2
224 J . Org. Chem., Vol. 61, No. 6, 1996
Notes
Typ ica l P r oced u r e for th e Ad d ition of Ester En ola tes
246, 221, 155, 139, 107, 91, 57; HRMS calcd for C19
360.1507, found 360.1517. Anal. Calcd for C19
63.31; H, 6.71; N, 7.77. Found: C, 63.02; H, 6.99; N, 7.42.
(R ,S)-Ben zyl â-[N-(p-Tolylsu lfin yl)am in o]-3-pyr idin epr o-
H
24
N
2
SO
3
,
to Su lfin im in es: (R
th a len esu lfin yl)a m in o]-3-p yr id in ep r op a n oa te (7f). In a
00 mL dry single-necked round bottom flask equipped with a
s
,S)-(-)-Eth yl â-[N-(2-Meth oxyn a p h -
24 2 3
H N O S: C,
1
s
magnetic stir bar, argon inlet, and rubber septum was placed
freshly distilled THF (27.0 mL). The solution was cooled to -78
C, 7.50 mL of LiHMDS (1.0 M solution in THF, 7.5 mmol, 1.6
equiv) was added followed by 0.69 mL of anhydrous ethyl acetate
7.03 mmol, 1.5 equiv). The reaction mixture was stirred for 50
p a n oa te (7d ). The crude compound was purified by preparative
thin layer chromatography (10% ethanol/ethyl acetate): thick
gum; yield 65%; 72% de; IR (neat) 1734, 1577, 1491, 1427, 1277,
°
-
1 1
3
1159, 1089, 1062, 811, 698 cm ; H NMR (CDCl ) δ 2.34 (s, 14/
(
100 3H), 2.43 (s, 86/100 3H), 2.93 (d, 86/100 2H, J ) 6.3 Hz),
3.04-3.06 (m, 14/100 2H), 4.75 (q, 14/100 1H, J ) 6.5 Hz), 4.91
(q, 86/100 1H, J ) 6.1 Hz), 5.03 (s, 86/100 2H), 5.06 (s, 14/100
2H), 5.15 (d, 86/100 1H, J ) 6.0 Hz), 5.45 (d, 14/100 1H, J )
7Hz), 7.18-7.76 (m, 11H), 8.47 (d, 14/100 1H, J ) 2.0 Hz), 8.43-
8.45 (m, 14/100 1H), 8.54-8.57 (m, 86/100 1H) 8.65 (d, 86/100
min at which time a solution of 1.45 g (4.69 mmol) of (R)-(-)-6
in THF (12.0 mL) was added dropwise via syringe at -78 °C.
After stirring for 5.5 h the reaction was quenched at -78 °C by
4
addition of saturated NH Cl solution (3 mL), warm to room
temperature, and diluted with ethyl acetate (75 mL). The
organic layer was washed with water (20 mL), the aqueous
portion was extracted with ethyl acetate (50 mL), and the
combined organic extracts were washed with water (25 mL) and
+
1H, J ) 2.0 Hz); MS m/ z 394 (M ), 377, 346, 238, 180, 165,
139, 105, 91, 77; HRMS calcd for C22
H
22
N
2
SO
3
, 395.1429, found
395.1428. Anal. Calcd for C22
22 2 3
H N O S: C, 66.98; H, 5.62; N,
brine (20 mL) and dried (MgSO
gave an oil [78% de by H NMR] which was purified by silica
gel column chromatography (90% EtOAc/petroleum ether to 5%
4
). Concentration of the solvent
7.10. Found: C, 67.19; H, 5.88; N, 6.77.
1
(()-Meth yl â-[N-(2-Meth oxyn aph th alen esu lfin yl)am in o]-
3-p yr id in ep r op a n oa te (7e). The crude compound was purified
by preparative thin layer chromatography (10% ethanol/ethyl
acetate): yield 86%; 72% de. Major isomer: yield 74%; IR (neat)
methanol/ethyl acetate) to afford 1.39 g (76%) of (R
S
,S)-(-)-7f
(
>99% de) and of 0.16 g (9%) of (R ,R)-7f (minor diastereomer).
