R. Grandel, U. Kazmaier
FULL PAPER
117Ϫ118°C. Ϫ HPLC (hexanes/ethyl acetate, 85:15): retention
anes, m.p. 53Ϫ54°C. Ϫ HPLC (hexanes/ethyl acetate, 85:15): reten-
time: 11.05 min (major diastereomer), 13.60 min (minor dia-
tion time: 12.21 min (major diastereomer), 15.01 min (minor dia-
stereomer). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 1.40 (s, 3 H), 2.39 stereomer). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 1.42 (s, 3 H), 2.41
(s, 3 H), 3.88 (d, J ϭ 6.6 Hz, 1 H), 4.80 (d, J ϭ 5.3 Hz, 1 H), 4.94 (s, 3 H), 3.83 (d, J ϭ 7.8 Hz, 1 H), 4.86 (d, J ϭ 7.7 Hz, 1 H), 4.99
(d, JAB ϭ 12.2 Hz, 1 H), 5.00 (d, JAB ϭ 12.2 Hz, 1 H), 5.92 (s, 1 (d, JAB ϭ 12.1 Hz, 1 H), 5.05 (d, JAB ϭ 12.1 Hz, 1 H), 5.77 (s, 1
H), 7.01 (d, J ϭ 8.5 Hz, 2 H), 7.17Ϫ7.36 (m, 9 H), 7.69 (d, J ϭ H), 6.99 (dd, J ϭ 8.3, 2.0 Hz, 1 H), 7.20Ϫ7.36 (m, 9 H), 7.71 (d,
8.3 Hz, 2 H). Ϫ 13C NMR (75 M Hz, CDCl3): δ ϭ 18.4, 21.5, 66.0,
J ϭ 8.3 Hz, 2 H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.6, 21.5,
68.0, 78.1, 122.4, 127.1, 128.3, 128.5, 128.7, 129.0, 129.6, 131.2, 66.3, 68.3, 77.5, 126.7, 127.0, 127.2, 128.5, 128.8, 129.3, 129.7,
134.6, 137.2, 139.0, 143.6, 171.5. Ϫ C24 H24BrNO5S (518.4): calcd.
130.1, 132.3, 132.4, 134.3, 138.6, 138.9, 143.8, 171.3. Ϫ
C 55.60, H 4.67, N 2.70; found C 55.64, H 4.68, N 2.66.
C24H23Cl2NO5S (508.4): calcd. C 56.70, H 4.56, N 2.76; found C
56.57, H 4.59, N 2.74.
1
syn-rac-12 (selected signals): H NMR (300 MHz, CDCl3): δ ϭ
1
syn-rac-15 (selected signals): H NMR (300 MHz, CDCl3): δ ϭ
2.36 (s, 3 H), 3.42 (bs, 1 H), 4.83 (s, 1 H), 5.95 (s, 1 H), 7.59 (d, J ϭ
8.3 Hz, 2 H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 17.0, 21.0, 172.4.
3.23 (bs, 1 H), 4.86 (bs, 1 H), 5.81 (s, 1 H), 7.58 (d, J ϭ 8.3 Hz, 2
H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 16.9, 19.8, 65.5, 68.0,
77.5, 172.3.
Benzyl (±)-anti-3-(4-Chlorophenyl)-3-hydroxy-2-methyl-2-[(4-
toluenesulfonyl)amino]propanoate (anti-rac-13): According to the
general procedure, the aldol reaction of N-(4-toluenesulfonyl)alan-
ine benzyl ester (rac-2) (134 mg, 0.4 mmol) with 4-chlorobenzal-
dehyde (68 mg, 0.48 mmol) yielded anti-rac-13 (164 mg, 87%) after
flash chromatography (hexanes/ethyl acetate, 75:25) as a colorless
solid, which was crystallized from dichloromethane/hexanes, m.p.
