Diastereoselective Synthesis of Hydroxyphosphonic Acids
FULL PAPER
C), 138.6, 140.8 (d, JC,P = 16.9 Hz, C) ppm. IR (KBr): ν = 3424,
˜
31P NMR (CDCl3): δ = 27.4 ppm. 13C NMR (CDCl3): δ = 21.6,
2
3
22.5, 25.8, 26.1, 30.6, 33.7, 41.2 (d, JC,P = 6.7 Hz), 46.2, 49.5 (d, 3271, 1159, 1023, 889 cm–1. MS (EI): m/z (%) = 539 (1) [M]+, 397
3JC,P = 6.9 Hz), 58.3 (d, 1JC,P = 121.1 Hz), 60.4, 72.9, 75.9 (d, 2JC,P (38), 302 (17), 261 (16), 260 (100), 91 (50), 57 (21), 55 (20).
= 7.8 Hz), 126.0 (2 C), 126.7 (2 C), 127.0, 127.4 (4 C), 127.7 (2 C),
(1S,2R)-2-[(2R,4aS,7R,8aR)-3-Benzyl-4,4,7-trimethyl-2-oxooctahy-
dro-2H-1,3,2-benzoxazaphosphinin-2-yl]-1-(4-chlorophenyl)-2-phen-
ylethanol (syn-14e): White solid, m.p. 254–255 °C (hexane/EtOAc).
Rf = 0.10 (hexane/EtOAc, 2:1). [α]2D3 = –19.4 (c = 0.75, CHCl3). 1H
NMR (CDCl3): δ = 0.50–0.74 (m, 2 H), 0.80 (d, J = 6.5 Hz, 3 H),
0.92–0.97 (m, 1 H), 1.00 (s, 3 H), 1.05–1.34 (m, 2 H), 1.27 (s, 3 H),
3
128.4 (2 C), 131.2 (d, JC,P = 6.9 Hz, 2 C), 133.4, 140.6, 141.4 (d,
3JC,P = 15.1 Hz) ppm. IR (KBr): ν = 3422, 1162, 1055, 1040,
˜
884 cm–1. C31H38NO3P (503.61): calcd. C 73.93, H 7.61, N 2.78;
found C 73.80, H 7.50, N 2.65.
(1R,2R)-2-[(2R,4aS,7R,8aR)-3-Benzyl-4,4,7-trimethyl-2-oxoocta-
hydro-2H-1,3,2-benzoxazaphosphinin-2-yl]-1-(4-methoxyphenyl)-2-
phenylethanol (anti-13e): White solid, m.p. 184–185 °C (hexane/
EtOAc). Rf = 0.64 (hexane/EtOAc, 1:1). [α]2D3 = –25.7 (c = 0.95,
2
1.57–1.66 (m, 2 H), 1.80–1.95 (m, 1 H), 3.00 (dd, JH,P = 19.4 Hz,
3
J = 2.7 Hz, 1 H), 4.24 (tdd, J1 = 10.7 Hz, J2 = 4.8 Hz, JH,P
=
3
1.7 Hz, 1 H), 4.43 (dd, J = 16.5 Hz, JH,P = 11.3 Hz, 1 H), 4.67
(dd, J = 16.5 Hz, JH,P = 12.5 Hz, 1 H), 4.90 (d, J = 2.4 Hz, 1 H),
3
1
CHCl3). H NMR (CDCl3): δ = 0.17–0.26 (m, 1 H), 0.47–0.52 (m,
3
5.26 (ddd, JH,P = 8.4 Hz, J1 = 2.7 Hz, J2 = 2.4 Hz, 1 H), 6.78–
1 H), 0.85–0.93 (m, 1 H), 0.92 (d, J = 6.5 Hz, 3 H), 0.97 (s, 3 H),