S
2
0
-1 1
Major diastereomer: thick oil; [R]
D
-80.0° (c 1.25, CHCl
3
); IR
1732, 1592, 1506, 1431, 1272, 1250, 1064, 1024 cm ; H NMR
-
1
(
KBr) 3248, 2974, 1716, 1591, 1506, 1271, 1192, 1080, 1023 cm
;
(CDCl ) δ 2.85-3.05 (m, 2H), 3.69 (s, 3H), 4.12 (s, 3H), 5.02 (q,
3
1
H NMR (CDCl
3
) δ 1.23 (t, 3H, J ) 7.2 Hz), 2.90-3.05 (m, 3H),
1H, J ) 5.5 Hz), 7.13 (d, 1H, J ) 4.1 Hz), 7.23-7.54 (m, 4H),
7.71 (d, 1H, J ) 6.9 Hz), 7.80 (d, 1H, J ) 8.1 Hz), 7.95 (d, 1H,
J ) 9.1 Hz), 8.39 (d, 1H, J ) 8.5 Hz), 8.55 (d, 1H, J ) 4.7 Hz),
4
1
7
.13 (s, 3H), 4.15 (q, 2H, J ) 6.4), 5.02 (q, 1H, J ) 6.3), 7.13 (d,
H, J ) 4.3), 7.20-7.55 (m, 4H), 7.71 (dd, 1H, J ) 7.8, 1.5 Hz),
.78 (d, 1H, J ) 8.1), 7.94 (d, 1H, J ) 9.0), 8.40 (d, 1H, J ) 8.5
8.65 (bs, 1H); HRMS calcd for C20
found 385.1224.
20
H N SO , 385.1222 (M + 1),
2
4
1
3
Hz), 8.55 (d, 1H, J ) 4.7), 8.66 (s, 1H); C NMR δ 170.6, 155.5,
1
1
49.3, 149.0, 135.7, 135.0, 133.5, 130.6, 128.8, 128.5, 128.1, 125.4,
24.4, 123.3, 121.9, 113.4, 60.9, 56.8, 53.7, 42.0, 14.0; HRMS
Minor diastereomer: yield 12%; IR (neat) 1734, 1619, 1592,
-
1
1
1507, 1431 1272, 1251, 1063, 1024, 813, 712 cm ; H NMR δ
3.00 (ddd, 2H, J ) 61.2, 16.1, 6.0 Hz), 3.58 (s, 3H), 4.07 (s, 3H),
4.98 (q, 1H, J ) 7.0 Hz), 6.48 (d, 1H, J ) 5.5 Hz), 7.25-7.55 (m,
4H), 7.80 (d, 2H, J ) 8.0 Hz), 7.94 (d, 1H, J ) 9.1 Hz), 8.52-
8.59 (m, 3H); MS m/ z 385 (M + 1), 336, 205, 179.
calcd for C21
Minor isomer (R
22 2 4
H N O S 399.1379 (M + 1), found 399.1386.
1
s
3
,R)-7f, H NMR (CDCl ) δ 1.12 (t, 3H, J )
7
4
.1 Hz), 2.98 (ddd, 2H, J ) 63.0, 16.0, 7.5 Hz), 4.02 (q, 2H, J )
Hz), 4.05 (s, 3H), 4.98 (q, 1H, J ) 6.5 Hz), 6.49 (d, 1H, J ) 5.6
Hz), 7.23-7.57 (m, 4H), 7.77-7.81 (m, 2H), 7.91 (d, 1H, J ) 9.0
Hz), 8.51-8.59 (m, 3H); MS m/ z 399 (M + 1), 378, 346, 205,
1
(()-Ben zyl â-[N-(2-Meth oxyn a p h th a len esu lfin yl)a m in o]-
3-p yr id in ep r op a n oa te (7g). The crude compound was purified
by preparative thin layer chromatography (10% ethanol/ethyl
acetate): oil; yield 87%; 72% de. Major diastereomer yield 75%;
IR (neat) 1727, 1592, 1508, 1272, 1251, 1152, 1064, 1024, 812,
95, 189, 115, 107, 80.
