Ahmed et al.
followed by addition of dienoate. The reaction was stirred vigor-
ously at 0 °C for 2-18 h. Ethyl acetate was added to the reaction
mixture followed by quenching with solid sodium sulfite. The layers
were separated, and the aqueous layer was extracted with EtOAc.
The combined organic layers were washed with brine and then dried
over Na2SO4. After concentration the crude mixture was purified
by silica gel column chromatography.
15.6 Hz, 1H), 6.11 (d, J ) 15.6 Hz, 1H), 4.60 (d, J ) 3.0 Hz, 1H),
4.19 (q, J ) 7.2 Hz, 2H), 2.70 (s, 1H), 2.47 (s, 1H), 1.28 (t, J )
7.2 Hz, 3H), 1.17 (s, 3H); 13C NMR (CDCl3, 150 MHz) δ 166.5
151.8, 138.9, 128.2, 128.1 (2C), 127.5 (2C), 120.5, 79.2, 75.5, 60.4,
22.9, 14.1; HRMS (ESI) calcd for [C14H18O4 + Na]+ 273.1097,
found 273.1091
(+)-(E,4R,5S)-Ethyl 4,5-dihydroxy-4-methylhex-2-enoate (17).
After purification by flash column chromatography (30% EtOAc/
hexanes) the reaction yielded 153 mg (64%) of diol as a clear,
colorless oil. Rf ) 0.10 (4:1 hexanes/EtOAc), [R]24D +2.5 (c 1.00,
CH2Cl2); IR (neat, cm-1) 3434 (br), 2980, 2936, 1699, 1655, 1449,
1368, 1303, 1276, 1181, 1090, 1033, 985, 920, 887, 729; 1H NMR
(CDCl3, 600 MHz) δ 6.97 (d, J ) 15.6 Hz, 1H), 6.11 (d, J ) 15.6
Hz, 1H), 4.19 (q, J ) 7.2 Hz, 2H), 3.71 (q, J ) 6.6 Hz, 1H), 2.64
(brs, 1H), 2.28 (brs, 1H), 1.31 (s, 3H), 1.28 (t, J ) 7.2 Hz, 3H),
1.17 (dd, J ) 6.6, 1.2 Hz, 3H); 13C NMR (CDCl3, 150 MHz) δ
166.7, 150.0, 121.2, 75.6, 74.0, 60.7, 24.6, 18.2, 14.4.
General Procedure for Carbonate Formation. To diol in
CH2Cl2 (0.4 M) in an ice bath was added pyridine (5 equiv).
Triphosgene (1.1 equiv) in CH2Cl2 (0.4 M, total reaction concen-
tration equals 0.2 M) was added via syringe, and the reaction was
allowed to stir for 5 min until determined complete by TLC (UV,
PMA stain). The reaction was diluted with diethyl ether and was
placed in a separatory funnel. The crude mixture, including salts,
was washed vigorously with a saturated aqueous CuSO4 solution
until all salts dissolved. The layers were then separated, and the
organic layer was washed with brine. After separation the organic
layer was dried over Na2SO4 and concentrated. The crude mixture
was then purified by flash column chromatography.
(+)-(E,4S,5S)-Ethyl 7-(tert-Butyldimethylsilyloxy)-4,5-dihy-
droxy-4-methylhept-2-enoate (7a). After flash column chroma-
tography (30% EtOAc/hexanes) the reaction yielded 380 mg (68%)
of diol as a clear, colorless oil. Rf ) 0.10 (4:1 hexanes/EtOAc),
[R]24D +5.2 (c 0.61, CH2Cl2); IR (neat, cm-1) 3459(br), 2932, 2859,
1713, 1658, 1469, 1369, 1257, 1183, 1089, 987, 941, 836, 778,
1
728; H NMR (CDCl3, 600 MHz) δ 6.99 (d, J ) 15.6 Hz, 1H),
6.11 (d, J ) 15.6 Hz, 1H), 4.17 (q, J ) 7.2 Hz, 2H), 3.90 (m, 2H),
3.74 (dd, J ) 6, 6 Hz, 1H), 1.99 (brs, 2H), 1.71 (m, 2H), 1.27 (t,
J ) 7.2 Hz, 3H), 1.25 (s, 3H), 0.88 (s, 9H), 0.07 (s, 6H); 13C NMR
(CDCl3, 150 MHz) δ 166.6, 152.3, 120.2, 77.2, 74.6, 62.5, 60.3,
32.2, 25.7 (3C), 22.8, 18.0, 14.1, -5.6 (2C); HRMS (ESI) calcd
for [C16H32O5Si + Na]+ 355.1911, found 355.1909.
