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4.9.1.
phenyl]-ethyl-2-methyl-1,3-dioxolane
the general procedure for protection of ketones 12, b-
aminoketone 12a (0.35 g) afforded, after purification
on silica gel (ethyl acetate/cyclohexane 1:3), ketopro-
(ꢀ)-(20S)-2-[20-(N-Benzyloxycarbonylamino)-20-
gel (ethyl acetate/cyclohexane 1:3), ketoprotected ad-
25
13a. Following
duct (ꢀ)-13d as a yellow oil (0.50 g, 54%): ½a ¼ ꢀ3:6
D
1
(c 1.32, CHCl3); H NMR (400 MHz, CDCl3) d 7.40–
7.28 (5H, m, Ph), 5.36 (1H, br s, NH), 5.12 (2H, m,
OCH2Ph), 4.00–3.80 (5H, m, C(4)H2, C(5)H2 and
C(20)H), 1.76 (2H, m, C(10)H2), 1.60(2H, m,
C(2)CH2C3H7), 1.40–1.28 (4H, m, C(2)CH2C2H4CH3),
1.24 (3H, d, J = 6.4 Hz, C(30)H3), 0.91 (3H, t,
J = 7.1 Hz, C(2)C3H6CH3); 13C NMR (100 MHz,
CDCl3) d 155.9, 136.9, 128.4, 128.0, 127.9, 111.0, 66.3,
65.0, 64.5, 43.9, 43.1, 42.7, 37.14, 25.9, 22.9, 22.3, 14.0;
IR (neat) m 3344, 3032, 2955, 2872, 1720, 1512, 1454,
1375, 1340, 1238, 1157, 1090; HR-ESI-MS calculated
for: C18H28NO4 (M+H)+ 322.2018, found 322.2017.
tected adduct (ꢀ)-13a as a colourless oil (0.24 g, 60%):
25
½a ¼ ꢀ11:4 (c 1.32, CHCl3); 1H NMR (400 MHz,
D
CDCl3) d 7.40–7.26 (10H, m, Ph), 6.00 (1H, d,
J = 3.9 Hz, NH), 5.13 (1H, d, J = 12.3 Hz, OCH2Ph),
5.06 (1H, d, J = 12.3 Hz, OCH2Ph), 4.90(1H, m,
C(20)H), 4.90–3.88 (4H, m, C(4)H2 and C(5)H2), 2.11–
2.09 (2H, m, C(10)H2), 1.36 (3H, s, C(2)Me); 13C
NMR (100 MHz, CDCl3) d 155.7, 140.1, 136.6, 128.6,
128.4, 128.3, 127.9, 126.9, 125.8, 109.0, 66.4, 64.8,
64.1, 52.2, 45.2, 24.0; IR (neat) m 3346, 3060, 3033,
2983, 2882, 1685, 1534, 1496, 1450, 1373, 1253, 1043;
HR-ESI-MS calculated for: C20H24NO4 (M+H)+
342.1705, found 342.1696.
4.9.5.
(+)-(20R)-2-methyl-2-(20-N-benzyloxycarbonyl-
amino)-pentyl-1,3-dioxolane 13e. Following the general
procedure for protection of ketones 12, b-aminoketone
12e (1.10g) afforded, after purification on silica gel
4.9.2.
(ꢀ)-(20S)-2-Benzyl-2-[20-(N-benzyloxycarbonyl-
(ethyl acetate/cyclohexane 1:6), ketoprotected adduct
25
amino)-20-phenyl]-ethyl-1,3-dioxolane 13b. Following
the general procedure for protection of ketones 12, b-
aminoketone 12b (0.60 g) afforded, after purification
on silica gel (ethyl acetate/cyclohexane 1:4), ketopro-
(+)-13e as a yellow oil (0.65 g, 54%): ½a ¼ þ2:2 (c
D
1.08, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.38–
7.30(5H, m, Ph), 5.11 (3H, m NH and OCH2Ph),
3.98–3.82 (5H, m, C(4)H2, C(5)H2 and C(20)H), 1.87
(1H, br d, J = 14.6 Hz, C(10)HA), 1.75 (1H, dd,
J = 14.6 and 9.3 Hz, C(10)HB), 1.54–1.45 (2H, m,
C(30)H2), 1.40–1.25 (5H, m, C(40)H2 and C(1)Me),
0.92 (3H, t, J = 7.2 Hz, C(50)H3); 13C NMR
(100 MHz, CDCl3) d 156.0, 136.9, 128.4, 128.0, 127.5,
109.4, 66.3, 64.7, 64.1, 47.8, 42.9, 38.4, 24.0, 18.8, 14.0;
IR (neat) m 3338, 3033, 2958, 2934, 2874, 1704, 1537,
1455, 1379, 1253, 1102; HR-ESI-MS calculated for:
C17H26NO4 (M+H)+ 308.1862, found 308.1858.
