7.44 (2H, t, J = 7.2 Hz, Ph–H), 7.31 (1H, dd, J1 = 7.8 Hz, J2 =
1.2 Hz, Ar–H), 7.09–7.04 (1H, m, Ar–H), 6.97 (1H, s, CH2),
6.83–6.81 (1H, m, Ar–H), 6.63–6.60 (1H, m, Ar–H), 6.37 (1H, s,
CH2), 5.71 (1H, s, Ar–CH), 3.87 (3H, s, Ar–OCH3), 2.45 (1H,
qu, J = 6.8 Hz, -CH(CH3)2), 2.27 (3H, s, COCH3), 1.12 (3H, d,
J = 6.8 Hz, -CH(CH3)2), 0.84 (3H, d, J = 6.8 Hz, -CH(CH3)2); 1H
NMR (400 MHz, CDCl3, TMS) for anti-3e: d 7.57–7.55 (2H, m),
7.34–7.24 (5H, m), 6.88–6.73 (2H, m), 6.60 (1H, s), 6.29 (1H, s),
6.01 (1H, s), 3.84 (3H, s), 2.79 (1H, qu, J = 6.8 Hz), 2.21 (3H,
s), 1.22 (3H, d, J = 6.8 Hz), 1.13 (3H, d, J = 6.8 Hz); 13C NMR
(100 MHz, CDCl3) for syn-3e: d 198.5, 177.7, 159.9, 157.1, 147.4,
132.4, 130.9, 128.6, 128.4, 128.3, 127.7, 125.8, 125.3, 119.4, 111.4,
80.0, 56.0, 38.1, 32.5, 26.0, 17.4, 15.8; 13C NMR (100 MHz, CDCl3)
for anti-3e: d 197.7, 168.5, 158.1, 146.1, 137.8, 130.5, 129.9, 128.7,
128.3, 128.1, 127.3, 126.7, 126.1, 119.6, 111.3, 69.9, 56.1, 43.3, 28.0,
27.7, 25.7, 19.0, 18.8; MS (EI(syn-3e)) m/z (%) 391 (0.51) [M+],
190 (6.62), 189 (47.94), 147 (20.16), 131 (6.13), 115 (4.41), 105
(31.61), 86 (61.28), 84 (100.00), 77 (23.16), 43 (89.95); HRMS (EI)
Calcd for C24H25NO4 [M+] requires 391.1784, Found 391.1785; MS
(ESI(anti-3e)) m/z 392 (M+ + H); HRMS (ESI) for C24H26NO4
(M+ + H): 392.1861, Found: 392.1856. The ee of the syn-
diastereomer was determined to be 95% [determined by HPLC,
Chiralpak AD-H, n-hexane/isopropanol = 90 : 10, 0.7 mL min-1,
l = 230 nm, t (major) = 7.02 min, t (minor) = 8.57 min];
The ee of the anti-diastereomer was determined to be 94%
[determined by HPLC, Chiralpak IC-H, n-hexane/isopropanol =
95 : 5, 0.3 mL min-1, l = 230 nm, t (major) = 31.09 min, t (minor) =
31.33 min].
NMR spectroscopic analysis of the crude product (d major:
2.50 ppm, d minor: 2.78 ppm). The mixture was purified by
column chromatography using silica gel to give a mixture of
diastereoisomers along with a trace amount of impurity (37 mg,
86% overall yield in a diastereomeric ratio = 16 : 1); a white solid.
m.p. for syn-3g = 122–123 ◦C; [a]D20 (syn-3g) = -57.3 (c 0.8, CHCl3).
