual (R)-(þ)-4
20
(0.55 g, 68%, 97.4% ee) as a colorless oil. ½ꢁꢃD þ9:34 (c 1.05,
(S)-(ꢀ)-Sedanenolide [(S)-(ꢀ)-1] and (S)-(ꢀ)-3-butylphthalide
[(S)-(ꢀ)-3]. In the same manner as that described for the synthesis
of the racemates, (S)-(ꢀ)-5 (0.35 g, 1.80 mmol) afforded (S)-(ꢀ)-1
(0.15 g, 43%, 98.0% ee) and (S)-(ꢀ)-3 (41 mg, 12%, 99.6% ee), both
CHCl3); HRMS (ESI): calcd. for C7H12NaO ðM þ NaÞþ, 135.0786;
found, 135.0775. All other data were identical with those for (S)-(ꢀ)-4.
20
1-Ethynylpentyl 2,4-pentadienoate [(ꢁ)-5]. To a mixture of 2,4-
pentadienoic acid (0.60 g, 6.1 mmol) and toluene (3 mL) was added a
mixture of benzoyl chloride (0.86 g, 6.1 mmol), triethylamine (0.62 g,
6.1 mmol) and toluene (3 mL) at 10 ꢂC. After being stirred at room
temperature for 0.5 h, the reaction mixture was filtered through a
Celiteꢀ pad. The filtrate was concentrated in vacuo to give a crude
anhydride (1.36 g).
as colorless oils. (S)-(ꢀ)-1. ½ꢁꢃD ꢀ134 (c 1.04, CHCl3); HRMS (ESI):
calcd. for C12H16NaO2 ðM þ NaÞþ, 215.1048; found, 215.1064. All
20
other data were identical with those for (ꢁ)-1. (S)-(ꢀ)-3. ½ꢁꢃD ꢀ69:1
(c 1.04, CHCl3); HRMS (ESI): calcd. for C12H16NaO2 ðM þ NaÞþ,
213.0892; found, 213.0895. All other data were identical with those
for (ꢁ)-3.
To a mixture of this anhydride (1.36 g) and THF (3 mL) was added
dropwise a mixture of (ꢁ)-4 (0.30 g, 2.7 mmol), triethylamine (0.27 g,
2.7 mmol), a catalytic amount of N,N-dimethylaminopyridine and THF
(3 mL) at 10 ꢂC. After being stirred at room temperature for 0.5 h, the
reaction mixture was diluted with diethyl ether, and successively
washed with diluted aqueous hydrochloric acid, a saturated aqueous
sodium bicarbonate solution and brine, dried over anhydrous magne-
sium sulfate and concentrated in vacuo. The residue was chromato-
graphed on silica gel (45 g) and eluted with n-hexane/ethyl acetate
(R)-(þ)-Sedanenolide [(R)-(þ)-1] and (R)-(þ)-3-butylphthalide
[(R)-(þ)-3]. In the same manner as that described for the synthesis
of the racemates, (R)-(þ)-5 (0.35 g, 1.80 mmol) afforded (R)-(þ)-1
(0.17 g, 50%, 96.2% ee) and (R)-(þ)-3 (37 mg, 11%, 97.0% ee), both
20
as colorless oils. (R)-(þ)-1. ½ꢁꢃD þ121 (c 1.02, CHCl3); HRMS (ESI):
calcd. for C12H17O2 ðM þ HÞþ, 193.1229; found, 193.1235. All other
20
data were identical with those for (ꢁ)-1. (R)-(þ)-3. ½ꢁꢃD þ64:8
(c 1.02, CHCl3); HRMS (ESI): calcd. for C12H16NaO2 ðM þ NaÞþ,
213.0892; found, 213.0910. All other data were identical with those
for (ꢁ)-3.
(50/1) to give (ꢁ)-5 (0.48 g, 94%) as a colorless oil. IR (film) cmꢀ1
: