6886 J . Org. Chem., Vol. 62, No. 20, 1997
Kirsten et al.
1
65%; oil; H NMR δ 0.95 (t, J ) 7.6 Hz, 3 H), 1.13 (d, J ) 6.2
1.7 Hz, 3 H), 1.74 (dq, J ) 13.9 Hz, J ) 7.6 Hz, 1 H), 1.86 (dq,
J ) 13.9 Hz, J ) 7.6 Hz, 1 H), 2.43 (s, 1 H), 5.47 (dq, J ) 15.5
Hz, J ) 1.7 Hz, 1 H), 6.14 (dq, J ) 6.6 Hz, J ) 15.5 Hz, 1 H);
13C{1H} NMR δ 8.4 (s), 17.4 (s), 30.3 (s), 73.2 (s), 120.0 (s),
129.9 (s), 130.2 (s); MS m/e (rel intensity) 125 (14, M+), 110
(8), 98 (15), 96 (66), 83 (19), 78 (30), 69 (43), 56 (43), 41 (100).
Hz, 3 H), 1.59 (m, 2 H), 1.86 (s, 3 H), 1.90-2.05 (m, 2 H), 2.61
(d, J ) 11.4 Hz, 3 H), 3.26 (dq, J ) 6.2 Hz, J ) 8.9 Hz, 1 H),
4.86 (dd, J ) 8.9 Hz, J ) 2.8 Hz, 1 H), 7.33-7.43 (m, 5 H);
31P{1H} NMR δ 17.41 (s); 13C{1H} NMR δ 13.7 (s), 15.5 (d, J )
10.3 Hz), 17.8 (s), 26.5 (s), 28.4 (s), 43.5 (d, J ) 6.3 Hz), 61.8
(d, J ) 12.1 Hz), 75.3 (d, J ) 8.4 Hz), 85.5 (s), 119.6 (s), 126.9
(s), 128.8 (s), 129.2 (s), 136.8 (d, J ) 6.2 Hz); IR 1270, 1185,
970 cm-1. Anal. Calcd for C16H23N2O3P: C, 59.62; H, 7.19; N,
8.69. Found: C, 59.54; H, 6.99; N, 8.48
(R)-2-Hydr oxy-2-ben zyl-3-pen ten on itr ile (6c): yield 64%;
1H NMR δ 1.75 (dd, J ) 6.6 Hz, J ) 1.7 Hz, 3 H), 3.05 (d, J )
13.7 Hz, 1 H), 3.08 (d, J ) 13.7 Hz, 1 H), 3.25 (s, 1 H), 5.55
(dq, J ) 15.4 Hz, J ) 1.7 Hz, 1 H), 6.07 (dq, J ) 15.4 Hz, J )
6.6 Hz, 1 H), 7.26-7.41 (m, 5 H); 13C{1H} NMR δ 17.4 (s), 47.2
(s), 72.3 (s), 119.8 (s), 127.8 (s), 128.5 (s), 129.4 (s), 130.0 (s),
130.7 (s), 133.4 (s); MS m/e (rel intensity) 187 (21, M+), 160
(16), 96 (24), 91 (100), 77 (15), 69 (50), 65 (30), 51 (26), 42 (14).
(1′R,2S,4S,5S)-2-(1′-Cyan o-1′-eth ylbu toxy)-3,4-dim eth yl-
5-p h en yl-1,3,2-oxa za p h osp h olid in -2-on e (5g): yield 71%;
mp 106-107 °C; H NMR δ 0.92 (t, J ) 7.3 Hz, 3 H), 1.07 (t,
1
J ) 7.3 Hz, 3 H), 1.12 (d, J ) 6.3 Hz, 3 H), 1.57 (m, 2 H),
1.92-2.07 (m, 2 H), 2.07 (dq, J ) 14.2 Hz, J ) 7.3 Hz, 1 H),
2.24 (dq, J ) 14.2 Hz, J ) 7.3 Hz, 1 H), 2.61 (d, J ) 11.4 Hz,
3 H), 3.29 (dq, J ) 6.3 Hz, J ) 8.9 Hz, 1 H), 4.85 (dd, J ) 8.9
Hz, J ) 2.8 Hz, 1 H), 7.33-7.42 (m, 5 H); 31P{1H} NMR δ 16.76
(s); 13C{1H} NMR δ 8.5 (s), 13.8 (s), 15.5 (d, J ) 10.1 Hz), 17.6
(s), 28.5 (d, J ) 3.1 Hz), 31.7 (s), 40.3 (d, J ) 4.9 Hz), 61.7 (d,
J ) 11.9 Hz), 80.0 (d, J ) 8.4 Hz), 85.6 (s), 118.9 (d, J ) 7.9
Hz), 127.0 (s), 128.7 (s), 129.2 (s), 136.7 (d, J ) 7.2 Hz); IR
1270, 1185, 985 cm-1. Anal. Calcd for C17H25N2O3P: C, 60.70;
H, 7.49; N, 8.33. Found: C, 60.72; H, 7.43; N, 8.15.
(R)-2-H yd r oxy-5-p h en yl-2-p r op -1′-en yl-4-p en t en on i-
tr ile (6d ): yield 59%; 1H NMR δ 1.77 (dd, J ) 6.6 Hz, J )1.7
Hz, 3 H), 2.70 (dd, J ) 14.0 Hz, J ) 7.9 Hz, 1 H), 2.74 (dd, J
) 14.0 Hz, J ) 6.8 Hz, 1 H), 3.68 (s, 1 H), 5.56 (dq, J ) 15.5
Hz, J ) 1.7 Hz, 1 H), 6.16 (dq, J ) 15.5 Hz, J ) 6.6 Hz, 1 H),
6.23 (ddd, J ) 15.8 Hz, J ) 7.9 Hz, J ) 6.8 Hz, 1 H), 6.58 (d,
J ) 15.8 Hz), 1 H), 7.20-7.47 (m, 5 H); 13C{1H} NMR δ 17.5
(s), 44.9 (s), 71.6 (s), 120.0 (s), 121.3 (s), 126.5 (s), 127.9 (s),
128.6 (s), 129.4 (s), 130.1 (s), 136.3 (s), 136.5 (s); MS m/e (rel
intensity) 213 (15, M+), 186 (20), 117 (100), 96 (22), 91 (56),
77 (46), 69 (72), 65 (69), 51 (61), 42 (22).
(1′S,2S,4S,5S)-2-(1′-Cyan o-1′-ben zylbu toxy)-3,4-dim eth yl-
5-p h en yl-1,3,2-oxa za p h osp h olid in -2-on e (5h ): yield 55%;
mp 90-91 °C; H NMR δ 0.97 (t, J ) 7.3 Hz, 3 H), 1.17 (d, J
(R)-2-Hyd r oxy-2-p r op -2′-en yl-3-p en ten on itr il (6e): yield
1
1
62%; H NMR δ 1.78 (dd, J ) 6.6 Hz, J ) 1.7 Hz, 3 H), 2.56
) 5.9 Hz, 3 H), 1.69 (m, 2 H), 1.94-2.13 (m, 2 H), 2.55 (d, J )
11.4 Hz, 3 H), 3.28 (dq, J ) 5.9 Hz, J ) 9.0 Hz, 1 H), 3.37 (d,
J ) 13.9 Hz, 1 H), 3.55 (d, J ) 13.9 Hz, 1 H), 4.89 (dd, J ) 9.0
Hz, J ) 2.2 Hz, 1 H), 7.27-7.43 (m, 10 H); 31P{1H} NMR δ
16.79 (s); 13C{1H} NMR 13.7 (s), 15.4 (d, J ) 10.2 Hz), 17.7
(s), 28.3 (d, J ) 3.4 Hz), 40.7 (d, J ) 4.4 Hz), 44.6 (s), 61.7 (d,
J ) 11.9 Hz), 79.0 (d, J ) 8.7 Hz), 85.7 (s), 118.8 (d, J ) 6.4
Hz), 127.0 (s), 127.7 (s), 128.5 (s), 128.7 (s), 129.2 (s), 130.9
(dt, J ) 7.2 Hz, J ) 1.1 Hz, 2 H), 4.09 (s, 1 H), 5.23-5.31 (m,
2 H), 5.51 (dq, J ) 15.4 Hz, J ) 1.7 Hz, 1 H), 5.86 (ddt, J )
16.8 Hz, J ) 10.5 Hz, J ) 7.2 Hz, 1 H), 6.11 (dq, J ) 15.4 Hz,
J ) 6.6 Hz, 1 H); 13C{1H} NMR δ 17.4 (s), 45.5 (s), 71.4 (s),
120.0 (s), 121.2 (s), 129.6 (s), 129.7 (s), 130.5 (s); MS m/e (rel
intensity) 137 (4, M+), 110 (4), 96 (100), 83 (15), 69 (72), 54
(43), 42 (94).