(+)-(E,4S,5S)-Ethyl 7-(Benzyloxy)-4,5-dihydroxy-4-methyl-
hept-2-enoate (7b). After purification by flash column chroma-
tography (50% EtOAc/hexanes) the diol was obtained in 71% yield
as a clear, colorless oil. Rf ) 0.11 (4:1 hexanes/EtOAc), [R]24
D
+5.2 (c 2.0, CH2Cl2); IR (neat, cm-1) 3461(br), 2931, 2860, 1715,
1
1453, 1367, 1282, 1186, 1095, 1031, 987, 698; H NMR (CDCl3,
600 MHz) δ 7.35 (m, 3H), 7.30 (m, 2H), 6.99 (d, J ) 15.6 Hz,
1H), 6.11 (d, J ) 15.6 Hz, 1H), 4.52 (s, 2H), 4.18 (q, J ) 7.2 Hz,
2H), 3.75 (m, 2H), 3.68 (m, 1H), 3.51 (s, 1H), 2.71 (s, 1H), 1.81
(m, 2H), 1.28 (t, J ) 7.2 Hz, 3H), 1.27 (s, 3H); 13C NMR (CDCl3,
150 MHz) δ 166.5, 152.0, 138.1, 128.5 (2C), 127.9, 127.7 (2C),
120.3, 76.7, 74.6, 73.5, 69.2, 60.4, 30.2, 22.8, 14.2; HRMS (ESI)
calcd for [C17H24O5 + Na]+ 331.1515, found 331.1516.
(+)-(E)-Ethyl 3-((4S,5S)-5-Isobutyl-4-methyl-2-oxo-1,3-diox-
olan-4-yl)acrylate (13a). The crude mixture was purified by flash
column chromatography (20% EtOAc/hexanes) to yield carbonate
in 90% yield as a clear, colorless oil. Rf ) 0.26 (4:1 hexanes/
EtOAc), [R]24D +35.6 (c 1.0, CH2Cl2); IR (neat, cm-1) 2961, 1799,
1719, 1663, 1468, 1385, 1367, 1309,1280, 1232, 1177, 1088, 1063,
(-)-(E,4S,5S)-Ethyl 4,5-Dihydroxy-4,7-dimethyloct-2-enoate
(11a). After purification by flash column chromatography (50%
EtOAc/hexanes) the reaction yielded 44 mg (75%) of diol as a clear
oil with no detectable regioisomer. Rf ) 0.15 (4:1 hexanes/EtOAc),
1
1013, 982, 870, 774; H NMR (CDCl3, 600 MHz) δ 6.85 (d, J )
15.6 Hz, 1H), 6.16 (d, J ) 15.6 Hz, 1H), 4.41 (dd, J ) 10.8, 2.4
Hz, 1H), 4.22 (q, J ) 7.2 Hz, 2H), 1.84 (m, 1H), 1.71 (m, 1H),
1.46 (s, 3H), 1.32 (m, 1H), 1.30 (t, J ) 7.2 Hz, 3H), 0.99 (d, J )
6.6 Hz, 3H), 0.95 (d, J ) 7.2 Hz, 3H); 13C NMR (CDCl3, 150
MHz) δ 165.3, 153.2, 144.0, 122.3, 84.15, 82.0, 61.0, 37.4, 25.1,
23.1, 21.5, 19.2, 14.1; HRMS (ESI) calcd for [C13H20O5 + Na]+
279.1202, found 279.1204.
[R]24 -21.7 (c 1.0, CH2Cl2); IR (neat, cm-1) 3460, 2957, 2870,
D
1701, 1656, 1466, 1368, 1307, 1282, 1189, 1034, 988, 869, 766,
1
743, 652; H NMR (CDCl3, 600 MHz) δ 6.95 (d, J ) 15.6 Hz,
1H), 6.10 (d, J ) 15.6 Hz, 1H), 4.19 (q, J ) 7.2 Hz, 2H), 3.56
(ddd, J ) 10.8, 4.2, 2.4 Hz, 1H), 2.53 (brs, 1H), 2.31 (brs, 1H),
1.80 (m, 1H), 1.38 (ddd, J ) 13.8, 10.8, 3.6 Hz, 1H), 1.28 (t, J )
7.2 Hz, 3H),1.26 (s, 3H), 1.20 (ddd, J ) 13.8, 10.2, 4.2 Hz, 1H),
0.94 (d, J ) 6.6 Hz, 3H), 0.88 (d, J ) 6.6 Hz, 3H); 13C NMR
(CDCl3, 150 MHz) δ 166.6, 151.9, 120.6, 75.4, 74.7, 60.5, 39.7,
24.6, 23.8, 21.8, 21.2, 14.1; HRMS (ESI) calcd for [C12H22O4 +
Na]+ 253.1410, found 253.1402.