7.54 (m, 14 H) ppm. 31P NMR (CDCl3): δ = 27.2 ppm. 13C NMR
0.97–1.09 (m, 1 H), 1.03 (s, 3 H), 1.22–1.30 (m, 1 H), 1.31–1.45 (m,
3
(CDCl3): δ = 21.6, 22.3, 26.0, 26.1, 30.6, 33.7, 41.1 (d, JC,P
=
2
1 H), 1.49–1.55 (m, 1 H), 2.08–2.12 (m, 1 H), 2.79 (dd, JH,P
=
3
1
6.5 Hz), 46.1, 49.5 (d, JC,P = 6.9 Hz), 57.8 (d, JC,P = 121.5 Hz),
16.9 Hz, J = 10.0 Hz, 1 H), 3.65 (s, 3 H), 4.26 (td, J1 = 10.7 Hz, J2
60.4, 72.5, 76.0 (d, 2JC,P = 8.0 Hz), 126.9, 127.1, 127.4 (2 C), 127.6
3
= 5.0 Hz, 1 H), 4.35 (dd, J = 15.4 Hz, JH,P = 9.0 Hz, 1 H), 4.48
(4 C), 127.9 (2 C), 128.4 (2 C), 131.2 (d, 3JC,P = 6.9 Hz, 2 C), 132.3,
(dd, 3JH,P ≈ J = 15.4 Hz, 1 H), 5.19 (dd, 3JH,P ≈ J = 10.0 Hz, 1 H),
6.31 (s, 1 H), 6.55–7.65 (m, 14 H) ppm. 31P NMR (CDCl3): δ =
28.7 ppm. 13C NMR (CDCl3): δ = 21.8, 22.1, 25.6, 25.7, 30.7, 33.6,
41.1 (d, 3JC,P = 7.4 Hz), 46.3, 47.8, 54.9 (d, 1JC,P = 121.9 Hz), 54.9,
3
133.2, 140.0, 140.4 (d, JC,P = 15.2 Hz) ppm. IR (KBr): ν = 3420,
˜
1162, 1052, 1036, 880 cm–1. C31H37ClNO3P (538.06): calcd. C
69.20, H 6.93, N 2.60; found C 69.33, H 7.05, N 2.51.
2
(1R,2R)-1-[(2R,4aS,7R,8aR)-3-Benzyl-4,4,7-trimethyl-2-oxooctahy-
dro-2H-1,3,2-benzoxazaphosphinin-2-yl]-4-methyl-1-phenylpentan-2-
ol (anti-15e): White solid, m.p. 256–257 °C (hexane/EtOAc). Rf =
0.93 (hexane/EtOAc, 1:1). [α]2D3 = –35.7 (c = 0.89, CHCl3). 1H
NMR (CDCl3): δ = 0.14–0.23 (m, 1 H), 0.43–0.65 (m, 1 H), 0.73
(d, J = 6.8 Hz, 3 H), 0.81 (d, J = 6.5 Hz, 3 H), 0.85–1.17 (m, 3 H),
0.89 (s, 3 H), 0.90 (d, J = 5.7 Hz, 3 H), 0.96–1.03 (m, 1 H), 1.00
(s, 3 H), 1.22–1.31 (m, 2 H), 1.49–1.54 (m, 1 H), 1.78–1.90 (m, 1
60.2, 73.3, 75.5 (d, JC,P = 8.8 Hz), 113.0 (2 C), 126.7 (2 C), 127.6
(2 C), 128.2 (2 C), 128.5 (2 C), 129.7 (2 C), 130.8 (2 C), 134.4 (d,
3
3JC,P = 16.9 Hz), 135.4, 138.9 (d, JC,P = 15.1 Hz), 158.4 ppm. IR
(KBr): ν = 3421, 3291, 1192, 1026, 890 cm–1. MS: m/z (%) = 533
˜
(3) [M+], 397 (39), 382 (26), 302 (97), 260 (100), 135 (26), 91 (95).
