Diastereoselective Synthesis of Primary â-Amino Alcohols
J . Org. Chem., Vol. 67, No. 11, 2002 3633
1
ter t-Bu t yl N-ter t-Bu t ylt h iom et h yl-N-(1-t r ib u t ylst a n -
n ylh exyl)ca r ba m a te (3e). This compound was prepared from
7e according to the general procedure D in 81% yield: IR (neat)
°C; IR (KBr) 1744 cm-1; H NMR δ 7.40-7.30 (m, 5 Η), 5.56
(d, 1 Η, J ) 8.2), 5.12 (d, 1 H, J ) 14.8), 4.26 (dt, 1 H, J ) 3.8,
8.2), 4.06 (d, 1 H, J ) 14.8), 1.42 (s, 9 H), 1.47-1.24 (m, 2 H),
0.55 (t, 3 H, J ) 7.5); 13C NMR δ 156.9, 134.7, 128.6, 128.4,
126.5, 78.9, 58.3, 43.5, 42.6, 31.2, 20.6, 9.0; EIMS m/z (rel int)
293 (M+, 0.7), 105 (100). Anal. Calcd for C16H23NO2S: C, 65.51;
H, 7.90; N, 4.77. Found: C, 65.54; H, 7.78; N, 4.88. trans-9b
1
1677 cm-1; H NMR δ 4.48 (ΑBq, 2 H, ∆δ ) 0.48, J ) 13.5),
2.89 (t, 1 H, J ) 8.0), 1.8 (m, 2 H), 1.46 (s, 9 H), 1.35 (s, 9 H),
1.5-1.2 (m, 18 H), 0.92-0.71 (m, 18 H); 13C NMR δ 154.5, 79.7,
49.2, 49.0, 42.7, 32.3, 32.8, 31.3, 29.2 (2J ) 19), 28.4, 27.6 (3J
) 57), 22.6, 14.0, 13.7, 10.7 (1J ) 322, 307), 10.0; FABMS m/z
(26% yield): mp 45-49 °C; IR (KBr) 1742 cm-1 1H NMR δ
;
(rel int) 536 (M+ - C4H9, 48), 346 (100). Anal. Calcd for C28H59
-
7.40-7.30 (m, 5 H), 5.12 (d, 1 H, J ) 6.4), 5.10 (d, 1 H, J )
14.9), 4.04 (d, 1 H, J ) 14.9), 3.90 (dt, 1 H, J ) 3.1, 6.4), 1.82-
1.66 (m, 2 H), 1.35 (s, 9 H), 0.98 (t, 3 H, J ) 7.5); 13C NMR δ
156.3, 138.6, 128.7, 125.9, 79.2, 61.4, 43.4, 41.9, 31.1, 23.2, 7.8;
EIMS m/z (rel int) 293 (M+, 0.8), 160 (100). Anal. Calcd for
NO2SSn: C, 56.76; H, 10.04; N, 2.36. Found: C, 56.80; H, 9.82;
N, 2.46.
ter t-Bu tyl N-ter t-Bu tylth iom eth yl-N-(1-cycloh exyl-1-
tr ibu tylsta n n ylm eth yl)ca r ba m a te (3f). This compound was
prepared from 7f according to the general procedure D in 83%
C
16H23NO2S: C, 65.51; H, 7.90; N, 4.77. Found: C, 65.69; H,
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yield: IR (neat) 1681 cm-1; H NMR (200 MHz, C6D6) δ 5.04
7.82; N, 4.88.
