A Versatile Route to syn- and anti-α-Amino β-Hydroxy Esters
FULL PAPER
a slightly yellow powder (125 mg, 90% yield over two steps); purifi-
ppm. 13C NMR (CDCl3, 75 MHz): δ ϭ 14.1, 22.7, 25.7, 29.7, 31.9,
cation by silica gel column chromatography (cyclohexane/ethyl 33.4, 52.7, 58.1, 73.3, 127.2, 128.7, 130.1, 132.1, 167.9, 171.0 ppm.
acetate, 7:3). Physical data identical to those of (2S,3S)-5a. [α]D21
Ϫ32 (c ϭ 1.0, CHCl3). HPLC: Chiralcel OD-H, hexane/2-propanol
(85:15), 0.5 mL/min, λ ϭ 254 nm, tR 12.59 min.
ϭ
MS (DCI, NH3): m/z (%) ϭ 434 (100) [M ϩ H]ϩ ppm. HRMS
(DCIϩ): m/z calcd. for C26H44NO4: 434.3270; found 434.3264.
[α]2D1 ϭ ϩ19 (c ϭ 0.8, CHCl3). HPLC: Chiralpak AS-H, hexane/2-
propanol (98:2), 1.0 mL/min, λ ϭ 254 nm, tR 32.31 min.
Methyl (2S,3S)-2-Benzoylamino-7-benzyloxy-3-hydroxyheptanoate
[(2S,3S)-5b]: This compound was obtained from 4b (0.5 mmol,
158 mg) by the General Procedure, by treatment with [Ru(S)-SYN-
PHOSBr2], as a brown solid (182 mg, 94% yield over two steps);
purification by silica gel column chromatography (cyclohexane/
ethyl acetate, 6:4). Physical data identical to those of (2R,3R)-5b.
[α]2D1 ϭ ϩ26 (c ϭ 1.0, CHCl3). HPLC Chiralcel OD-H, hexane/2-
propanol (95:5), 1 mL/min, λ ϭ 254 nm, tR 75.68 min.
Methyl (2R,3R)-2-Benzoylamino-3-hydroxyoctadecanoate [(2R,3R)-
5d]: This compound was obtained from 4d (0.5 mmol, 182 mg) by
the General Procedure, by treatment with [Ru(R)-SYNPHOSBr2],
as a slightly brown solid (185 mg, 85% yield over two steps); purifi-
cation by silica gel column chromatography (cyclohexane/ethyl
acetate, 8:2). Physical data identical to those of (2S,3S)-5d. [α]D21
ϭ
Ϫ22 (c ϭ 0.8, CHCl3). HPLC: Chiralpak AS-H, hexane/2-propa-
nol, (98:2), 1.0 mL/min, λ ϭ 254 nm, tR ϭ 26.37 min.
Methyl (2R,3R)-2-Benzoylamino-7-benzyloxy-3-hydroxyheptanoate
[(2R,3R)-5b]: This compound was obtained from 4b (0.5 mmol,
158 mg) by the General Procedure, by treatment with [Ru(R)-SYN-
PHOSBr2], as a brown solid (179 mg, 93% yield over two steps);
purification by silica gel column chromatography (cyclohexane/
Ethyl
(2S,3S)-2-Benzoylamino-3-hydroxy-4-methylpentanoate
[(2S,3S)-5e]: This compound was obtained from 4e (0.5 mmol,
105 mg) by the General Procedure, by treatment with [Ru(S)-SYN-
PHOSBr2], as a brown solid (125 mg, 90% yield over two steps);
purification by silica gel column chromatography (cyclohexane/
ethyl acetate, 8:2). Physical data identical to those of (2R,3R)-5e.
[α]2D1 ϭ ϩ33 (c ϭ 1.0, CHCl3). HPLC: Chiralcel OJ, hexane/2-pro-
panol (96:04), 1.0 mL/min, λ ϭ 254 nm, tR 19.31 min.
1
ethyl acetate, 6:4). M.p. 42 °C. H NMR (CDCl3, 300 MHz): δ ϭ
1.57 (m, 6 H), 3.46 (t, J ϭ 6.1 Hz, 2 H), 3.77 (s, 3 H), 4.04 (m, 1
H, CHOH), 4.48 (s, 2 H), 4.87 (dd, J ϭ 3.2, 7.3 Hz, 1 H, CHNH),
7.28 (m, 5 H), 7.42 (t, J ϭ 7.0 Hz, 2 H), 7.51 (t, J ϭ 7.2 Hz, 1 H),
7.82 (d, J ϭ 7.0 Hz, 2 H) ppm. 13C NMR (CDCl3, 75 MHz): δ ϭ
22.5, 29.4, 33.1, 52.6, 58.0, 70.1, 72.8, 3.0, 127.2, 127.5, 127.6,
128.3, 128.6, 131.9, 133.3, 138.4, 167.8, 170.9 ppm. MS (DCI,
NH3): m/z (%) ϭ 386 (100) [M ϩ H]ϩ ppm. HRMS (DCIϩ): m/z
calcd. for C22H28NO5: 386.1967; found 386.1971. [α]2D1 ϭ Ϫ28 (c ϭ
1.0, CHCl3). HPLC Chiralcel OD-H, hexane/2-propanol (95:5),
1 mL/min, λ ϭ 254 nm, tR 50.89 min.
