Notes
J . Org. Chem., Vol. 66, No. 10, 2001 3651
Sch em e 1
with ether. The combined organic phases were washed with
brine, dried over anhydrous sodium sulfate, and concentrated.
The residue was purified with silica gel column chromatography
eluted with ethyl acetate-hexane (1:6; containing 0.5% triethy-
lamine) to give white crystals of 4a (2.34 g, 89%): mp 92.5-
2
3
9
1
1
3.5 °C (hexane); [R]
D
3
-2.2 (c 2.00, CHCl ); IR (KBr) 1741,
-
1
1
685, 1328 cm ; H NMR δ 6.70 (s, 1H), 6.68 (d, J ) 8.0 Hz,
H), 6.64 (d, J ) 8.0 Hz, 1H), 5.88 (s, 1H), 5.86 (s, 1H), 3.83 (dd,
J ) 9.6, 2.8 Hz, 1H), 3.81 (septet, J ) 6.8 Hz, 2H), 3.69 (d, J )
1
9
4.4 Hz, 1H), 3.07 (dd, J ) 13.2, 2.8 Hz, 1H), 2.87 (dd, J ) 13.2,
.6 Hz, 1H), 2.78 (d, J ) 14.4 Hz, 1H), 2.43 (td, J ) 13.2, 4.4
Hz, 1H), 2.15 (m, 1H), 1.83-1.70 (m, 2H), 1.45-1.40 (m, 1H),
1
1
(
.37 (s, 9H), 1.33 (d, J ) 6.8 Hz, 6H), 1.31 (d, J ) 6.8 Hz, 6H),
.06 (s, 3H), 1.03 (d, J ) 17.2 Hz, 1H), 0.84-0.76 (m, 1H), 0.74
s, 3H); 13C NMR δ 181.3, 170.9, 147.0, 145.9, 132.2, 122.8, 110.4,
1
07.8, 100.7, 80.6, 66.6, 55.0, 53.2, 48.1, 47.6, 43.4, 38.2, 34.8,
7.9, 27.1, 26.9, 22.5, 22.1, 19.8, 19.2; HRMS calcd for C30
S 562.3077, found 562.3094. Anal. Calcd for C30
C, 64.03; H, 8.24; N, 4.98; O, 17.06; S, 5.07. Found: C, 63.90; H,
2
46
H -
O
6
N
2
46 6 2
H O N S:
8
.32; N, 5.01; O, 16.71; S, 5.44.
2R,1′S)-1,1-Dim et h ylet h yl 2-(N,N-b is(1-m et h ylet h yl)-
,7-d im eth yl-1-m eth a n esu lfon a m id o-bicyclo[2.2.1]Hep t-2-
(
7
ylid en ea m in o)-3-(3,4-d im eth oxylp h en yl)p r op a n oa te (4b).
To a 50 mL flask containing tetrahydrofuran (10 mL) and
diisopropylamine (0.73 mL, 5.6 mmol) was added butyllithium
(2.2 M, 2.34 mL, 5.14 mmol) at -78 °C with stirring. The mixture
was warmed to 0 °C for 30 min and then was cooled to -78 °C.