tected adduct (ꢀ)-13b as a white solid (0.30 g, 50%):
25
mp 111.5 °C; ½a ¼ ꢀ2:5 (c 0.61, CHCl3); 1H
D
NMR (400 MHz, CDCl3) d 7.40–7.23 (15H, m, Ph),
5.88 (1H, d, J = 5.1 Hz, NH), 5.15 (1H, d, J =
12.3 Hz, OCH2Ph), 5.02 (1H, d, J = 12.3 Hz, OCH2Ph),
4.94 (1H, m, C(20)H), 3.90–3.73 (4H, m, C(4)H2 and
C(5)H2), 2.94 (1H, d, J = 13.9 Hz, C(2)CH2Ph), 2.87
(1H, d, J = 13.9 Hz, C(2)CH2Ph), 2.11–1.97 (2H, m,
C(10)H2); 13C NMR (100 MHz, CDCl3) d 155.8, 140.1,
136.5, 136.0, 130.6, 128.5, 128.4, 128.1, 127.0, 126.6,
125.9, 110.5, 66.5, 65.6, 64.8, 52.0, 44.3, 44.1; IR (KBr
pellet) m 3333, 3062, 3033, 2959, 1688, 1537, 1497,
1451, 1258, 1027; HR-ESI-MS calculated for:
C26H28NO4 (M+H)+ 418.2018, found 418.2009.
4.9.6. (+)-(20S)-2-[-20-(N-benzyloxycarbonylamino)-20-
(3,4-dimethoxyphenyl)]-ethyl-2-methyl-1,3-dioxolane 13f.
Following the general procedure for protection of
ketones 12, b-aminoketone 12f (0.20 g) afforded, after
purification on silica gel (ethyl acetate/cyclohexane 1:1),
4.9.3.
(ꢀ)-(20S)-2-Ethyl-2-[20-(N-benzyloxycarbonyl-
ketoprotected adduct (+)-13f as a white solid (0.13 g,
25
amino)-20-phenyl]-ethyl-1,3-dioxolane 13c. Following
the general procedure for the protection of ketones 12,
b-aminoketone 12c (0.36 g) afforded, after purification
on silica gel (ethyl acetate/cyclohexane 1:1), ketopro-
60%): mp 88.0 °C; ½a ¼ þ0:9 (c 1.03, CHCl3);
1H NMR (400 MHz, CDDCl3) d 7.37–7.27 (5H, m, Ph),
6.87–6.76 (3H, m, ArH), 5.87 (1H, m, C(20)H), 5.11–
5.01 (2H, m, OCH2Ph), 4.79 (1H, br s, NH), 4.01–3.80
(10H, m, Ar(OCH3)2, C(4)H2 and C(5)H2), 2.08–1.99
(2H, m, C(10)H2), 1.32 (3H, s, C(1)Me); IR (KBr pellet)
m 3385, 3063, 3033, 2980, 2960, 2948, 2878, 1693, 1592,
1535, 1517, 1452, 1375, 1260, 1237, 1141, 1037; HR-
ESI-MS calculated for: C22H28NO6 (M+H)+ 402.1917,
found 402.1932.
tected adduct (ꢀ)-13c as a colourless oil (0.17 g, 42%):
25
½a ¼ ꢀ7:5 (c 1.32, CHCl3); 1H NMR (400 MHz,
D
CDCl3) d 7.34–7.16 (m, 10H, Ph), 5.88 (1H, br s, NH),
5.01 (1H, d, J = 12.0Hz, OC H2Ph), 4.93 (1H, d,
J = 12.0Hz, OC H2Ph), 4.74 (1H, m, C(20)H), 3.94–
3.72 (4H, m, C(4)H2 and C(5)H2), 1.93 (2H, m,
C(10)H2), 1.56 (2H, q, J = 7.5 Hz, C(2)CH2CH3), 0.82
(3H, t, J = 7.5 Hz, C(2)CH2CH3); 13C NMR
(100 MHz, CDCl3) d 155.8, 143.6, 136.7, 128.9, 128.5,
128.0, 127.6, 127.1, 125.9, 66.5, 65.3, 64.6, 52.3, 43.0,
30.3, 8.1; IR (neat) m 3428, 3032, 3016, 2976, 2886,
1717, 1507, 1455, 1261, 1236, 1074, 1043; HR-ESI-MS
calculated for: C21H25NO4Na (M+Na)+ 378.1681,
found 378.1696.
4.10. General procedure for hydrogenolysis of a
carbamate group
To a stirred solution of aminoketal 13 (1 equiv) in anhy-
drous methanol (5 mL/mmol of 13) was added 10% Pd/
C (40mg/mmol of 13) then ammonium formate
(5 equiv). The resulting suspension was heated at reflux
for 5 h. After cooling at room temperature, the catalyst
was removed by filtration on CeliteÒ. The residue ob-
tained after evaporation of the solvent was diluted with
dichloromethane. This organic phase was washed with a
saturated aqueous solution of sodium hydrogenocar-
4.9.4.
(ꢀ)-(20R)-2-Butyl-2-(20-N-benzyloxycarbonyl-
amino)-propyl-1,3-dioxolane 13d. Following the gen-
eral procedure for protection of ketones 12, b-amino-
ketone 12d (0.79 g) afforded, after purification on silica