Ethyl
(2R,3R)-2-Benzoylamino-3-hydroxy-4-methylpentanoate
[(2R,3R)-5e]: This compound was obtained from 4e (0.5 mmol,
105 mg) by the General Procedure, by treatment with [Ru(R)-SYN-
PHOSBr2], as a brown solid (135 mg, 96% yield over two steps);
purification by silica gel column chromatography (cyclohexane/
1
ethyl acetate, 8:2). M.p. 86 °C. H NMR (CDCl3, 300 MHz): δ ϭ
1.03 (d, J ϭ 6.6 Hz, 3 H), 1.06 (d, J ϭ 6.6 Hz, 3 H), 1.34 (t, J ϭ
7.2 Hz, 3 H), 1.79 (m, 1 H), 3.63 (dd, J ϭ 3.2, 8.7 Hz, 1 H, CHOH),
4.28 (dq, J ϭ 1.9, 7.2 Hz, 2 H), 4.93 (dd, J ϭ 3.1, 7.2 Hz, 1 H,
CHNH), 7.20 (br. d, J ϭ 7.2 Hz, 1 H, NH), 7.47 (m, 3 H), 7.82
(m, 2 H) ppm. 13C NMR (CDCl3, 75 MHz): δ ϭ 14.1, 19.0, 31.6,
56.2, 61.9, 78.9, 127.1, 128.6, 131.9, 133.5, 167.5, 171.0 ppm. MS
(DCI, NH3): m/z (%) ϭ 280 (100) [M ϩ H]ϩ ppm. HRMS (DCIϩ):
m/z calcd. for C15H22NO4: 280.1549; found 280.1551. [α]2D1 ϭ Ϫ36
(c ϭ 1.0, CHCl3). HPLC: Chiralcel OJ, hexane/2-propanol (96:4),
1.0 mL/min, λ ϭ 254 nm, tR 15.82 min.
Methyl (2S,3S)-2-Benzoylamino-3-hydroxyoctanoate [(2S,3S)-5c]:
This compound was obtained from 4c (0.5 mmol, 112 mg) by the
General Procedure, by treatment with [Ru(S)-SYNPHOSBr2], as
a brown solid (124 mg, 85% yield over two steps); purification by
silica gel column chromatography (cyclohexane/ethyl acetate, 7:3).
Physical data identical to those of (2R,3R)-5c. [α]2D1 ϭ ϩ26 (c ϭ
1.0, CHCl3). HPLC: Chiralpak AS-H, hexane/2-propanol (98:2),
1.0 mL/min, λ ϭ 254 nm, tR 66.29 min.
Methyl (2R,3R)-2-Benzoylamino-3-hydroxyoctanoate [(2R,3R)-5c]:
This compound was obtained from 4c (0.5 mmol, 112 mg) by the
General Procedure, by treatment with [Ru(R)-SYNPHOSBr2], as
a brown solid (132 mg, 90% yield over two steps); purification by
silica gel column chromatography (cyclohexane/ethyl acetate, 7:3).
M.p. 60 °C. 1H NMR (CDCl3, 300 MHz): δ ϭ 0.87 (t, J ϭ 6.7 Hz,
3 H), 1.28 (m, 4 H), 1.49 (m, 4 H), 3.80 (s, 3 H), 4.04 (m, 1 H,
CHOH), 4.88 (dd, J ϭ 3.2, 7.3 Hz, 1 H, CHNH), 7.24 (br. d, J ϭ
7.3 Hz, 1 H, NH), 7.46 (m, 3 H), 7.82 (d, J ϭ 6.4 Hz, 2 H) ppm.
13C NMR (CDCl3, 75 MHz): δ ϭ 14.0, 22.5, 25.3, 31.5, 33.4, 52.7,
58.0, 73.2, 127.2, 128.6, 131.9, 133.3, 167.9, 171.0 ppm. MS (DCI,
NH3): m/z (%) ϭ 311 (2) [M ϩ NH4]ϩ, 294 (100) [M ϩ H]ϩ ppm.
HRMS (DCIϩ): m/z calcd. for C16H24NO4: 294.1705; found
294.1711. [α]2D1 ϭ Ϫ27 (c ϭ 1.0, CHCl3). HPLC: Chiralpak AS-H,
hexane/2-propanol (98:2), 1.0 mL/min, λ ϭ 254 nm, tR 50.83 min.
Acknowledgments
A
fellowship from the C.N.R.S./D.G.A. (C.M.) is gratefully
acknowledged. We also thank Dr. P. Dellis and Dr. N. Champion
(SYNKEM S. A. S.) for financial support.
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the General Procedure, by treatment with [Ru(S)-SYNPHOSBr2],
as a slightly brown solid (180 mg, 83% yield over two steps); purifi-
cation by silica gel column chromatography (cyclohexane/ethyl
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acetate, 8:2). M.p. 87 °C. H NMR (CDCl3, 300 MHz): δ ϭ 0.88
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(t, J ϭ 6.7 Hz, 3 H), 1.25 (br. s, 26 H), 1.50 (m, 2 H), 3.83 (s, 3 H),
4.05 (m, 1 H, CHOH), 4.89 (dd, J ϭ 3.1, 6.9 Hz, 1 H, CHNH),
7.15 (br. d, J ϭ 6.9 Hz, 1 H, NH), 7.50 (m, 3 H), 7.84 (m, 2 H)
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