(d, 1 H, J ) 12.9), 4.10 (d, 1 H, J ) 12.9), 2.85 (d, 1 H, J ) 9.6,
J SnH ) 49), 2.3 (m, 1 H), 1.84 (m, 16 H), 1.43 (s, 9 H), 1.26 (s,
cis/tr a n s-3-ter t-Bu tylth iom eth yl-5-p h en yl-4-p r op yl-2-
oxa zolid in on e (cis/tr a n s-9c). cis-9c (57% yield): mp 45-
1
9 H), 1.21-0.94 (m, 21 H); H NMR (63 MHz) δ 154.8, 79.6,
47 °C; IR (KBr) 1733 cm-1 1H NMR δ 7.40-7.30 (m, 5 H),
;
56.4, 50.4, 42.4, *40.1, 32.4, *32.3, 31.3, 29.2, *29.1, 28.4, 27.6
(2J ) 59), 26.8, 26.4, 26.2, 13.7, 11.2 (1J ) 320, 306); FABMS
m/z (rel int) 548 (M+ - C4H9, 12). Anal. Calcd for C29H59NO2-
SSn: C, 57.62; H, 9.84; N, 2.32. Found: C, 57.95; H, 9.87, 2.38.
ter t-Bu t yl N-ter t-Bu t ylt h iom et h yl-N-(2-m et h yl-1-t r i-
bu tylsta n n ylp r op yl)ca r ba m a te (3g). This compound was
prepared from 7g according to the general procedure D in 87%
yield: IR (neat) 1681 cm-1; 1H NMR (C6D6) δ 5.02 (d, 1 H, J )
12.9), 4.1 (d, 1 H, J ) 12.9), 2.76 (d, 1 H, J ) 9.2), 2.5 (m, 1
H), 1.8 (m, 12 H), 1.42 (s, 9 H), 1.24, (s, 9 H), 1.49-0.49 (m, 21
H); 13C NMR δ 154.8, 79.6, 57.4, 50.3, 42.5, 31.3, 31.2, 29.3
(2J ) 19), 28.4, 27.6 (3J ) 59), *21.9, *21.7, 21.6, 21.4, *21.1,
13.7, 11.3 (1J ) 321); FABMS m/z (rel int) 508 (M+ - C4H9,
52), 318 (100). Anal. Calcd for C26H55NO2SSn: C, 55.33; H,
9.82; N, 2.48. Found: C, 55.19; H, 9.77; N, 2.39.
5.45 (d, 1 H, J ) 8.2), 5.10 (d, 1 H, J ) 14.8), 4.30 (dt, 1 H, J
) 8.2, 3.7), 4.10 (d, 1 H, J ) 14.8), 1.42 (s, 9 H), 1.37-1.00 (m,
2 H), 1.2-0.8 (m, 2 H, CH3CH2CH2), 0.64 (t, 3 H, J ) 7.0, CH3-
CH2CH2); 13C NMR (63 MHz) δ 156.7, 134.7, 128.5, 128.2,
126.4, 78.9, 56.9, 43.3, 42.5, 31.1, 29.7, 18.0, 13.8; EIMS m/z
(rel int) 307 (M+, 0.4), 91 (100). Anal. Calcd for C17H25NO2S:
C, 66.42; H, 8.20; N, 4.55. Found: C, 66.67; H, 8.23; N, 4.67.
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trans-9c (29% yield): mp 63-66 °C; IR (KBr) 1741 cm-1; H
NMR δ 7.40-7.30 (m, 5 H), 5.10 (d, 1 H, J ) 6.1), 5.10 (d, 1 H,
J ) 14.8), 4.10 (d, 1 H, J ) 14.8), 4.0 (m, 1 H), 1.84-1.71 (m,
2 H), 1.68-1.40 (m, 2 H), 1.34 (s, 9 H), 0.96 (t, 3 H, J ) 7.2);
13C NMR (63 MHz) δ 156.2, 138.5, 128.7, 126.0, 79.9, 60.4,
43.3, 41.9, 33.0, 31.1, 17.2, 14.0; EIMS m/z (rel int) 307 (M+,
0.4), 132 (100). Anal. Calcd for C17H25NO2S: C, 66.42; H, 8.20;
N, 4.55. Found: C, 66.54; H, 8.25; N, 4.56.
Gen er a l P r oced u r e E: P r ep a r a tion of Oxa zolid in on es
9. To a cooled (-78 °C) 0.15 M solution of the R-aminoorga-
nostannane 3 in THF was added n-BuLi (1.5 equiv) slowly,
and the solution was stirred for 15 min. The appropriate
aldehyde (2.0 equiv) was added, and the mixture was stirred
for 15 min and quenched at -78 °C with saturated NH4Cl.