(s), 133.5 (s), 136.5 (d, J ) 6.4 Hz); IR 1270, 1185, 965 cm-1
Anal. Calcd for C22H27N2O3P: C, 66.32; H, 6.83; N, 7.03.
Found: C, 66.13; H, 7.12; N, 7.08.
.
(R)-2-Hyd r oxy-2-m eth ylp en ta n on itr ile (6f): yield 56%;
1H NMR δ 1.00 (t, J ) 7.3 Hz, 3 H), 1.56 (m, 2 H), 1.60 (s, 3
H), 1.75 (m, 2 H), 3.02 (s, 1 H); 13C NMR 13.8 (s), 17.6 (s), 27.6
(s), 43.7 (s), 68.6 (s), 122.0 (s); MS m/e (rel intensity) 98 (21,
M+ - CH3), 94 (10), 86 (9), 80 (28), 71 (56), 58 (10), 53 (18), 43
(100), 41 (90); the [MNH4]+ ion was detected via CI-MS.
(R)-2-Eth yl-2-h yd r oxyp en ta n on itr ile (6g): yield 50%; 1H
NMR δ 0.94 (t, J ) 7.3 Hz, 3 H), 1.06 (t, J ) 7.3 Hz, 3 H), 1.50
(m, 2 H), 1.67 (m, 2 H), 1.74 (m, 2 H), 2.27 (s, 1 H); 13C{1H}
NMR δ 8.2 (s), 11.4 (s), 18.8 (s), 33.3 (s), 41.8 (s), 72.9 (s), 121.1
(s); MS m/e (rel intensity) 108 (3), 100 (8, M+ - HCN), 98 (41),
85 (53), 80 (37), 70 (59), 57 (65), 53 (22), 43 (84), 41 (100); the
[MNH4]+ ion was detected via CI-MS.
(S)-2-Ben zyl-2-h yd r oxyp en ta n on itr ile (6h ): yield 50%;
1H NMR δ 0.95 (t, J ) 7.3 Hz, 3 H), 1.61 (m, 2 H), 1.76 (m, 2
H), 2.33 (s, 1 H), 2.87 (d, J ) 13.9 Hz, 1 H), 3.03 (d, J ) 13.9
Hz, 1 H), 7.33-7.41 (m, 5 H); 13C{1H} NMR δ 13.9 (s), 17.6
(s), 42.2 (s), 46.4 (s), 72.1 (s), 120.7 (s), 128.1 (s), 129.0 (s), 130.5
(s), 133.3 (s); MS m/e (rel intensity) 189 (40, M+), 162 (25), 91
(100), 77 (13), 71 (56), 65 (47), 51 (20), 43 (82), 41 (63).
(S)-2-H yd r oxy-5-p h en yl-2-p r op ylp en t a n on it r ile (6i):
yield 53%; 1H NMR δ 0.91 (t, J ) 7.3 Hz, 3 H), 1.49 (m, 4 H),
1.67 (m, 4 H), 1.83 (m, 2 H), 2.24 (s, 1 H), 7.15-7.31 (m, 5 H);
13C{1H} NMR δ 13.0 (s), 16.5 (s), 24.9 (s), 34.8 (s), 39.1 (s),
41.8 (s), 72.1 (s), 121.8 (s), 126.8 (s), 129.0 (s), 129.2 (s), 142.0
(s); MS m/e (rel intensity) 217 (3, M+), 190 (39), 175 (51), 147
(32), 129 (17), 119 (22), 104 (100), 99 (9), 91 (70), 86 (25), 77
(29), 71 (35), 65 (41), 58 (48), 51 (20), 43 (73), 41 (80).
Gen er a l P r oced u r e for th e Hyd r ogen a tion of Ter tia r y
Olefin ic Cya n oh yd r in s 6a -d . The olefinic cyanohydrins
were dissolved in ethanol (ca. 25 mg/mL) and stirred with a
catalytic amount of palladium on carbon under a hydrogen
atmosphere for 36 h at room temperature. Filtration and
evaporation yielded the crude aliphatic cyanohydrins 6f-i
(95%).
