Tang and Ellman
1
by H NMR. Pure 4i was obtained in 81% yield after column
for C15H23NO3S: C, 60.58; H, 7.79; N, 4.71. Found: C, 60.46;
H, 7.52; N, 4.71.
chromatography with 30% EtOAc/hexanes to 75% EtOAc/
hexanes as eluent: [R]23 -7.3 (c 1.0, CHCl3); IR 1048, 1736,
D
(RS,2S,3R)-(-)-2-Ben zyl-3-(2-m eth ylp r op a n e-2-su lfin yl-
a m in o)p en ta n oic Acid Meth yl Ester (4m ). The general
procedure was followed using 0.500 g (3.10 mmol) of imine 3i,
0.894 mL (6.82 mmol) of i-Pr2NH, 3.26 mL (6.51 mmol) of
n-BuLi, 1.02 g (6.20 mmol) of hydrocinnamic acid methyl ester,
and 3.11 mL (13.0 mmol) of ClTi(Oi-Pr)3. Diastereoselectivity
was determined via HPLC analysis of the filtered, crude
reaction mixture (90:10:0:0 dr, Si column, 97:3 hexanes/
i-PrOH; 1 mL/min; 215 nm; major diastereomer, tR ) 20.3 min;
minor diastereomers, tR ) 14.2, 15.9, 17.5). An authentic
mixture of diastereomers was prepared by the nonstereose-
lective addition of the corresponding lithium enolate. The
HPLC peaks corresponding to each of the minor diastereomers
were confirmed by 1H NMR. Pure 4m was obtained in 67%
yield after column chromatography with 40% EtOAc/hexanes
2955 cm-1; H NMR (400 MHz) δ 0.78 (d, 3H, J ) 6.7), 0.81
1
(d, 3H, J ) 6.7), 1.07 (d, 3H, J ) 7.2), 1.13 (s, 9H), 1.15-1.24
(m, 2H), 1.62-1.69 (m, 1H), 2.91-3.01 (m, 1H), 3.24-3.39 (m,
1H), 3.61 (s, 3H), 4.22 (d, 1H, J ) 9.3); 13C NMR (100 MHz) δ
13.1, 21.0, 22.6, 23.3, 24.3, 40.4, 44.3, 51.5, 55.8, 57.5, 174.8.
Anal. Calcd for C13H27NO3S: C, 56.28; H, 9.81; N, 5.05.
Found: C, 56.05; H, 9.82; N, 4.94.
(RS,2S,3R)-(-)-2,5-Dim eth yl-3-(2-m eth ylpr opan e-2-su lfi-
n yla m in o)h exa n oic Acid ter t-Bu tyl Ester (4j). The general
procedure was followed using 0.500 g (2.64 mmol) of imine 3c,
0.762 mL (5.81 mmol) of i-Pr2NH, 2.77 mL (5.55 mmol) of
n-BuLi, 0.795 mL (5.28 mmol) of tert-butyl propionate, and
2.65 mL (11.09 mmol) of ClTi(Oi-Pr)3. Diastereoselectivity was
determined via HPLC analysis of the filtered, crude reaction
mixture (59:19:17:5 dr, Si column, 97:3 hexanes/i-PrOH; 1 mL/
min; 215 nm; major diastereomer, tR ) 26.8 min; minor
diastereomers, tR ) 19.7, 22.0, 24.9). An authentic mixture of
diastereomers was prepared by the nonstereoselective addition
of the corresponding lithium enolate. The HPLC peaks corre-
sponding to each of the minor diastereomers were confirmed
to 75% EtOAc/hexanes as eluent: [R]23 -52.4 (c 1.0, CHCl3);
D
IR 1049, 1733, 2977 cm-1; 1H NMR (500 MHz) δ 0.92 (m, 3H),
1.21 (s, 9H), 1.37-1.40 (m, 1H), 1.62-1.68 (m, 1H), 2.79 (dd,
1H, J ) 14, 7.3), 3.09 (dd, 1H, J ) 14, 8.4), 3.19-3.23 (m, 1H),
3.30-3.35 (m, 1H), 3.63 (s, 3H), 4.20 (d, 1H, J ) 8.4), 7.17-
7.28 (m, 5H); 13C NMR (125 MHz) δ 10.8, 22.7, 24.7, 34.4, 51.5,
51.8, 56.0, 59.2, 126.4, 128.5, 128.7, 138.6, 174.0. Anal. Calcd
for C17H27NO3S: C, 62.74; H, 8.36; N, 4.30. Found: C, 63.13;
H, 8.71; N, 4.38. X-ray quality crystals were obtained from
slow evaporation of solvent (Et2O).
