N. Hanyu et al. / Tetrahedron: Asymmetry 11 (2000) 2971±2979
2977
J=4.6, 5.1 and 12.5 Hz), 1.52±1.56 (1H, m), 1.64±1.67 (1H, m), 1.69±1.77 (1H, m), 2.02±2.11 (1H,
m), 2.54 (1H, d, J=17.2 Hz), 2.61 (1H, d, J=17.2 Hz); C NMR (ꢀ, ppm): 17.42, 22.22, 25.24,
13
^1
25
D
2
CHCl ); m.p.: 134.5±135.5 C; anal. calcd for C H O : C, 67.89; H, 9.50; found: C, 67.94; H,
7.28, 29.14, 39.72, 40.65, 44.35, 49.76, 52.23, 80.43, 180.03; IR: 1690 cm ; ꢁ : 1.9 (c 1.55,
ꢀ
3
12 20
3
9
.53.
.3. Iodine-mediated lactonization of 3-hydroxy acid
Iodine (0.24 g, 0.94 mmol), 3-hydroxy acid (4.7 mmol), and acetonitrile (60 mL) were
3
placed in a 100 mL ¯ask and stirred at an appropriate temperature for 3 hours. After stirring,
the solution was quenched with a 5% aqueous solution of sodium thiosulfate to remove
iodine. After the usual extractive work-up, the crude product was puri®ed by silica gel column
chromatography using hexane and ethyl acetate (8:1) as an eluent to give the corresponding
lactone.
1
Compound 2a: 84% yield (0.76 g, 3.9 mmol); colorless crystal: H NMR (ꢀ, ppm): 1.03 (3H, s),
.07 (3H, s), 1.17 (3H, s), 1.28 (1H, dd, J=10.2 and 1.5 Hz), 1.39±1.48 (1H, m), 1.51±1.63 (2H,
1
m), 1.66±1.76 (1H, m), 1.79±1.82 (1H, m), 1.87±1.92 (1H, m), 2.46 (1H, d, J=17.3 Hz), 2.59 (1H,
d, J=17.3 Hz); 1 C NMR (ꢀ, ppm): 17.81, 22.37, 23.84, 24.45, 24.73, 34.53, 39.69, 44.88, 48.48,
3
^
1
25
D
ꢀ
5
(
5.64, 95.21, 176.48; IR: 1765 cm ; ꢁ : ^95.8 (c 1.24, CHCl ); m.p.: 125.5±126.5 C; HRMS
3
+
FAB) calcd for C H O [M+H] : 195.1385; found: m/z 195.1371.
12
19
2
1
Compound 2b: 91% yield (0.83 g, 4.3 mmol); colorless crystal: H NMR (ꢀ, ppm): 0.95 (3H, s),
.03 (3H, s), 1.20±1.26 (1H, m), 1.34 (3H, s), 1.46 (1H, d, J=13.7 Hz), 1.45±1.51 (1H, m), 1.75±
.81 (1H, m), 1.84±1.90 (2H, m), 2.27 (1H, d, J=17.7 Hz), 2.47 (1H, d, J=17.7 Hz), 2.50 (1H, dt,
1
1
13
J=13.7 and 3.4 Hz); C NMR (ꢀ, ppm): 20.43, 20.79, 24.47, 24.68, 26.43, 30.49, 43.22, 45.00,
^1
25
D
ꢀ
4
(
9.06, 56.34, 92.76, 177.00; IR: 1755 cm ; ꢁ : ^8.1 (c 1.50, CHCl ); m.p.: 183±184 C; HRMS
+
12 19 2
3
FAB) calcd for C H O [M+H] : 195.1385; found: m/z 195.1371.
3
.4. Preparation of hydroxyamide 3
A solution of diethylamine (2.2 g, 30 mmol) in 15 mL of THF was added dropwise to aluminum
ꢀ
chloride (1.3 g, 10 mmol) in 30 mL of THF at 0 C and agitated for 20 min. The reaction mixture
was maintained at the same temperature during the addition. After an additional 30 min, the
cooling bath was removed and a solution of lactone (5.2 mmol) in 15 mL of THF was added
dropwise for 15 min and stirred for the appropriate hours. The reaction mixture was quenched
with water (50 mL) under external cooling, stirred for 30 min and the aqueous layer extracted
three times with diisopropyl ether. The combined organic layers were washed twice with water
and dried over sodium sulfate. After ®ltration and evaporation, the crude product was puri®ed by
silica gel column chromatography using hexane and ethyl acetate (8:1) as an eluent to give the
corresponding hydroxyamide 3.
1
Compound 3a: 81% yield (1.1 g, 4.2 mmol); colorless crystal: H NMR (ꢀ, ppm): 0.93 (3H, s),
1
1
.01 (3H, s), 1.07 (3H, s), 1.12 (3H, t, J=7.1 Hz), 1.19 (3H, t, J=7.1 Hz), 1.08±1.14 (1H, m),
.34±1.43 (2H, m), 1.50±1.64 (2H, m), 1.66±1.71 (1H, m), 2.13±2.21 (1H, m), 2.45 (1H, d, J=14.8
13
Hz), 2.63 (1H, d, J=14.8 Hz), 3.24±3.47 (4H, m), 3.80 (1H, br-s); C NMR (ꢀ, ppm): 13.06,
1
1
4.42, 19.49, 23.75, 24.73, 25.47, 31.87, 33.96, 38.31, 40.46, 42.81, 45.16, 48.33, 54.36, 80.56,
25
^
1
ꢀ
72.97; IR: 3367, 2964, 1620 cm ; ꢁ : ^19.1 (c 1.00, CH CN); m.p.: 122±123 C; anal. calcd for
D
3
C H NO : C, 71.86; H, 10.93; N, 5.24; found: C, 71.92; H, 11.08; N, 5.18.
1
6
29
2