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F. Yuste et al. / Tetrahedron: Asymmetry 14 (2003) 549–554
1H), 4.51 (broad d, 1H, J 8.7), 7.34 and 7.52 (AA‘BB’
system, 4H); 13C NMR (CDCl3, 75 MHz): l 21.4, 23.6,
24.7, 28.3, 39.2, 53.2, 59.6, 69.9, 79.7, 124.0, 130.1,
139.9, 141.5, 156.1; EIMS m/z 369 (5%, M+), 296 (15),
268 (10), 186 (55), 183 (58), 174 (79), 139 (85), 130
(100), 86 (85), 57 (48); HRMS (EI): C19H31NO4S
requires 369.1974. Found: 369.1980.
3.1.4.
(2R,3S)-N-(tert-Butoxycarbonyl)-3-amino-5-
methyl-1-[(4-methylphenyl)sulfenyl]-2-hexanol, 7b. Fol-
lowing the same procedure used for the preparation of
7a, and starting from 0.50 g (1.35 mmol) of 6b, 0.432 g
(90%) of 7b were obtained. The product was purified by
column chromatography. Colorless oil; [h]D −30.2 (c
1.0, CHCl3); IR (CHCl3) wmax: 3443, 2961, 1705, 1498,
1367, 1166 cm−1; H NMR (CDCl3, 300 MHz): l 0.88
1
3.1.2. (2R,3S,Rs)-N-(tert-Butoxycarbonyl)-3-amino-5-
(d, 3H, J 6.6), 0.89 (d, 3H, J 6.6), 1.20–1.35 (m, 2H),
1.43 (s, 9H), 1.50–1.65 (m, 1H), 2.31 (s, 3H), 2.82 (dd,
1H, J 9.9 and 14.0), 3.10 (dd, 1H, J 4.2 and 14.0), 3.50
(broad m, 1H), 3.66 (broad m, 1H), 4.69 (broad d, 1H,
J 9.6), 7.10 and 7.29 (AA‘BB’ system, 4H); 13C NMR
(CDCl3, 75 MHz): l 21.0, 22.1, 23.1, 24.8, 28.4, 40.3,
42.0, 51.5, 70.7, 79.3, 129.9, 130.7, 131.1, 137.2, 156.1;
EIMS m/z 353 (6%, M+), 279 (8), 264 (10), 222 (13),
212 (27), 156 (48), 130 (53), 86 (86), 57 (100).
methyl-1-[(4-methylphenyl)sulfinyl]-2-hexanol, 6b.
A
solution of b-keto sulfoxide 59 (2.8 g, 7.63 mmol, 1
equiv.) in anhydrous THF (5 mL) was added to a
cooled solution of ZnBr2 (0.946 g, 7.63 mmol, 1 equiv.)
in 15 mL of THF at 0°C and the resulting mixture was
stirred at this temperature for 1.5 h. Then the solution
was cooled at −78°C and a 1.5 M solution of DIBAH
in toluene (15 mmol, 1.97 equiv.) was added dropwise.
The reaction mixture was stirred for 1 h at −78°C and
the excess DIBAH was decomposed by adding 20 mL
of MeOH. Once the solution reached room tempera-
ture, the volatiles were removed under vacuum, the
residue was treated with 25 mL of 5% HCl and
extracted with Et2O (2×50 mL). The organic phase was
washed with brine, dried (Na2SO4) and evaporated. The
crude product (2.5 g, de 85%) was purified by crystal-
lization from CH2Cl2/hexane to give 2.11 g (75%) of 6b
as white crystals, mp 115°C; [h]D +111.5 (c 1.0, CHCl3)
de >97%; IR (CHCl3) wmax: 3440, 2961, 1703, 1499,
3.1.5. (S)-1-[(S)-1-(tert-Butoxycarbonylamino)-3-methyl-
butyl]oxirane, 8a. Trimethyloxonium tetrafluoroborate
(2 equiv.) was added to a solution of 7a (0.5 g, 1.42
mmol) in 5 mL of CH2Cl2. The mixture was stirred at
room temperature for 1 h and then a solution of K2CO3
(1.58 mmol) in 3 mL of water was added. The resulting
mixture was vigorously stirred for 24 h. The organic
phase was separated and the aqueous phase was
extracted with CH2Cl2 (3×5 mL). The combined
organic layers were washed with brine, dried and con-
centrated. The residue was purified by column chro-
matography (hexane–ethyl acetate, 8:2) to produce
0.178 g (55%,) of 8a as a white solid, mp 45–47°C; [h]D
−27.6 (c 1.0, CHCl3); IR (CHCl3) wmax: 3443, 2962,
1
1367, 1166 cm−1; H NMR (CDCl3, 300 MHz): l 0.93
(d, 6H, J 6.3), 1.20–1.70 (broad m, 3H), 1.37 (s, 9H),
2.41 (s, 3H), 2.87 (dd, 1H, J 3.6 and 13.5), 2.96 (dd, 1H,
J 8.7 and 13.5), 3.75 (m, 2H, partially interchangeable
with D2O), 4.29 (m, 1H), 4.51 (broad d, 1H, J 9.6), 7.31
and 7.52 (AA‘BB’ system, 4H); 13C NMR (CDCl3, 75
MHz): l 21.4, 22.2, 23.0, 24.7, 28.3, 41.3, 52.7, 60.7,
70.3, 79.2, 123.9, 130.0, 140.4, 141.9, 156.1; EIMS m/z
369 (4%, M+), 296 (10), 268 (9), 186 (40), 174 (100), 139
(53), 130 (84), 86 (90), 57 (82); HRMS (EI):
C19H31NO4S requires 369.1974. Found: 369.1978.
