V. P. Krasno6 et al. / Tetrahedron: Asymmetry 14 (2003) 1985–1988
1987
1
102 elemental analyser and were in good agreement
1N HCl, water, 5% NaHCO , water and dried
3
with the calculated values.
(MgSO ). The solution was evaporated in vacuum to
4
dryness to give an yellow oily residue which was recrys-
tallized from hexane–ethyl acetate yielding amide 6a as
colourless crystals (0.48 g, 39%, de 99.2%). Mp: 158–
4
.2. N-[N%-Tosyl-(2S)-prolyl]-(3RS)-2,3-dihydro-3-
methyl-4H-1,4-benzoxazine 6a,b
20
6
0°C; [h]D −330 (c 1.1, CHCl ). Anal. calcd for
3
Solution of N-tosyl-(S)-prolyl chloride 5 (0.29 g, 1.0
mmol) in benzene (1.5 mL) was added dropwise to a
stirred solution of racemic 1 (0.15 g, 1.0 mmol) and
TEA (0.14 mL, 1.0 mmol) in benzene (1.5 mL). The
mixture was stirred at room temperature for 20 h, then
washed consequently with 1N HCl, water, 5%
NaHCO , water and dried (MgSO ). The solution was
C H N O S: C, 62.98; H, 6.04; N, 6.99; S, 8.01.
21 24 2 4
1
Found: C, 62.78; H, 6.08; N, 6.99; S, 7.96. H NMR
(DMSO-d ): 1.12 (d, J=6.8 Hz, 3H, CH -benzoxazine);
6
3
4
3
4
1.62 (m, 1H, C H-proline); 2.00 (m, 2H, C H-C H-pro-
line); 2.11 (m, 1H, C H-proline); 2.36 (s, 3H, CH -
C H ); 3.29 (ddd, J=9.8, 7.2, 5.9 Hz, 1H, C H-proline);
3.44 (ddd, J=9.8, 7.1, 6.0 Hz, 1H, C H-proline); 4.17
(dd, J=10.7, 1.9 Hz, 1H, C H-benzoxazine); 4.21 (dd,
J=10.7, 2.7 Hz, 1H, C H-benzoxazine); 4.61 (dd, J=
8.2, 4.5 Hz, 1H, C H-proline); 4.82 (qdd, J=6.8, 2.7,
1.9 Hz, 1H, C H-benzoxazine); 6.88 (ddd, J=8.1, 7.3,
1.5 Hz, 1H, C H-benzoxazine); 6.94 (dd, J=8.2, 1.5
Hz, 1H, C H-benzoxazine); 7.14 (ddd, J=8.2, 7.3, 1.6
Hz, 1H, C H-benzoxazine); 7.25 (d, J=8.1 Hz, 3H,
3
3
5
6
4
5
3
4
2
evaporated in vacuum to dryness to give a yellow oily
residue that was treated with hexane yielding amide
2
1
2
6
a,b as yellow crystals (0.28 g, 70%). H NMR (DMSO-
3
d ): 1.12 d and 1.14 d (J=6.8 Hz, 3H, CH -benzox-
6
3
3
4
6
azine); 1.6–2.1 (m, 4H, C H -C H -proline); 2.37 s and
2
2
5
8
2
4
.39 s (3H, CH -C H ); 3.3–3.5 (m, 2H, C H -proline);
3
6
4
2
7
.2 (m, 2H, O-CH ); 4.62 dd, J=8.2, 4.5 Hz, and 5.00
2
2
5
dd, J=8.4, 4.0 Hz (1H, C H-proline); 4.83 m and 4.81
m (1H, C H-benzoxazine); 7.7–6.9 (m, 8H, arom.).
C H-benzoxazine and 2H-tosyl); 7.33 (d, J=8.1 Hz,
3
2H, tosyl).
4
.3. N-[N%-Tosyl-(2S)-prolyl]-(2RS)-2-methyl-1,2,3,4-
4.6. N-[N%-Tosyl-(2S)-prolyl]-(2R)-2-methyl-1,2,3,4-tet-
rahydroquinoline 7a
tetrahydroquinoline 7a,b
Following the above procedure, and starting with
Following the above procedure, and starting with
racemic 2 (1.00 g, 6.8 mmol) and N-tosyl-(S)-prolyl
chloride 5 (0.98 g, 3.4 mmol) the title compound was
obtained as a yellowish residue (1.11 g, 82%) which was
recrystallized from hexane–ethyl acetate yielding amide
racemic amine 2 (0.15 g, 1.0 mmol) the title compound
1
was obtained as yellow crystals (0.27 g, 66%). H NMR
(
DMSO-d ): 1.03 d and 1.04 d (J=6.5 Hz, 3H, CH -
6 3
3
quinoline); 1.30 (m, 1H, C H-quinoline); 1.52 (m, 1H,
C H-quinoline); 1.98 (m, 3H, C H -C H-proline,); 2.33
s and 2.38 s (3H, CH -C H ); 2.38 (m, 1H, C H-quino-
line); 2.68 (m, 2H, C H -quinoline); 3.33 (m, 2H, C H -
4
3
4
7a as colourless crystals (0.65 g, 48%, de 99.0%). Mp:
2
3
20
147–149°C; [h]D −372 (c 2.0, CHCl ). Anal. calcd for
3
6
4
3
4
5
C H N O S: C, 66.30; H, 6.58; N, 7.03; S, 8.04.