IR (CH2Cl2): n 2978, 2881, 1813, 1673, 1650, 1617, 1493, 1451,
1323 1292, 1251, 1198, 1128, 1110, 1043, 1018, 986, 969, 911, 881,
1
821, 781 cm-1; H NMR (400 MHz, CDCl3, TMS) for syn-3g: d
7.86 (2H, d, J = 7.2 Hz, Ph–H), 7.55 (1H, t, J = 7.8 Hz, Ph–H),
7.44 (2H, t, J = 7.2 Hz, Ph–H), 7.33–7.38 (5H, m, Ar–H and
CH2), 6.54 (1H, s, CH2), 5.00 (1H, s, Ar–CH), 2.50 (1H, qu,
J = 6.8 Hz, -CH(CH3)2), 2.33 (3H, s, COCH3), 1.11 (3H, d, J =
6.8 Hz, -CH(CH3)2), 0.82 (3H, d, J = 6.8 Hz, -CH(CH3)2); 13C
NMR (100 MHz, CDCl3) for syn-3g: d 198.0, 177.8, 160.4, 145.6,
140.7, 132.8, 130.6, 129.5 (q, JC–F = 32.0 Hz), 129.2, 128.7, 127.7,
125.3, 124.8 (q, JC–F = 3.7 Hz), 123.9 (q, JC–F = 207.7 Hz), 79.7,
46.6, 32.3, 25.5, 17.4, 15.3; 19F NMR (376 MHz, CDCl3, CFCl3):
d (syn-3g) -62.7; MS (EI(syn-3g)) m/z (%) 429 (1.67) [M+], 202
(24.30), 174 (5.44), 165 (0.60), 106 (8.18), 105 (100.00), 84 (9.37),
77 (23.72), 43 (26.76); HRMS (EI) Calcd for C24H22F3NO3 [M+]
requires 429.1552, Found 429.1557; the ee of the syn-diastereomer
was determined to be 96% [determined by HPLC, Chiralpak AD-
H, n-hexane/isopropanol = 95 : 5, 0.7 mL min-1, l = 230 nm, t
(major) = 7.02 min, t (minor) = 8.57 min].
(S)-4-Isopropyl-4-((R)-1-(3-methoxyphenyl)-2-methylene-3-
oxobutyl)-2-phenyloxazol-5(4H)-one 3h. Following the general
procedure, the syn/anti ratio (12 : 1) was determined by 1H
NMR spectroscopic analysis of the crude product (d major:
2.47 ppm, d minor: 2.77 ppm). The mixture was purified by
column chromatography using silica gel to give a mixture of
diastereoisomers along with a trace amount of impurity (36 mg,
92% overall yield in a diastereomeric ratio = 12 : 1); a white solid.
m.p. for syn-3h = 117–119 ◦C; [a]D20 (syn-3h) = -49.8 (c 0.7, CHCl3).
IR (CH2Cl2): n 2974, 1818, 1680, 1651, 1597, 1491, 1467, 1451,
1294, 1259, 1244, 1199, 1154, 1111, 1045, 1021, 969, 902, 864,
(S)-4-((R)-1-(3-Bromophenyl)-2-methylene-3-oxobutyl)-4-iso-
propyl-2-phenyloxazol-5(4H)one 3f. Following the general pro-
1
cedure, the syn/anti ratio (15 : 1) was determined by H NMR
spectroscopic analysis of the crude product (d major: 2.47 ppm,
d minor: 2.80 ppm). The mixture was purified by column chro-
matography using silica gel to give a mixture of diastereoisomers
along with a trace amount of impurity (40 mg, 91% overall yield
in a diastereomeric ratio = 15 : 1); a white solid. m.p. for syn-3f =
154–156 ◦C; [a]D20 (syn-3f) = -71.8 (c 0.8, CHCl3). IR (CH2Cl2): n
2974, 2954, 1811, 1673, 1655, 1470, 1288, 1196, 1159, 1111, 1041,
1
794, 779, 729 cm-1; H NMR (300 MHz, CDCl3, TMS) for syn-
3h: d 7.87 (2H, d, J = 7.2 Hz, Ph–H), 7.53 (1H, t, J = 7.5 Hz,