123Ϫ124°C. Ϫ HPLC (hexanes/ethyl acetate, 85:15): retention
time: 11.52 min (major diastereomer), 13.65 min (minor dia-
stereomer). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 1.43 (s, 3 H), 2.41
(s, 3 H), 3.71 (d, J ϭ 8.0 Hz, 1 H), 4.82 (d, J ϭ 7.2 Hz, 1 H), 4.98
(d, JAB ϭ 12.0 Hz, 1 H), 5.04 (d, JAB ϭ 12.0 Hz, 1 H), 5.73 (s, 1
H), 7.04 (d, J ϭ 8.5 Hz, 2 H), 7.17 (d, J ϭ 8.5 Hz, 2 H), 7.18Ϫ7.37
(m, 7 H), 7.72 (d, J ϭ 8.4 Hz, 2 H). Ϫ 13C NMR (75 MHz, CDCl3):
δ ϭ 18.7, 21.5, 66.2, 68.1, 78.2, 127.1, 128.3, 128.56, 128.62, 128.7,
Benzyl (±)-anti-3-(2,6-Dichlorophenyl)-3-hydroxy-2-methyl-2-
[(4-toluenesulfonyl)amino]propanoate (anti-rac-16): According to
the general procedure, the aldol reaction of N-(4-toluenesulfonyl)-
alanine benzyl ester (rac-2) (134 mg, 0.4 mmol) with 2,6-dichloro-
benzaldehyde (84 mg, 0.48 mmol) yielded anti-rac-16 (142 mg,
70%) after flash chromatography (hexanes/ethyl acetate, 8:2) as a
colorless oil. Ϫ HPLC (hexanes/ethyl acetate, 85:15): retention
time: 8.76 min (major diastereomer), 10.22 min (minor dia-
stereomer). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 1.49 (s, 3 H), 2.40
(s, 3 H), 3.92 (d, J ϭ 11.5 Hz, 1 H), 5.00 (d, JAB ϭ 12.5 Hz, 1 H),
5.10 (d, JAB ϭ 12. 5 Hz, 1 H), 5.61 (d, J ϭ 11.4 Hz, 1 H), 6.09 (s,
1 H), 7.15 (t, J ϭ 7.9 Hz, 1 H), 7.22Ϫ7.35 (m, 9 H), 7.75 (d, J ϭ
8.3 Hz, 2 H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.2, 21.5, 66.0,
68.3, 77.3, 127.0, 127.2, 128.1, 128.4, 128.6, 129.6, 129.7, 130.0,
131.8, 134.7, 139.2, 143.5, 171.2. Ϫ C24H23Cl2NO5S (508.4): calcd.
C 56.70, H 4.56, N 2.76; found C 56.96, H 4.75, N 2.53.
128.8, 129.7, 134.3, 134.4, 136.6, 139.0, 143.7, 171.4.
C24H24ClNO5S (474.0): calcd. C 60.82, H 5.10, N 2.96; found C
60.55, H 5.15, N 2.84.
Ϫ
1
syn-rac-16 (selected signals): H NMR (300 MHz, CDCl3): δ ϭ
1
syn-rac-13 (selected signals): H NMR (300 MHz, CDCl3): δ ϭ
3.72 (d, J ϭ 8.3 Hz, 1 H), 5.75 (d, J ϭ 8.0 Hz, 1 H), 6.03 (s, 1 H),
7.65 (d, J ϭ 8.4 Hz, 2 H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ
17.4, 19.9, 67.0, 68.2, 76.8, 139.5, 143.0, 172.5.
2.37 (s, 3 H), 2.80 (bs, 1 H), 4.83 (bs, 1 H), 5.07 (s, 2 H), 5.73 (s, 1
H), 7.61 (d, J ϭ 8.3 Hz, 2 H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ
17.0, 65.8, 67.9, 78.3, 135.9, 143.4, 172.8.
Benzyl (±)-3-Hydroxy-2-methyl-2-[(4-toluenesulfonyl)amino]-3-
(3,4,5-trimethoxyphenyl)propanoate (rac-17): According to the gen-
eral procedure, the aldol reaction of N-(4-toluenesulfonyl)alanine
benzyl ester (rac-2) (134 mg, 0.4 mmol) with 3,4,5 trimethoxybenz-
aldehyde (94 mg, 0.48 mmol) yielded rac-17 (159 mg, 75%) after
flash chromatography (hexanes/ethyl acetate, 65:35) as a colorless
solid, which was crystallized from dichloromethane/hexanes, m.p.
124Ϫ125°C. Diastereomeric ratio anti/syn 9:1. Major diastereomer:
Benzyl
(±)-anti-3-Hydroxy-2-methyl-3-(4-nitrophenyl)-2-[(4-
toluenesulfonyl)amino]propanoate (anti-rac-14): According to the
general procedure, the aldol reaction of N-(4-toluenesulfonyl)alan-
ine benzyl ester (rac-2) (134 mg, 0.4 mmol) with 4-nitrobenzal-
dehyde (73 mg, 0.48 mmol) yielded anti-rac-14 (116 mg, 60%) after
flash chromatography (hexanes/ethyl acetate, 8:2) as a colorless
solid, which was crystallized from dichloromethane/hexanes, m.p.