The mixture was diluted with Et2O, washed with water, dried
(MgSO4), filtered through Celite, and concentrated in vacuo
to give â-amino alcohols, which were used without purification
in most cases. To a 0.1 M solution of â-amino alcohol in THF
was added NaH (2 equiv), and the mixture was stirred for 30-
60 min, quenched with water, diluted with Et2O, and washed
with water. The organic layer was dried (MgSO4), filtered
through Celite, and concentrated in vacuo. The ratios of
diastereomers in the crude products are recorded in Table 1.
The resulting oils were purified by flash chromatography (100
g silica/g substrate; 5:1 hexane/Et2O) to give oxazolidinones
as colorless oils or white solids. Combined yields are reported
in Table 1; specific isolated yields are noted below.
cis/tr a n s-4-Bu tyl-3-ter t-bu tylth iom eth yl-5-p h en yl-2-ox-
a zolid in on e (cis/tr a n s-9d ). cis-9d (55% yield): mp 48-50
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°C; IR (KBr) 1730 cm-1; H NMR δ 7.41-7.29 (m, 5 H), 5.56
(d, 1 H, J ) 8.2), 5.10 (d, 1 H, J ) 14.9), 4.30 (dt, 1 H, J ) 3.7,
8.2), 4.06 (d, 1 H, J ) 14.9), 1.42 (s, 9 H), 1.44-0.85 (m, 6 H),
0.64 (t, 3 H, J ) 7.3); 13C NMR δ 156.8, 134.8, 128.6, 128.3,
126.6, 79.0, 57.2, 43.5, 42.6, 31.2, 27.2, 26.9, 22.4, 13.4; EIMS
m/z (rel int) 321 (M+, 0.2), 132 (100). Anal. Calcd for C18H27
-
NO2S: C, 67.26; H, 8.47; N, 4.43. Found: C, 67.33; H, 8.45;
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N, 4.39. trans-9d (24% yield): IR (neat) 1753 cm-1; H NMR
δ 7.43-7.27 (m, 5 H), 5.11(d, 1 H, J ) 5.8), 5.07 (d, 1H, J )
14.9), 4.05 (d, 1 H, J ) 14.9), 4.04-3.97 (m, 1 H), 1.83-1.74
(m, 1 H), 1.69-1.57 (m, 1 H), 1.34 (s, 9 H), 1.46-1.20 (m, 4
H), 0.91 (t, 3 H, J ) 6.8); 13C NMR δ 156.3, 138.6, 128.7, 125.9,
79.9, 60.6, 43.4, 42.0, 31.1, 30.5, 25.9, 22.5, 13.8; EIMS m/z
(rel int) 321 (M+, 0.4), 132 (100). Anal. Calcd for C18H27NO2S:
C, 67.26; H, 8.47; N, 4.43. Found: C, 67.06; H, 8.30; N, 4.52.
cis/tr a n s-3-ter t-Bu t ylt h iom et h yl-4-p en t yl-5-p h en yl-2-
oxa zolid in on e (cis/tr a n s-9e). cis-9e (51% yield): IR (neat)
1
For the systems where R ) n-butyl or n-pentyl, it was easier
to separate the two diastereomers as the protected â-amino
alcohols (i.e., before cyclization). However the syn diastereomer
was still contaminated with 1-phenyl-1-pentanol, which was
then removed after cyclization.