(
R,3S)-Meth yl â-[N-(p-Tolylsu lfin yl)am in o]-3-pyr idin epr o-
p a n oa te (7a ). yield 80% (thick gum); 74% de; IR (neat) 3176,
-
1
1
-1
1
2
950, 1735, 1593, 1435, 1089, 1055, 812, 713 cm
;
H NMR
3
750 cm ; H NMR (CDCl ) δ 2.92-3.10 (m, 2H), 4.08 (s, 3H),
(
CDCl ) δ 2.34 (s, 13/100 3H), 2.42 (s, 87/100 3H), 2.89 (d, 87/
3
5.05 (q, 1H, J ) 5.2 Hz), 5.11 (s, 2H), 7.12 (d, 1H, J ) 4.7 Hz),
7.24-7.53 (m, 9H), 7.65-7.71 (m, 1H), 7.80 (d, 1H, J ) 7.9 Hz),
7.95 (d, 1H, J ) 9.1 Hz), 8.38 (d, 1H, J ) 8.6 Hz), 8.55 (d, 1H,
1
8
4
5
1
00 2H, J ) 6.3 Hz), 3.03 (d, 13/100 2H, J ) 6.0 Hz), 3.62 (s,
7/100 3H), 3.64 (s, 13/100 3H), 4.77 (q, 13/100 1H, J ) 7.4 Hz),
.89 (q, 87/100 1H, J ) 6.2 Hz), 5.33 (d, 87/100 1H J ) 6.2 Hz),
.63 (d, 13/100 1H, J ) 7.8 Hz), 7.16-7.82 (m, 6H), 8.38 (br s,
J ) 3.7 Hz), 8.65 (bs, 1H); HRMS calcd for C26
461.1535 (M + 1), found: 461.1528.
24 2 4
H N SO ,
3/100 1H), 8.44 (d, 13/100 1H, J ) 4.1 Hz), 8.56 (d, 87/100 1H,
Minor diastereomer: yield 12%; IR (neat) 1734, 1654, 1636,
+
1 1
J ) 4.0 Hz), 8.67 (br s, 87/100 1H); MS m/ z 318 (M ), 301, 270,
2
3
C H N O
16 18 2 3
5
3
1618, 1271, 1250, 1063, 1024 cm ; H NMR (CDCl ) δ 3.05 (ddd,
38, 180, 165, 139, 105, 91, 77; HRMS calcd for C16
19.1116 (M 1), found 319.1118. Anal. Calcd for
S: C, 60.36; H, 5.69; N, 8.79. Found: C, 60.11; H,
.82; N, 8.44.
R,3S)-Eth yl â-[N-(p-Tolylsu lfin yl)a m in o]-3-p yr id in ep r o-
H
18
N
2
SO
3
,
2H, J ) 64.7, 16.0, 7.5 Hz), 4.04 (s, 3H), 4.89-5.15 (m, 2H), 6.46
(d, 1H, J ) 5.6Hz), 7.17-7.54 (m, 9H), 7.79 (t, 2H, J ) 8.1 Hz),
7.93 (d, 1H, J ) 9.1 Hz), 8.52-8.58 (m, 3H); MS m/ z 461 (M +
1), 412, 255, 205, 107.