1
by H NMR. Pure 4j was obtained in 87% yield after column
chromatography with 30% EtOAc/hexanes to 75% EtOAc/
hexanes as eluent: [R]23 -6.4 (c 1.0, CHCl3); IR 1049, 1733
D
cm-1; 1H NMR (400 MHz) δ 0.79 (d, 3H, J ) 6.7), 0.83 (d, 3H,
J ) 6.7), 1.10 (d, 3H, J ) 7.2), 1.14 (s, 9H), 1.19-1.25 (m, 2H),
1.30 (s, 9H), 1.63-1.69 (m, 1H), 2.97-3.04 (m, 1H), 3.26-3.35
(m, 1H), 4.23 (d, 1H, J ) 9.3); 13C NMR (100 MHz) δ 13.3,
21.0, 22.6, 23.4, 24.3, 29.9, 40.3, 44.3, 55.9, 57.6, 68.3, 174.7.
Anal. Calcd for C16H33NO3S: C, 60.15; H, 10.41; N, 4.38.
Found: C, 60.19; H, 10.37; N, 4.24.
(RS,2S,3R)-(-)-2-Ben zyl-3-(2-m eth ylp r op a n e-2-su lfin yl-
a m in o)p en ta n oic Acid 4-Meth oxyben zyl Ester (4n ). The
general procedure was followed using 0.500 g (3.10 mmol) of
imine 3i, 0.894 mL (6.82 mmol) of i-Pr2NH, 3.26 mL (6.51
mmol) of n-BuLi, 1.68 g (6.20 mmol) of hydrocinnamic acid
4-methoxybenzyl ester, and 3.11 mL (13.0 mmol) of ClTi(Oi-
1
(RS,2S,3R)-(-)-2,5-Dim eth yl-3-(2-m eth ylpr opan e-2-su lfi-
n yla m in o)h exa n oic Acid 4-Met h oxyb en zyl E st er (4k ).
The general procedure was followed using 0.500 g (2.64 mmol)
of imine 3c, 0.762 mL (5.81 mmol) of i-Pr2NH, 2.77 mL (5.55
mmol) of n-BuLi, 1.026 g (5.28 mmol) of 4-methoxybenzyl
propionate, and 2.65 mL (11.09 mmol) of ClTi(Oi-Pr)3. Dias-
tereoselectivity was determined by NMR integration of the
crude reaction mixture (88:12 dr, undetectable amounts of the
other two diastereomers). An authentic mixture of diastereo-
mers was prepared by the nonstereoselective addition of the
corresponding lithium enolate. Pure 4k was obtained in 85%
yield after column chromatography with 30% EtOAc/hexanes
Pr)3. Diastereoselectivity was determined by H NMR integra-
tion (93:7 dr, undetectable amounts of other two diastereo-
mers). An authentic mixture of diastereomers was prepared
by the nonstereoselective addition of the corresponding lithium
enolate. Pure 4n was obtained in 70% yield after column
chromatography with 40% EtOAc/hexanes to 75% EtOAc/
hexanes as eluent: [R]23D -31.4 (c 1.0, CHCl3); IR 1036, 1162,
1
1602, 1732 cm-1 ; H NMR (400 MHz) δ 0.89 (t, 3H, J ) 7.3),
1.13 (s, 9H), 1.30-1.36 (m, 1H), 1.60-1.67 (m, 1H), 2.80 (dd,
1H, J ) 14, 7.1), 3.11 (dd, 1H, J ) 14, 8.6), 3.19-3.23 (m, 1H),
3.32-3.37 (m, 1H), 3.80 (s, 3H), 4.19 (d, 1H, J ) 7.4), 4.94 (d,
1H, J ) 12), 5.09 (d, 1H, J ) 12), 6.86 (d, 2H, J ) 8.7), 7.20
(m, 5H), 7.26 (d, 2H, J ) 8.2); 13C NMR (100 MHz) δ 10.8,
22.6, 24.7, 34.3, 51.6, 55.2, 55.9, 59.3, 66.4, 113.9, 126.3, 127.4,
to 75% EtOAc/hexanes as eluent: [R]23 -7.4 (c 1.0, CHCl3);
D
IR 1031, 1614, 1710, 2956 cm-1; H NMR (400 MHz) δ 0.82
1
(d, 3H, J ) 6.6), 0.85 (d, 3H, J ) 6.7), 1.14 (s, 9H), 1.16 (d,
3H, J ) 7.2), 1.20-1.35 (m, 2H), 1.64-1.71 (m, 1H), 3.05-
3.09 (m, 1H), 3.29-3.36 (m, 1H), 3.80 (s, 3H), 4.26 (d, 1H, J )
9.4), 5.01 (d, 1H, J ) 12), 5.14 (d, 1H, J ) 12), 6.88 (d, 2H, J
) 8.7), 7.29 (d, 2H, J ) 8.7); 13C NMR (100 MHz) δ 13.4, 21.0,
22.6, 23.4, 24.3, 40.3, 44.7, 55.2, 55.9, 57.9, 66.2, 113.9, 127.7,
130.2, 159.6, 174.2. Anal. Calcd for C20H33NO4S: C, 62.63; H,
8.67; N, 3.65. Found: C, 62.28; H, 8.88; N, 3.75.