1754 cm-1; H NMR δ 7.36-7.40 (m, 5 H), 5.56 (d, 1 Η, J )
8.2), 5.10 (d, 1 H, J ) 14.9), 4.30 (dt, 1 H, J ) 8.2, 3.6), 4.06
(d, 1 H, J ) 14.9), 1.42 (s, 9 H), 1.20-0.84 (m, 8 H), 0.71 (t, 3
H, J ) 6.7); 13C NMR δ 156.9, 134.7, 128.6, 128.4, 126.6, 79.1,
57.5, 43.5, 42.6, 31.5, 31.3, 27.6, 24.3; EIMS m/z (rel int) 335
(M+, 0.1), 132 (100). Anal. Calcd for C19H29NO2S: C, 68.03; H,
8.71; N, 4.17. Found: C, 67.89; H, 8.67; N, 4.18. trans-9e (24%
cis/tr a n s-3-ter t-Bu tylth iom eth yl-4-m eth yl-5-p h en yl-2-
oxa zolid in on e (cis/tr a n s-9a ). cis-9a (65% yield): mp 98-
1
99 °C; IR (KBr) 1734 cm-1
;
1H NMR δ 7.43-7.26 (m, 5 H),
yield): IR (neat) 1748 cm-1; H NMR δ 7.40-7.30 (m, 5 H),
5.58 (d, 1 H, J ) 8.4), 5.07 (d, 1 H, J ) 14.7), 4.40 (quintet, 1
H, J ) 6.6), 4.01 (d, 1 H, J ) 14.7), 1.42 (s, 9 H), 0.78 (d, 3 H,
J ) 6.6); 13C NMR δ 156.4, 134.5,128.4, 126, 78.6, 53.0, 43.4,
42.1, 31.2, 13.9; EIMS m/z (rel int) 279 (M+, 1), 146 (94), 105
(100). Anal. Calcd for C15H21NO2S: C, 64.50; H, 7.58; N, 5.01.
Found: C, 64.67; H, 7.72; N, 5.02. trans-9a (25% yield): mp
60-62 °C; IR (KBr) 1750 cm-1; 1H NMR δ 7.40-7.30 (m, 5 H),
5.06 (d, 1 H, J ) 14.9), 4.94 (d, 1 H, J ) 8.1), 4.1 (d, 1 H, J )
14.9, CH2S), 3.98 (quintet, 1 H, J ) 6.2), 1.37 (m, 12 H); 13C
NMR δ 156.3, 137.4, 128.9, 128.8, 125.9, 82.6, 57.3, 43.3, 41.9,
31.1, 16.8; EIMS m/z (rel int) 279 (M+, 0.8), 146 (100). Anal.
Calcd for C15H21NO2S: C, 64.50; H, 7.58; N, 5.01. Found: C,
64.47; H, 7.67; N, 4.88.
5.10 (d, 1 H, J ) 5.8), 5.07 (d, 1 H, J ) 14.4), 4.06 (d, 1 H, J
) 14.4), 3.90 (m, 1 H), 1.70-1.40 (m, 2 H), 1.35 (s, 9 H), 1.30-
0.94 (m, 6 H), 0.88 (t, 3 H, J ) 6.4); 13C NMR δ 156.3, 138.6,
126.6, 126.0, 79.0, 60.7, 43.4, 42.1, 31.6, 31.2, 27.6, 23.4, 2.6,
13.6; EIMS m/z (rel int) 335 (M+, 0.3), 132 (100). Anal. Calcd
for C19H29NO2S: C, 68.03; H, 8.71; N, 4.17. Found: C, 68.14;
H, 8.61; N, 3.96.
cis-3-ter t-Bu tylth iom eth yl-4-cycloh exyl-5-p h en yl-2-ox-
a zolid in on e (cis-9f). This compound was prepared from 3f
according to the general procedure E except that 1.3 equiv of
benzaldehyde was used (40% yield): mp 109-110 °C; IR (KBr)
1
1738 cm-1; H NMR δ 7.40-7.27 (m, 5 H), 5.60 (d, 1 H, J )
8.0), 5.21 (d, 1 H, J ) 14.9), 4.2 (m, 1 H), 4.15 (d, 1 H, J )
14.9), 1.60-1.45 (m, 5 H), 1.42 (s, 9 H), 1.26-0.78 (m, 6 H,);
13C NMR δ 157.1, 134.7, 128.3, 125.9, 80.1, 61.5, 44.5, 43.6,
cis/tr a n s-3-ter t-Bu tylth iom eth yl-4-eth yl-5-p h en yl-2-ox-
a zolid in on e (cis/tr a n s-9b). cis-9b (51% yield): mp 43-45