Gen er a l P r oced u r e for th e P r ep a r a tion of th e r-Hy-
d r oxy Acid s 8a ,b. The cyanohydrins were stirred with concd
HCl (2.5 mL/mmol cyanohydrin) for 16 h, then heated under
reflux for 5 h. After extraction with diethyl ether, the collected
organic layers were dried (MgSO4) and evaporated. The
(1′S,2S,4S,5S)-2-(1′-Cya n o-4′-p h en yl-1′-p r op ylbu toxy)-
3,4-dim eth yl-5-ph en yl-1,3,2-oxazaph osph olidin -2-on e (5i):
yield 56%; oil: 1H NMR δ 0.97 (t, J ) 7.6 Hz, 3 H), 1.19 (d, J
) 6.0 Hz, 3 H), 1.59 (m, 2 H), 1.93 (m, 2 H), 1.93-2.12 (m, 2
H), 2.12-2.27 (m, 2 H), 2.64 (d, J ) 11.4 Hz, 3 H), 2.68 (m, 2
H), 3.32 (dq, J ) 6.0 Hz, J ) 8.8 Hz, 1 H), 4.90 (dd, J ) 8.8
Hz, J ) 2.5 Hz, 1 H), 7.14-7.39 (m, 10 H); 31P{1H} NMR δ
16.78 (s); 13C{1H} NMR δ 13.7 (C1, s), 15.5 (d, J ) 9.8 Hz),
17.6 (s), 26.0 (s), 28.5 (d, J ) 2.8 Hz), 35.3 (s), 38.1 (s), 40.8 (d,
J ) 4.9 Hz), 61.7 (d, J ) 11.7 Hz), 79.1 (d, J ) 8.6 Hz), 85.6
(s), 118.9 (d, J ) 7.2 Hz), 126.0 (s), 127.0 (s), 128.3 (s), 128.4
(s), 128.8 (s), 129.3 (s), 136.7 (d, J ) 6.3 Hz), 141.3 (s); IR 1270,
1185, 970 cm-1
7.33; N, 6.57. Found: C, 67.78; H, 7.39; N, 6.76.
. Anal. Calcd for C24H31N2O3P: C, 67.59; H,
Gen er a l P r oced u r e for th e Clea va ge of 5a -i to Keton e
Cya n oh yd r in s 6a -i. Under a nitrogen atmosphere the
cyanohydrin phosphates were dissolved in freshly dried THF
(ca. 25 mg/mL), then titanium chloride triisopropoxide (1.0 M
solution in hexane, 4 equiv) was added at room temperature.
The mixture was stirred for 4 h at room temperature, water
was added under a nitrogen atmosphere, and the two-layer
system was vigorously stirred for another 4 h at room
temperature. After phase separation, drying over magnesium
sulfate, and evaporation of the solvent, the free tertiary
cyanohydrins can be chromatographed over silica gel, but
cleavage to the parent ketone must be considered. The crude
product can also be used for further syntheses. As already
described by us,17 1 can be reobtained from the aqueous layer
by acid hydrolysis.
(R)-2-Hyd r oxy-2-m et h yl-3-p en t en on it r ile (6a ): yield
56%; 1H NMR δ 1.63 (s, 3 H), 1.77 (dd, J ) 6.6 Hz, J ) 1.7 Hz,
3 H), 4.10 (s, 1 H), 5.55 (dq, J ) 15.4 Hz, J ) 1.7 Hz, 1 H),
6.08 (dq, J ) 15.4 Hz, J ) 6.6 Hz, 1 H); 13C{1H} NMR δ 17.3
(s), 28.5 (s), 68.1 (s), 121.2 (s), 128.2 (s), 131.4 (s); MS m/e (rel
intensity) 111 (12, M+), 96 (100), 84 (11), 78 (41), 69 (60), 42
(43).
(R)-2-Hyd r oxy-2-eth yl-3-p en ten on itr ile (6b): yield 60%;
1H NMR δ 0.99 (t, J ) 7.6 Hz, 3 H), 1.73 (dd, J ) 6.6 Hz, J )