128.5, 128.8, 130.2, 138.5, 159.7, 173.3. Anal. Calcd for C24H33-
NO4S: C, 66.79; H, 7.71; N, 3.25. Found: C, 66.73; H, 7.68;
N, 3.35.
(RS,2S,3R)-(-)-2-(4-Meth oxyben zyl)-3-(2-m eth ylpr opan e-
2-su lfin yla m in o)bu tyr ic Acid Meth yl Ester (4o). The
general procedure was followed using 0.500 g (3.40 mmol) of
imine 3a , 0.979 mL (7.47 mmol) of i-Pr2NH, 3.57 mL (7.13
mmol) of n-BuLi, 1.32 g (6.79 mmol) of 3-(4-methoxyphenyl)-
propionic acid methyl ester, and 3.41 mL (14.3 mmol) of ClTi-
(Oi-Pr)3. Diastereoselectivity was determined via HPLC analy-
sis of the filtered, crude reaction mixture (83:17:0:0 dr, Si
column, 90:10 hexanes/i-PrOH; 1 mL/min; 215 nm; major
diastereomer, tR ) 26.8 min; minor diastereomers, tR ) 19.7,
22.0, 24.9). An authentic mixture of diastereomers was pre-
pared by the nonstereoselective addition of the corresponding
lithium enolate. The HPLC peaks corresponding to each of the
minor diastereomers were confirmed by mass spectrometry.
Pure 4o was obtained in 65% yield after column chromatog-
raphy with 40% EtOAc/hexanes to 75% EtOAc/hexanes as
(RS,2S,3S)-(-)-2-Meth yl-3-(2-m eth ylp r op a n e-2-su lfin yl-
a m in o)-3-p h en ylp r op ion ic Acid Meth yl Ester (4l). The
general procedure was followed using 0.500 g (2.39 mmol) of
imine 3d , 0.689 mL (5.26 mmol) of i-Pr2NH, 2.51 mL (5.02
mmol) of n-BuLi, 0.460 mL (4.78 mmol) of methyl propionate,
and 2.40 mL (11.9 mmol) of ClTi(Oi-Pr)3. Diastereoselectivity
was determined by NMR integration of the crude reaction
mixture (96:4 dr, undetectable amounts of other two diaster-
eomers). An authentic mixture of diastereomers was prepared
by the nonstereoselective addition of the corresponding lithium
enolate. Pure 4l was obtained in 85% yield after column
chromatography with 40% EtOAc/hexanes to 75% EtOAc/
hexanes as eluent: [R]23D -53.1 (c 1.0, CHCl3); IR 1049, 1715,
2980 cm-1; 1H NMR (400 MHz) δ 1.16 (d, 3H, J ) 7.2), 1.24 (s,
9H), 2.92 (m, 1H), 3.65 (s, 3H), 4.47 (d, 1H, J ) 3.5), 4.69 (m,
1H), 7.26-7.35 (m, 5H); 13C NMR (100 MHz) δ 12.3, 22.7, 46.1,
52.0, 55.8, 59.8, 127.9, 127.9, 128.3, 139.1, 174.9. Anal. Calcd
eluent: [R]23 -73.6 (c 1.0, CHCl3); IR 1037, 1513, 1615, 1732
D
cm-1; 1H NMR (400 MHz) δ 1.20 (s, 9H), 1.24 (d, 3H, J ) 6.7),
2.76 (m, 1H), 2.97-3.05 (m, 2H), 3.56-3.60 (m, 1H), 3.62 (s,
3H), 3.78 (s, 3H), 4.09 (d, 1H, J ) 5.9), 6.80-6.83 (m, 2H),
7.07-7.10 (m, 2H); 13C NMR (100 MHz) δ 17.8, 22.5, 33.4, 51.6,
51.7, 53.0, 55.1, 55.5, 113.9, 129.6, 130.4, 158.1, 173.8. Anal.
7828 J . Org. Chem., Vol. 67, No. 22, 2002