(+)-(E)-Ethyl 3-((4S,5S)-5-Isopropyl-4-methyl-2-oxo-1,3-di-
oxolan-4-yl)acrylate (13b). The crude mixture was purified by flash
column chromatography (20% EtOAc/hexanes) to yield carbonate
in 84% yield as a clear, colorless oil. Rf ) 0.22 (4:1 hexanes/
EtOAc), [R]24D +18.3 (c 1.0, CH2Cl2); IR (neat, cm-1) 2973, 1801,
1720, 1663, 1472, 1368, 1281, 1245, 1175, 1109, 1062, 1027, 982,
(-)-(E,4S,5S)-Ethyl 4,5-Dihydroxy-4,6-dimethylhept-2-enoate
(11b). After purification by silica gel column chromatography (30%
EtOAc/hexanes) the reaction yielded 72 mg (60%) of diols as a
1
839, 774; H NMR (CDCl3, 600 MHz) δ 6.84 (d, J ) 15.6 Hz,
1H), 6.20 (d, J ) 15.6 Hz, 1H), 4.23 (q, J ) 7.2 Hz, 2H), 3.98 (d,
J ) 9.6 Hz, 1H), 2.04 (m, 1H), 1.54 (s, 3H), 1.30 (t, J ) 7.2 Hz,
3H), 1.11 (d, J ) 6.6 Hz, 3H), 0.95 (d, J ) 6.6 Hz, 3H); 13C NMR
(CDCl3, 150 MHz) δ 165.6, 153.1, 144.5, 123.0, 89.1, 84.5, 61.2,
28.2, 19.8, 19.1, 18.7, 14.3; HRMS (ESI) calcd for [C12H18O5 +
Na]+ 265.1046, found 265.1050.
16:1 mixture of regioisomers. Rf ) 0.11 (4:1 hexanes/EtOAc), [R]24
D
-3.0 (c 0.5, CH2Cl2); IR (neat, cm-1) 3448, 2962, 2874, 1698,
1655, 1467, 1368, 1303, 1279, 1179, 1096, 1031, 984, 869, 725,
1
679; H NMR (CDCl3, 600 MHz) δ 6.89 (d, J ) 15.6 Hz, 1H),
5.99 (d, J ) 15.6 Hz, 1H), 4.10 (q, J ) 7.2 Hz, 2H), 3.27 (dd, J )
4.8, 3.6 Hz, 1H), 2.32 (s, 1H), 1.95 (d, J ) 4.8 Hz, 1H), 1.86 (m,
1H), 1.22 (s, 3H), 1.19 (t, J ) 7.2 Hz, 3H), 0.90 (d, J ) 6.6 Hz,
3H), 0.89 (d, J ) 6.6 Hz, 3H); 13C NMR (CDCl3, 150 MHz) δ
166.8, 153.4, 120.2, 80.1, 75.6, 60.7, 29.0, 23.1, 22.0, 16.6, 14.4;
HRMS (ESI) calcd for [C11H20O4 + Na]+ 239.1253, found
239.1249.
(-)-(E)-Ethyl 3-((4S,5S)-4-Methyl-2-oxo-5-phenyl-1,3-diox-
olan-4-yl)acrylate (13c). The crude mixture was purified by flash
column chromatography (20% EtOAc/hexanes) to yield carbonate
in 91% yield as a clear, colorless oil. Rf ) 0.21 (4:1 hexanes/
EtOAc), [R]24D -24.9 (c 1.3, CH2Cl2); IR (neat, cm-1) 2984, 1802,
1718, 1663, 1456, 1367, 1308, 1288, 1245, 1180, 1088, 1069, 1044,
1028, 979, 771, 700; 1H NMR (CDCl3, 600 MHz) δ 7.43 (m, 3H),
7.28 (m, 2H), 7.01 (d, J ) 15.6 Hz, 1H), 6.20 (d, J ) 15.6 Hz,
1H), 5.47 (s, 1H), 4.26 (qd, J ) 7.2, 1.2 Hz, 2H), 1.32 (t, J ) 7.2
Hz, 3H), 1.12 (s, 3H); 13C NMR (CDCl3, 150 MHz) δ 165.3, 153.0,
144.5, 132.2, 129.5, 128.9 (2C), 125.5 (2C), 122.6, 85.2, 84.4, 61.1,
20.9, 14.1; HRMS (ESI) calcd for [C15H16O5 + Na]+ 299.0889,
found 299.0897.
(+)-(S,E)-Ethyl 4-Hydroxy-4-((S)-hydroxy(phenyl)methyl)-
pent-2-enoate (11c). After purification by flash column chroma-
tography (50% EtOAc/hexanes) the reaction yielded 490 mg (60%)
of diol as a clear, yellow oil. Rf ) 0.10 (4:1 hexanes/EtOAc), [R]24
D
+15.7 (c 1.2, CH2Cl2); IR (neat, cm-1) 3436, 2981, 1699, 1656,
1453, 1368, 1304, 1278, 1182, 1094, 1026, 985, 910, 868, 721,
1
700; H NMR (CDCl3, 600 MHz) δ 7.33 (m, 5H), 7.01 (d, J )
7744 J. Org. Chem., Vol. 71, No. 20, 2006