Schiff base 2 (2.00 g, 4.67 mmol) in THF (5 mL) was dropwise
added to the mixture. The resulting mixture was stirred for 30
min, and then a THF solution (5 mL) containing 3,4-dimethoxy-
lbenzyl bromide (1.17 g, 5.06 mmol) and HMPA (1.65 mL, 9.35
mmol) was added. The mixture was stirred for 2 h, warmed to
room temperature, and quenched with the addition of water. The
resulting mixture was extracted with ether. The combined
organic phases were washed with brine, dried over anhydrous
sodium sulfate, and concentrated. The residue was purified with
silica gel column chromatography eluted with ethyl acetate-
with ethyl acetate-hexane (1:13) to afford thione 3 (25.9 g, 78.8
2
3
mmol, 74%) as orange crystals: mp 86.7-87.5 °C (hexane); [R]
D
-
1 1
1
(
1
)
81.5 (c 2.00, CHCl
d, J ) 14.8 Hz, 1H), 3.79 (septet, J ) 6.4 Hz, 2H), 2.89 (d, J )
4.8 Hz, 1H), 2.82-2.72 (m, 1H), 2.72-2.65 (m, 1H), 2.46 (d, J
20.8 Hz, 1H), 2.20-1.95 (m, 2H), 1.50-1.30 (m, 2H), 1.33 (d,
J ) 6.4 Hz, 6H), 1.32 (d, J ) 6.4 Hz, 6H), 1.23 (s, 3H), 0.83 (s,
3
); IR (KBr) 1328, 1133 cm ; H NMR δ 3.89
hexane (1:4; containing 0.5% triethylamine) to give white
1
3
23
3
2
3
5
8
H); C NMR: δ 265.5, 69.5, 54.6, 53.6, 49.4, 48.0, 44.7, 29.4,
crystals 4b (2.25 g, 83.3%): mp 115.0-116.0 °C (hexane); [R]
D
-
1 1
6.7, 22.3, 21.8, 20.2, 19.5; HRMS calcd for
31.1640, found 331.1640. Anal. Calcd for C16
C
29
16
H
29
O
2
2
NS
C,
2
3
92.5 (c 1.00, CHCl ); IR (KBr) 1728, 1690, 1326 cm ; H NMR
H
O
2
NS
:
δ 6.74 (s, 2H), 6.72 (s, 1H), 3.87 (dd, J ) 10.0, 3.6 Hz, 1H), 3.86
(s, 3H), 3.84 (septet, J ) 7.2 Hz, 2H), 3.82 (s, 3H), 3.73 (d, J )
14.0 Hz, 1H), 3.11 (dd, J ) 13.2, 3.6 Hz, 1H), 2.89 (dd, J ) 13.2,
10.0 Hz, 1H), 2.74 (d, J ) 14.0 Hz, 1H), 2.38 (td, J ) 12.4, 3.6
Hz, 1H), 2.13 (dt, J ) 16.8, 4.0 Hz, 1H), 1.80-1.60 (m, 2H), 1.40-
1.30 (m, 2H), 1.38 (s, 9H), 1.34 (d, J ) 7.2 Hz, 6H), 1.31 (d, J )
7.2 Hz, 6H), 1.02 (s, 3H), 0.93 (d, J ) 16.8 Hz, 1H), 0.71 (s, 3H);
7.96; H, 8.82; N, 4.22; O, 9.65; S, 19.34. Found: C, 57.91; H,
.81; N, 4.27; O, 9.55; S, 19.45.
(
1S)-1,1-Dim et h ylet h yl 2-(N,N-Bis(1-m et h ylet h yl)-7,7-
dim eth yl-1-m eth an esu lfon am idobicyclo[2.2.1]h ept-2-ylide-
4
a,8
n ea m in o)eth a n oa te (2).
A mixture of tert-butyl glycinate
(157 mg, 1.20 mmol) and thione 3 (331 mg, 1.00 mmol) in toluene
1
3
(7 mL) was heated under reflux for 24 h. After cooling, the
C NMR δ 180.7, 170.8, 148.3, 147.3, 131.1, 121.7, 113.1, 110.9,
80.3, 66.6, 55.8, 55.7, 54.7, 52.7, 47.9, 47.5, 43.1, 38.0, 34.5, 27.8,
mixture was filtered. The filtrate was concentrated and purified
by silica gel column chromatography eluted with ethyl acetate-
hexane (1:5) to give Schiff base 2 (417 mg, 98%): mp 68.0-69.5
26.9, 26.6, 22.4, 21.9, 19.5, 19.0; HRMS calcd for C31
578.3390, found 578.3342.