+
(
(S)-(+)-Eth yl 3-Am in o-3-p yr id in ep r op a n oa te (3). In a 50
mL dry single-necked round bottom flask fitted with magnetic
stir bar, argon inlet and rubber septum was placed 1.08 g (2.71
p a n oa te (u sin g LiHMDS) (7b). The crude compound was
purified by silica gel chromatography (10% ethanol/ethyl ace-
tate): yield 59%; 52% de; IR (neat) 3021, 2924, 1731, 1619, 1592,
mmol) of (R ,S)-(-)-ethyl â-[N-(2-methoxynaphthalenesulfinyl)-
s
1
3
3
429, 1271, 1250, 1063 cm-1; 1H NMR (CDCl
H, J ) 7.1 Hz), 1.17 (t, 24/100 3H, J ) 7.1 Hz), 2.35 (s, 24/100
H), 2.42 (s, 76/100 3H), 2.87 (d, 76/100 2H, J ) 6.2 Hz), 3.01
3
) δ 1.16 (t, 76/100
amino]-3-pyridinepropanoate (7f) in 20 mL of dry ethanol and
cooled to 0 °C. Trifluoroacetic acid (1.04 mL, 5.0 equiv) was
added, and the reaction mixture was stirred at rt for 2 h at which
time the solvent was removed to dryness below 40 °C on the
rotary evaporator. To remove traces of TFA, 5 mL of toluene
was added and the solvent removed. The residue was purified
(
m, 24/100 2H), 4.06 (q, 2H, J ) 7.2 Hz), 4.77 (q, 24/100 1H, J
)
7.0 Hz), 4.88 (q, 76/100 1H, J ) 6.2 Hz), 5.41 (d, 76/100 1H,
J ) 6.0 Hz), 5.74 (d, 24/100 1H, J ) 6.2 Hz), 7.16-7.80 (m, 6H),
8
7
.35 (br s, 24/100 1H), 8.44 (d, 24/100 1H, J ) 3.9 Hz), 8.57 (d+,
2 2
by silica gel chromatography (20% ethanol in CH Cl ), and the
resulting oil was dried under vacuum for 48 h to give 1.03 g
(90%) of (+)-(S)-3 as its bis-ditrifluoroacetic acid salt as thick
6/100 1H, J ) 4.0 Hz), 8.67 (br s, 76/100 1H); MS m/ z 333 (M
+
C
1), 315, 284, 193, 178, 147, 139, 107, 91, 78; HRMS calcd for
SO , 333.1273 (M + 1), found 333.1281.
,S)-ter t-Bu t yl â-[N-(p -Tolylsu lfin yl)a m in o]-3-p yr i-
2
0
15
20
17
H
21
N
2
3
pale yellow gum; [R]
D
+3.67° (c 7.1, DMF) [lit. [R]
D
+3.3°
1
(
R
s
(c, 10 DMF)]; H NMR (DMSO) δ 1.08 (t, 3H, J ) 7.1 Hz), 3.06
(m, 2H), 4.01 (qd, 2H, J ) 7.1, J ) 1 Hz), 4.70 (t, 1H, J ) 7.2
Hz), 7.49 (m, 1H), 7.91 (dt, 1H, J ) 7.9 Hz, J ) 1.9 Hz), 8.48
(bs, 1H), 8.58 (m, 1H), 8.67 (d, 1H, J ) 2.3 Hz).
d in ep r op a n oa te (7c). The crude compound was purified by
preparative thin layer chromatography (10% ethanol/ethyl
acetate): thick gum, yield 76%; 10% de; IR (neat) 1725, 1367,
1
286, 1152, 1089, 1054, 812, 713 cm-1; 1H NMR (CDCl
3
) δ 1.32
The enantiomeric purity of the (S)-(+)-3 was determined to
(s, 55/100 9H), 1.34 (s, 45/100 9H), 2.34 (s, 45/100 3H), 2.42 (s,
be >97% ee [1.4/98.6 R/S] using a Daicel CrownPak CR (+)
5
1
5
4
1
5/100 3H), 2.79 (dd, 55/100 2H, J ) 7.2, 1.2 Hz), 2.92 (d, 45/
00 2H, J ) 6.0 Hz), 4.74 (q, 45/100 1H, J ) 6.9 Hz), 4.86 (q,
5/100 1H, J ) 6.0 Hz), 5.29 (d, 55/100 1H, J ) 4.0 Hz), 5.63 (d,
5/100 1H, J ) 7.3 Hz), 7.14-7.81 (m, 6H), 8.37 (br s, 45/100
column under the following conditions: HClO
4
at pH ) 1, rt,
flow rate: 0.45 mL/min, UV detector at 200 nm.
(S)-(+)-Eth yl 3-Am in o-3-p yr id in ep r op a n oa te (3). Re-
cover y of (1S,2R,5S)-(()-Men t h yl 2-Met h oxy-1-n a p h t h a -
len esu lfin a te. In a 25 mL dry single-necked round bottom flask
equipped with magnetic stir bar, argon inlet and rubber septum
H), 8.42 (d, 45/100 1H, J ) 4.2 Hz), 8.55 (d, 55/100 1H, J ) 4.0
+
Hz), 8.66 (br s, 55/100 1H); MS m/ z 360 (M ), 343, 287, 278,