1709, 1500, 1368, 1167 cm−1; H NMR (CDCl3, 300
1
MHz): l 0.91 (d, 3H, J 6.6), 0.94 (d, 3H, J 6.6),
1.35–1.42 (m, 2H), 1.44 (s, 9H), 1.65–1.80 (m, 1H), 2.75
(d, 2H, J 3.8), 2.82–2.86 (m, 1H), 3.50 (broad m, 1H),
4.44 (broad m, 1H); 13C NMR (CDCl3, 75 MHz): l
21.8, 23.3, 24.4, 28.3, 40.8, 46.1, 50.3, 54.5, 79.4, 155.4;
EIMS m/z 229 (not observed, M+), 186 (23), 130 (47),
86 (55), 72 (34), 57 (100).
3.1.3.
(2S,3S)-N-(tert-Butoxycarbonyl)-3-amino-5-
methyl-1-[(4-methylphenyl)sulfenyl]-2-hexanol, 7a. To a
stirred solution of 6a (0.5 g, 1.35 mmol, 1 equiv.) in
EtOH (10 mL) a 15% wt. solution of TiCl3 (2 equiv.) in
20–30% aqueous HCl was added at room temperature.
After 20 min, the solution was cooled in an ice bath,
treated with 10 mL of water and 10 mL of 10%
NaHCO3 and extracted with Et2O (3×15 mL). The
organic phase was washed with brine, dried (Na2SO4)
and evaporated. The residue was crystallized from
CH2Cl2/hexane, to produce 0.41 g (85%) of 7a as a
white solid, mp 97–99°C; [h]D −24.7 (c 1.0, CHCl3); IR
(CHCl3) wma1x: 3442, 3014, 2960, 2930, 1706, 1499, 1368,
1164 cm−1; H NMR (CDCl3, 300 MHz): l 0.90 (d, 3H,
J 6.6), 0.92 (d, 3H, J 6.6), 1.30–1.40 (m, 2H), 1.43 (s,
9H), 1.64 (m, 1H), 2.32 (s, 3H), 2.84 (dd, 1H, J 9.3 and
13.5), 3.08 (dd, 1H, J 3.3 and 13.5), 3.62 (broad m, 1H),
3.72 (broad m, 1H), 4.58 (broad d, 1H, J 7.2), 7.11 and
7.30 (AA‘BB’ system, 4H); 13C NMR (CDCl3, 75
MHz): l 21.0, 21.6, 23.7, 24.7, 28.4, 38.9, 39.4, 52.8,
72.8, 79.9, 129.9, 130.9, 131.0, 136.9, 156.1; EIMS m/z
353 (12%, M+), 222 (25), 212 (45), 156 (70), 130 (92), 86
(100), 57 (93); HRMS (EI): C19H31NO3S requires
353.2025. Found: 353.2034.
3.1.6.
(R)-1-[(S)-1-(tert-Butoxycarbonylamino)-3-
methylbutyl]oxirane, 8b. Following the same procedure
used for the preparation of 8a, and starting from 0.40 g
(1.13 mmol) of 7b, 0.164 g (63%) of 8b were obtained.
The product was purified by column chromatography
(hexane–ethyl acetate, 8:2). Colorless oil; [h]D −43.1 (c
1.0, CHCl3); IR (CHCl3) wmax: 3440, 2961, 1708, 1503,
1368, 1165 cm−1; H NMR (CDCl3, 300 MHz): l 0.95
1
(d, 6H, J 6.6), 1.35–1.55 (m, 2H), 1.43 (s, 9H), 1.65–
1.80 (m, 1H), 2.60 (broad m, 1H), 2.73 (t, 1H, J 4.6),
2.98 (broad m, 1H), 3.97 (broad m, 1H), 4.29 (broad m,
1H); 13C NMR (CDCl3, 75 MHz): l 22.1, 23.0, 24.7,
28.3, 42.3, 44.4, 47.2, 53.9, 79.4, 155.6; EIMS m/z 230
(3%, M++1), 186 (28), 172 (25), 130 (57), 116 (17), 86
(63), 72 (65), 57 (100).
3.1.7. (3R,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-
6-methylheptanenitrile, 9a. A solution of 8a (0.285 g,
1.24 mmol, 1 equiv.) in 2 mL of toluene was dropwise
added to a solution of Et2AlCN (2.4 mmol, 1.93 equiv.)
in 5 mL of toluene cooled at −78°C. The resulting
solution was warmed at −15°C and stirred at this