(1S,2R)-2-[(2R,4aS,7R,8aR)-3-Benzyl-4,4,7-trimethyl-2-oxoocta-
hydro-2H-1,3,2-benzoxazaphosphinin-2-yl]-1-(4-methoxyphenyl)-2-
phenylethanol (syn-13e): White solid, m.p. 221–222 °C (hexane/
EtOAc). Rf = 0.42 (hexane/EtOAc, 1:1). [α]2D3 = –46.1 (c = 0.25,
2
H), 2.03–2.07 (m, 1 H), 2.55 (dd, JH,P = 16.5 Hz, J = 10.1 Hz, 1
H), 4.20 (td, J1 = 10.7 Hz, J2 = 4.9 Hz, 1 H), 4.30 (dd, J = 15.5 Hz,
1
3
3JH,P = 9.7 Hz, 1 H), 4.30–4.39 (m, 1 H), 4.47 (dd, JH,P ≈ J =
CHCl3). H NMR (CDCl3): δ = 0.56–0.76 (m, 2 H), 0.81 (d, J =
6.5 Hz, 3 H), 0.88–1.11 (m, 2 H), 0.97 (s, 3 H), 1.19–1.40 (m, 1 H),
15.5 Hz, 1 H), 5.80 (d, J = 0.7 Hz, 1 H), 7.18–7.69 (m, 10 H) ppm.
31P NMR (CDCl3): δ = 29.3 ppm. 13C NMR (CDCl3): δ = 21.1,
21.8, 22.2, 23.9 (2 C), 25.4 (d, 3JC,P = 3.9 Hz), 25.6, 30.7, 33.6, 41.0
2
1.28 (s, 3 H), 1.58–1.85 (m, 3 H), 3.06 (dd, JH,P = 18.8 Hz, J =
2.6 Hz, 1 H), 3.71 (s, 3 H), 4.24 (td, J1 = 9.2 Hz, J2 = 4.7 Hz, 1
3
3
2
2
H), 4.38 (dd, J = 16.5 Hz, JH,P = 11.6 Hz, 1 H), 4.70 (dd, J =
(d, JC,P = 7.4 Hz), 44.9 (d, JC,P = 14.5 Hz), 46.1 (d, JC,P
=
3
3
1
16.5 Hz, JH,P = 11.5 Hz, 1 H), 4.76 (s, 1 H), 5.28–5.30 (m, 1 H),
5.4 Hz), 47.9 (d, JC,P = 4.9 Hz), 54.0 (d, JC,P = 123.6 Hz), 60.0,
68.0 (d, JC,P = 4.7 Hz), 75.4 (d, JC,P = 8.7 Hz), 126.9 (d, JC,P
3.5 Hz), 127.4, 127.9 (d, JC,P = 2.4 Hz, 2 C), 128.3 (2 C), 129.2 (2
6.63–6.84 (m, 4 H), 7.10–7.59 (m, 10 H) ppm. 31P NMR (CDCl3):
δ = 27.5 ppm. 13C NMR (CDCl3): δ = 21.6, 22.5, 25.8, 26.1, 30.6,
2
2
5
=
4
1
3
33.7, 41.3, 46.2, 49.6, 55.1, 58.4 (d, JC,P = 120.4 Hz), 60.4, 72.7,
C), 130.5 (d, JC,P = 6.0 Hz, 2 C), 136.2, 139.0 ppm. IR (KBr): ν
˜
= 3424, 3300, 1184, 1066, 1026, 874 cm–1. C29H42NO3P (483.62):
calcd. C 72.02, H 8.75, N 2.90; found C 72.16, H 8.63, N 3.02.
76.0, 112.9 (2 C), 126.8 (2 C), 127.3 (2 C), 127.5 (2 C), 127.7 (2 C),
3
128.4 (2 C), 131.3 (2 C), (d, JC,P = 6.8 Hz), 133.6 (2 C), 140.8,
158.4 ppm. IR (KBr): ν = 3436, 1163, 1054, 1037, 880 cm–1
.
˜
(1S,2R)-1-[(2R,4aS,7R,8aR)-3-Benzyl-4,4,7-trimethyl-2-oxooctahy-
dro-2H-1,3,2-benzoxazaphosphinin-2-yl]-4-methyl-1-phenylpentan-2-
ol (syn-15e): White solid, m.p. 202–204 °C (hexane/EtOAc). Rf =
0.41 (hexane/EtOAc, 1:1). [α]2D3 = –64.2 (c = 0.37, CHCl3). 1H
NMR (CDCl3): δ = 0.66–0.75 (m, 1 H), 0.77 (d, J = 6.6 Hz, 3 H),
0.80 (d, J = 6.7 Hz, 3 H), 0.85 (d, J = 6.5 Hz, 3 H), 0.93 (s, 3 H),
0.96–1.12 (m, 2 H), 1.15 (s, 3 H), 1.20–1.32 (m, 3 H), 1.57–1.70 (m,
C32H40NO4P (533.64): calcd. C 72.02, H 7.56, N 2.62; found C
72.18, H 7.43, N 2.76.