50 6 2
H O N S
2
3
°
C (hexane); [R]
D
23.5 (c 2.00, CHCl
3
); IR (KBr) 1735, 1684
(R)-1,1-Dim eth yleth yl 2-a m in o-3-(3,4-m eth ylen ed ioxyl-
-
1
1
8
cm ; H NMR δ 3.94, 3.92 (ABq, J ) 16.0 Hz, 2H), 3.77 (septet,
J ) 6.8 Hz, 2H), 3.70 (d, J ) 14.4 Hz, 1H), 2.86 (d, J ) 14.4 Hz,
p h en yl)p r op a n oa te (5a ). A 25 mL flask was charged with 4a
(1.00 g, 1.79 mmol), sodium hydroxide (86 mg, 2.1 mmol), acetic
acid (0.123 mL, 2.14 mmol), NH OH‚HCl (149 mg, 2.14 mmol),
2
1
3
1
H), 2.61 (ddd, J ) 12.2, 12.0, 4.4 Hz, 1H), 2.27 (ddd, J ) 16.8,
.6, 3.6 Hz, 1H), 1.97-1.87 (m, 2H), 1.79 (d, J ) 16.8 Hz, 1H),
.56-1.54 (m, 1H), 1.43 (s, 9H), 1.31 (d, J ) 6.8 Hz, 6H), 1.30
methanol (10 mL), and chloroform (6 mL). The mixture was
stirred at room temperature for 24 h and then was concentrated,
neutralized with 2 N HCl (5 mL), and extracted with ether three
times. The organic layer was washed with water, dried over
anhydrous sodium sulfate, filtered, and concentrated to recover
chiral auxiliary (510 mg, 91%). Combined aqueous layers were
neutralized with NaOH to pH 10-11 and then extracted with
ether. Combined organic layers were washed with brine, dried
over anhydrous sodium sulfate, filtered, and concentrated to give
(d, J ) 6.8 Hz, 6H), 1.30-1.20 (m, 1H), 1.16 (s, 3H), 0.83 (s,
1
3
3
4
H); C NMR δ 183.3, 169.2, 80.7, 55.1, 54.7, 52.8, 48.0, 47.7,
3.8, 34.9, 27.9, 27.2, 27.0, 22.5, 21.9, 20.0, 19.4; HRMS calcd
for C22
for C22
Found: C, 61.60; H, 9.45; N, 6.50; O, 13.62; S, 8.84.
2R,1′S)-1,1-Dim et h ylet h yl 2-(N,N-Bis(1-m et h ylet h yl)-
,7-d im et h yl-1-m et h a n esu lfon a m id obicyclo[2.2.1]h ep t -2-
y lid e n e a m in o )-3-(3,4-m e t h y le n e d io x y lp h e n y l)p r o p a -
H
H
41
O
4
N
4 2
2
S (M + 1), 429.2788, found 429.2796. Anal. Calcd
40
O N S: C, 61.65; H, 9.41; N, 6.54; O, 14.93; S, 7.48.
(
2
3
7
aminoester 5a (420 mg, 89%) as a pale yellow liquid: [R]
D
-8.2
-
1 1
(c 2.00, CHCl
3
); IR (neat) 3384, 3314, 1729, 1611 cm ; H NMR
4
a
n oa te (4a ). To a 50 mL flask containing tetrahydrofuran (5
mL) and diisopropylamine (0.73 mL, 5.6 mmol) was added
butyllithium (2.2 M, 2.34 mL, 5.14 mmol) at -78 °C with
stirring. The mixture was warmed to 0 °C for 30 min and then
was cooled to -78 °C. Schiff base 2 (2.00 g, 4.67 mmol) in THF
δ 6.72 (d, J ) 8.0 Hz, 1H), 6.69 (d, J ) 1.6 Hz, 1H), 6.63 (dd, J
) 8.0, 1.6 Hz, 1H), 5.91 (s, 2H), 3.52 (dd, J ) 5.2, 8.0 Hz, 1H),
2.94 (dd, J ) 13.6, 5.2 Hz, 1H), 2.73 (dd, J ) 13.6, 8.0 Hz, 1H),
1.44 (s, 9H); 13C NMR δ 174.2, 147.6, 146.3, 131.1, 122.3, 109.6,
108.1, 100.8, 81.1, 56.3, 40.7, 28.0; HRMS calcd for C14
265.1314, found 265.1324.
19 4
H O N
(5 mL) was dropwise added to the mixture. The resulting
mixture was stiired for 30 min, and then a THF solution (5 mL)
containing 3,4-methylenedioxylbenzyl bromide (1.14 g, 5.30
mmol) and HMPA (1.65 mL, 9.35 mmol) was added. The mixture
was stirred for 1 h, warmed to room temperature, and quenched
with the addition of water. The resulting mixture was extracted
(R)-1,1-Dim eth yleth yl 2-a m in o-3-(3,4-d im eth oxylp h en -
yl)p r op a n oa te (5b). A 25 mL flask was charged with 4b (130
mg, 0.225 mmol), sodium hydroxide (10.8 mg, 0.270 mmol), acetic
acid (0.015 mL, 0.27 mmol), NH
2
OH‚HCl (18.8 mg, 0.270 mmol),
methanol (3 mL), and chloroform (2 mL). The mixture was