Ph–H), 7.43 (2H, t, J = 7.2 Hz, Ph–H), 7.26 (1H, s, CH2),
7.00 (1H, t, J = 7.8 Hz, Ar–H), 6.82 (1H, d, J = 6.8 Hz, Ar–
H), 6.78–6.76 (1H, m), 6.61 (1H, dd, J1 = 10.8 Hz, J2 = 3.2 Hz,
Ar–H), 6.49 (1H, s, CH2), 4.92 (1H, s, Ar–CH), 3.57 (3H, s,
Ar–OCH3), 2.47 (1H, qu, J = 7.2 Hz, -CH(CH3)2), 2.32 (3H, s,
COCH3), 1.12 (3H, d, J = 7.2 Hz, -CH(CH3)2), 0.84 (3H, d, J =
7.2 Hz, -CH(CH3)2); 13C NMR (75 MHz, CDCl3) for syn-3h: d
198.2, 178.0, 160.1, 158.9, 146.1, 137.9, 132.5, 128.7, 128.6, 127.7,
125.6, 122.7, 115.3, 113.5, 80.0, 55.0, 46.9, 32.3, 25.7, 17.6, 15.4;
MS (EI(syn-3h)) m/z (%) 391 (4.95) [M+], 203 (4.09), 189 (77.39),
147 (45.34), 132 (6.29), 115 (8.73), 105 (100.00), 77 (52.88), 51
(5.77), 43 (84.84); HRMS (EI) Calcd for C24H25NO4 [M+] requires
391.1784, Found 391.1788; The ee of the syn-diastereomer was
determined to be >99% [determined by HPLC, Chiralpak AD-
H, n-hexane/isopropanol = 90 : 10, 0.7 mL min-1, l = 230 nm, t
(major) = 7.21 min, t (minor) = 17.78 min].
1
1019, 978, 916, 888, 876, 800, 731 cm-1; H NMR (400 MHz,
CDCl3, TMS) for syn-3f: d 7.87 (2H, d, J = 6.8 Hz, Ph–H), 7.55
(1H, t, J = 7.6 Hz, Ph–H), 7.45 (2H, t, J = 7.2 Hz, Ph–H), 7.35
(1H, s, Ar–H), 7.28 (1H, s, CH2), 7.19 (2H, dd, J1 = 8.0 Hz, J1 =
2.0 Hz, Ar–H), 6.97 (1H, t, J = 8.0 Hz, Ar–H), 6.52 (1H, s, CH2),
4.89 (1H, s, Ar–CH), 2.47 (1H, qu, J = 6.8 Hz, -CH(CH3)2), 2.34
(3H, s, COCH3), 1.10 (3H, d, J = 6.8 Hz, -CH(CH3)2), 0.82 (3H,
d, J = 6.8 Hz, -CH(CH3)2); 13C NMR (CDCl3, 100 MHz) for syn-
3f: d 198.0, 177.8, 160.4, 145.6, 138.8, 133.0, 132.7, 130.5, 129.5,
129.1, 129.0, 128.7, 127.8, 125.3, 121.6, 79.7, 46.6, 32.2, 25.6, 17.5,
15.3; MS (EI(syn-3f)) m/z (%) 439 (2.18) [M+], 237 (5.17), 202
(20.39), 174 (5.64), 158 (8.15), 115 (6.41), 105 (100.00), 84 (11.45),
77 (25.88), 43 (39.26); HRMS (EI) Calcd for C23H22BrNO3 [M+]
requires 439.0783, Found 439.0790; The ee of the syn-diastereomer
was determined to be 97% [determined by HPLC, Chiralpak IC-
H, n-hexane/isopropanol = 99 : 1, 0.7 mL min-1, l = 230 nm, t
(major) = 15.63 min, t (minor) = 8.57 min].
(S)-4-Isopropyl-4-((R)-2-methylene-3-oxo-1-(3-(trifluorophe-
nyl))butyl)-2-phenyloxazol-5(4H)-one 3i. Following the general
procedure, the syn/anti ratio (16 : 1) was determined by 1H
NMR spectroscopic analysis of the crude product (d major:
(S)-4-Isopropyl-4-((R)-2-methylene-3-oxo-1-(4-(trifluorophe-
nyl))butyl)-2-phenyloxazol-5(4H)-one 3g. Following the general
procedure, the syn/anti ratio (16 : 1) was determined by 1H
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 3349–3358 | 3355
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