(1R,2R)-2-[(2R,4aS,7R,8aR)-3-Benzyl-4,4,7-trimethyl-2-oxoocta-
hydro-2H-1,3,2-benzoxazaphosphinin-2-yl]-1-(4-chlorophenyl)-2-
phenylethanol (anti-14e): White solid, m.p. 227–228 °C (hexane/
EtOAc). Rf = 0.35 (hexane/EtOAc, 2:1). [α]2D3 = –10.2 (c = 0.98,
2
1
4 H), 1.88–1.92 (m, 1 H), 2.85 (dd, JH,P = 20.4 Hz, J = 2.6 Hz, 1
CHCl3). H NMR (CDCl3): δ = 0.14–0.23 (m, 1 H), 0.42–0.55 (m,
H), 4.09 (d, J = 2.4 Hz, 1 H), 4.18–4.33 (m, 2 H), 4.32 (dd, J =
1 H), 0.70–0.97 (m, 1 H), 0.91 (d, J = 6.5 Hz, 3 H), 0.98 (s, 3 H),
3
3
16.5 Hz, JH,P = 11.4 Hz, 1 H), 4.62 (dd, J = 16.5 Hz, JH,P
=
1.02 (s, 3 H), 1.06–1.19 (m, 1 H), 1.28–1.39 (m, 1 H), 1.40–1.46 (m,
11.6 Hz, 1 H), 7.21–7.49 (m, 10 H) ppm. 31P NMR (CDCl3): δ =
2
1 H), 1.50–1.58 (m, 1 H), 2.04–2.13 (m, 1 H), 2.63 (dd, JH,P
=
28.0 ppm. 13C NMR (CDCl3): δ = 21.7, 22.1, 22.5, 23.2, 24.4, 25.7,
17.1 Hz, J = 10.5 Hz, 1 H), 4.27 (td, J1 = 10.7 Hz, J2 = 4.9 Hz, 1
3
3
3
26.0, 30.7, 33.8, 41.3 (d, JC,P = 6.8 Hz), 43.8 (d, JC,P = 12.6 Hz),
46.1, 49.3 (d, 3JC,P = 6.2 Hz), 55.3 (d, 1JC,P = 123.0 Hz), 60.1, 69.0,
75.7 (d, 2JC,P = 8.2 Hz), 126.9, 127.0, 127.8 (2 C), 127.9 (2 C), 128.3
H), 4.35 (dd, J = 15.3 Hz, JH,P = 9.0 Hz, 1 H), 4.44 (dd, JH,P
=
=
3
15.3 Hz, JH,H = 15.2 Hz, 1 H), 5.17 (dd, J = 10.5 Hz, JH,P
8.8 Hz, 1 H), 6.50 (s, 1 H), 6.86–7.63 (m, 14 H) ppm. 31P NMR
3
(CDCl3): δ = 28.4 ppm. 13C NMR (CDCl3): δ = 21.8, 21.9, 25.8 (2
(2 C), 131.1 (d, JC,P = 6.7 Hz, 2 C), 134.6, 140.4 ppm. IR (KBr):
ν = 3411, 1196, 1050, 1030, 874 cm–1. C H NO P (483.62): calcd.
3
2
˜
29 42
3
C), 30.7, 33.6, 41.1 (d, JC,P = 7.4 Hz), 46.3 (d, JC,P = 4.5 Hz),
47.8 (d, 3JC,P = 4.7 Hz), 54.9 (d, JC,P = 122.5 Hz), 60.3, 73.2, 75.6
1
C 72.02, H 8.75, N 2.90; found C 72.14, H 8.90, N 2.99.
2
2
(d, JC,P = 8.9 Hz), 127.0, 127.6 (2 C), 127.7 (6 C), 128.5 (d, JC,P
= 4.4 Hz, 2 C), 129.9 (2 C), 130.8, 132.5, 134.7 (d, JC,P = 7.4 Hz,
(1S,2S)-1-[(2S,4aS,7R,8aR)-3-Benzyl-4,4,7-trimethyl-2-oxooctahy-
dro-2H-1,3,2-benzoxazaphosphinin-2-yl]-4-methyl-1-phenylpentan-2-
3
Eur. J. Org. Chem. 2007, 3012–3022
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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