144Ϫ145°C. HPLC (hexanes/ethyl acetate, 85:15): retention time:
18.64 min (major diastereomer), 21.64 min (minor diastereomer).
1
HPLC (hexanes/ethyl acetate, 7:3): retention time: 8.85 min. Ϫ H
NMR (300 MHz, CDCl3): δ ϭ 1.47 (s, 3 H), 2.39 (s, 3 H), 3.76 (d,
J ϭ 7.6 Hz, 1 H), 3.76 (s, 6 H), 3.82 (s, 3 H), 4.85 (d, J ϭ 7.8 Hz,
1 H), 5.00 (s, 2 H), 5.68 (s, 1 H), 6.49 (s, 2 H), 7.16Ϫ7.34 (m, 7 H),
7.72 (d, J ϭ 8.30, 2 H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ 18.8,
21.5, 56.2, 60.8, 66.4, 67.8, 78.7, 104.7, 127.0, 127.8, 127.9, 128.58,
128.62, 128.7, 129.4, 129.6, 133.7, 134.6, 138.2, 139.1, 143.5, 153.0,
171.6. Minor diastereomer: HPLC (hexanes/ethyl acetate, 7:3): re-
1
Ϫ H NMR (300 MHz, CDCl3): δ ϭ 1.45 (s, 3 H), 2.41 (s, 3 H),
4.05 (bs, 1 H), 4.97 (d, JAB ϭ 12.0 Hz, 1 H), 5.02 (s, 1 H), 5.12 (d,
JAB ϭ 12.0 Hz, 1 H), 5.77 (s, 1 H), 7.21Ϫ7.42 (m, 9 H), 7.72 (d,
J ϭ 8.3 Hz, 2 H), 7.99 (d, J ϭ 8.7 Hz, 2 H). Ϫ 13C NMR (75
MHz, CDCl3): δ ϭ 18.8, 21.5, 66.4, 68.4, 77.8, 123.1, 127.0, 128.3,
128.8, 129.1, 129.5, 129.8, 134.2, 138.8, 143.9, 145.5, 147.7, 171.1.
Ϫ C24H24N2O7S (484.5): calcd. C 59.49, H 4.99, N 5.78; found C
59.40, H 5.01, N 5.74.
1
tention time: 10.24 min. Ϫ Selected signals: H NMR (300 MHz,
CDCl3): δ ϭ 2.36 (s, 3 H), 3.00 (bs, 1 H), 4.85 (bs, 1 H), 5.03 (d,
JAB ϭ 12.4 Hz, 1 H), 5.11 (d, JAB ϭ 12.4 Hz, 1 H), 5.77 (s, 1 H),
6.57 (s, 2 H), 7.65 (d, J ϭ 8.3 Hz, 2 H). Ϫ 13C NMR (75 MHz,
CDCl3): δ ϭ 17.5, 21.0, 65.9, 79.2, 105.3, 152.9, 172.1. Ϫ
C27H31NO8S (530.6): calcd. C 61.23, H 5.90, N 2.65; found C
61.04, H 5.98, N 2.52.
1
syn-rac-14 (selected signals): H NMR (300 MHz, CDCl3): δ ϭ
5.07 (s, 1 H), 5.82 (s, 1 H), 7.62 (d, J ϭ 8.3 Hz, 2 H).
Benzyl (±)-anti-3-(3,4-Dichlorophenyl)-3-hydroxy-2-methyl-2-
[(4-toluenesulfonyl)amino]propanoate (anti-rac-15): According to
the general procedure, the aldol reaction of N-(4-toluenesulfonyl)-
alanine benzyl ester (rac-2) (134 mg, 0.4 mmol) with 3,4-dichloro-
Benzyl (±)-3-Hydroxy-2-methyl-2-[(4-toluenesulfonyl)amino]-3-
benzaldehyde (84 mg, 0.48 mmol) yielded anti-rac-15 (132 mg, (2,4,6-trimethoxyphenyl)propanoate (rac-18): According to the gen-
65%) after flash chromatography (hexanes/ethyl acetate, 8:2) as a
colorless solid, which was crystallized from dichloromethane/hex-
eral procedure, the aldol reaction of N-(4-toluenesulfonyl)alanine
benzyl ester (rac-2) (134 mg, 0.4 mmol) with 2,4,6-trimethoxybenz-
414
Eur. J. Org. Chem. 1998, 409Ϫ417