Found: C, 66.13; H, 6.63; N, 7.09; S, 8.17. H NMR
2
2
22 26
2
3
1
proline); 4.28 dd, J=8.0, 4.7 Hz, and 4.89 dd, J=8.1,
2
4
(
.5 Hz (1H, C H-proline); 4.66 ddq and 4.73 ddq
(DMSO-d ): 1.04 (d, J=6.7 Hz, 3H, CH -quinoline);
6
3
2
3
J=7.4, 6.8, 6.6 Hz, 1H, C H-quinoline); 7.7–7.0 (m,
1.30 (dddd, J=13.2, 9.2, 7.1, 6.2 Hz, 1H, C H-quino-
line); 1.52 (m, 1H, C H-quinoline); 2.00 (m, 3H, C H -
C H-proline,); 2.33 (s, 3H, CH -C H ); 2.38 (m, 1H,
C H-quinoline); 2.63 (ddd, J=14.6, 5.8, 5.3 Hz, 1H,
C H-quinoline); 2.68 (ddd, J=14.6, 5.5, 4.8 Hz, 1H,
C H-quinoline); 3.23 (ddd, J=9.9, 7.1, 5.9 Hz, 1H,
C H-proline); 3.41 (ddd, J=9.9, 7.0, 6.2 Hz, 1H, C H-
proline); 4.28 (dd, J=7.9, 4.8 Hz, 1H, C H-proline);
4
3
8H, arom.).
2
4
3
6
4
3
4
8
.4. N-[N%-Tosyl-(2S)-prolyl]-(2RS)-2-methylindoline
a,b
4
4
5
5
Following the above procedure, and starting with
2
racemic amine 3 (0.13 g, 1.0 mmol) the title compound
1
2
was obtained as yellow crystals (0.26 g, 70%). H NMR
4.73 (ddq, J=7.5, 6.8, 6.7 Hz, 1H, C H-quinoline); 6.99
(dd, J=7.5, 1.3 Hz, 1H, C H-quinoline); 7.13 (d, J=
5
(
(
2
DMSO-d ): 1.24 d, J=6.5 Hz, and 1.31 d, J=6.5 Hz
6
4
3H, CH -indoline); 1.76 (m, 1H, C H-proline); 1.84–
8.2, Hz, 2H, tosyl); 7.19 (d, J=8.2, Hz, 2H, tosyl); 7.20
3
3
4
6
.24 (m, 3H, C H -C H-proline); 2.34 s and 2.40 s (3H,
(ddd, J=7.5, 7.3, 2.1 Hz, 1H, C H-quinoline); 7.25
2
7
CH -C H ); 2.66 d, J=16.0 Hz, and 2.70 d, J=16.4 Hz
(ddd, J=7.3, 7.3, 1.3 Hz, 1H, C H-quinoline); 7.31 (dd,
3
6
4
3
5
8
(
1H, C H-indoline); 3.40 (m, 3H, C H -proline and
C H-indoline); 4.61 dqd, J=8.7, 6.3, 1.3 Hz, and 4.86
dqd, J=8.5, 6.5, 2.1 Hz (1H, C H-indoline); 4.68 dd,
J=7.3, 2.1 Hz, 1H, C H-quinoline).
2
3
2
4.7. N-[N%-Tosyl-(2S)-prolyl]-(2R)-2-methylindoline 8a
J=8.6, 3.4 Hz, and 4.70 dd, J=7.8, 4.1 Hz (1H,
2
C H-proline); 7.00–7.90 (m, 8H, arom.).
Following the above procedure, and starting with
racemic 3 (1.00 g, 7.5 mmol) and N-tosyl-(S)-prolyl
chloride 5 (1.08 g, 3.8 mmol) the title compound was
obtained as a yellowish residue (1.00 g, 69%) which was
recrystallized twice from hexane–ethyl acetate yielding
amide 8a as colourless crystals (0.40 g, 28%, de 98.8%).
4
.5. N-[N%-Tosyl-(2S)-prolyl]-(3R)-2,3-dihydro-3-
methyl-4H-1,4-benzoxazine 6a
Solution of N-tosyl-(S)-prolyl chloride 5 (0.89 g, 3.1
mmol) in benzene (20 mL) was added dropwise to a
stirred solution of racemic 1 (0.93 g, 6.2 mmol) in
benzene (20 mL). The mixture was stirred at room
temperature for 20 h, then washed consequently with
2
0
Mp: 207–209°C; [h]D −78 (c 1.1, CHCl ). Anal. calcd
3
for C H N O S: C, 65.60; H, 6.29; N, 7.29; S, 8.34.
Found: C, 65.83; H, 6.27; N, 7.31; S, 8.34. H NMR
21
24
2
3
1
(DMSO-d ): 1.31 (d, J=6.3 Hz, 3H, CH -indoline);
6
3