70
A. S. Kende et al. / Tetrahedron 58 *2002) 61±74
Under the same conditions 31 was obtained in 68% isolated
yield. 31: mp 114±1158C 8heptane/ethyl acetate). IR 8®lm):
2931, 2857, 1762, 1694, 1666, 1612, 1513, 1463, 1392,
drops of a solution of 1-[84-bromobutoxy)methyl]-4-meth-
oxy-benzene 8568 mg, 2.08 mmol) in THF 82.0 mL) were
added. Once the iodine color disappeared, the remaining
bromide solution was added dropwise 85±10min), and the
reaction mixture was stirred for an additional 20±25 min.
The Grignard reagent was added dropwise to a stirred
suspension of CuBr´Me2S 85.0 mg, 0.024 mmol) and
HMPA 80.23 mL, 1.30 mmol) in THF 81.0 mL) at 2788C.
After 10min, a solution of 32 8200 mg, 0.52 mmol) and
TMSCl 80.13 mL, 1.04 mmol) in THF 89.0 mL) was added
dropwise at 2788C. The reaction mixture was stirred
vigorously for 30min then quenched with saturated
NH4Cl solution 810mL) and diluted with Et 2O. The layers
were separated, the aqueous layer was extracted with
EtOAc, and the combined organic layers were washed
with brine and dried 8Na2SO4). The solvents were evapo-
rated under reduced pressure, and the residue was
chromatographed 8hexanes/EtOAc 1:1 then 1:2) to obtain
223 mg 874%) of a 6.4:1 mixture of 35a/b. 35a: IR 8®lm):
2935, 2860, 1770, 1694, 1660, 1612, 1585, 1514, 1456,
1
1321, 1248, 1175, 1132, 1024, 974, 940, 839 cm21. H
NMR 8C6D6): 0.04 83H, s); 0.15 83H, s); 0.89 89H, s);
1.51 81H, td, J9.5, 11.9 Hz); 1.76 83H, s); 2.02 81H, dd,
J2.2, 15.8 Hz); 2.02±2.08 81H, m); 2.12±2.16 82H, m);
2.36 81H, dd, J2.8, 15.8 Hz); 3.27 83H, s); 3.32 83H, s);
4.21 81H, d, J15.6 Hz); 4.6081H, t, J2.5 Hz); 5.44 81H,
d, J15.6 Hz); 6.79 82H, d, J8.6 Hz); 7.34 82H, d, J
8.6 Hz) ppm. 13C NMR 8C6D6): 24.9, 24.6, 8.7, 18.1,
25.5 83C), 29.9, 30.0, 38.7, 44.7, 54.8, 58.4, 71.8, 91.4,
99.0, 106.3, 114.1 82C), 129.2 82C), 132.6, 149.4, 159.2,
170.7, 172.3, 174.8 ppm. APCI81): 500 8[MH]1, 100),
392 87). HRMS 8DCI/NH3). Calcd for C27H38NO6Si m/z
500.2468; found 500.2450. Elemental analysis. Calcd C,
64.90; H, 7.46; found C, 64.98; H, 7.67.
4.1.7. Installation of the double bond to yield 32 and 33.
The TBDMS enol ethers 82.4 g, 4.81 mmol of 30; 3.0g,
6.13 mmol of 31) were dissolved in dry DMSO 820mL/
mmol) and 10%Pd8OAc)2 was added. The reaction mixture
was stirred at 808C under oxygen atmosphere for 45 h 830)
and for 53 h 831). Additional amounts of Pd8OAc)2 were
added up to 0.85 equiv. The reaction mixture was cooled
to rt and diluted with EtOAc and saturated NaHCO3 solution
was added. The aqueous layer was extracted with EtOAc,
and the combined organic layers were washed with H2O,
brine and dried 8Na2SO4). Chromatography on silica gel
8hexanes/EtOAc 1:2 for 32 or EtOAc for 33) afforded
1.7 g 893%) of 32 and 2.1 g 889%) of 33. 32: mp 142±
1438C 8heptane/ethyl acetate). IR 8®lm): 2940, 1769,
1732, 1704, 1662, 1514, 1386, 1343, 1248, 1144,
1390, 1322, 1247, 1175, 1070, 1033, 873, 819, 753 cm21
.
1H NMR 8CDCl3): 0.85±0.95 81H, m); 0.99±1.06 82H, m);
1.20±1.40 83H, m); 1.75 83H, s); 1.97±2.09 83H, m); 2.36
81H, ddd, J2.6, 9.7, 17.1 Hz); 2.74 81H, t, J9.7 Hz); 2.76
81H, dd, J9.2, 19.7 Hz); 2.93±3.02 81H, m); 3.33 82H, dt,
J2.1, 6.2 Hz); 3.76 83H, s); 3.81 83H, s); 3.98 83H, s); 4.21
81H, d, J15.6 Hz); 4.38 81H, d, J11.6 Hz); 4.42 81H, d,
J11.6 Hz); 4.68 81H, d, J15.6 Hz); 6.83 82H, d, J
8.6 Hz); 6.89 82H, d, J8.6 Hz); 7.13 82H, d, J8.6 Hz);
7.25 82H, d, J8.6 Hz) ppm. 13C NMR 8CDCl3): 8.8, 23.2,
25.0, 29.1, 29.2, 29.8, 35.9, 40.2, 43.1, 55.2 82C), 59.7, 69.5,
72.5, 74.7, 90.9, 100.3, 113.7 82C), 113.8 82C), 128.5 82C),
129.3 82C), 130.1, 130.5, 158.8, 159.2, 167.8, 172.1, 176.8,
205.9 ppm. APCI81): 578 8[MH]1, 100), 458 845), 121
840). HRMS 8DCI/NH3). Calcd for C33H40NO8 m/z
578.2754; found 578.2741.
1070 cm21 1H NMR 8CDCl3): 1.95 83H, s); 2.03 81H,
.
ddd, J8.9, 12.1, 13.0Hz); 2.35 81H, dd, J8.9,
16.8 Hz); 2.44 81H, dd, J7.9, 13.0Hz); 2.64 81H, ddd,
J7.9, 12.1, 16.8 Hz); 3.78 83H, s); 3.87 83H, s); 4.10
81H, d, J15.6 Hz); 4.88 81H, d, J15.6 Hz); 6.33 81H, d,
J6.3 Hz); 6.84 82H, d, J8.6 Hz); 7.07 82H, d, J8.6 Hz);
7.21 81H, d, J6.3 Hz) ppm. 13C NMR 8CDCl3): 8.9, 29.4,
32.8, 44.4, 55.2, 59.3, 73.4, 89.5, 99.7, 114.082C), 128.4
82C), 129.8, 132.5, 158.9, 162.5, 168.1, 172.6, 176.0,
195.4 ppm. APCI 81): 384 8[MH]1, 100), 276 825), 121
855). HRMS 8DCI/NH3). Calcd for C21H22NO6 m/z
384.1447; found 384.1434. Elemental analysis. Calcd C,
65.79; H, 5.52. Found C, 65.97; H, 5.69. 33: mp 153±
1548C 8heptane/ethyl acetate/CH2Cl2). IR 8®lm): 2925,
1770, 1732, 1698, 1662, 1514, 1389, 1321, 1247, 1176,
Under the same conditions, from 1.4 g 83.68 mmol) of 33
were obtained 1.37 g 857%) of 36 and 674 mg 832%) of 37
8chromatography on silica gel 8hexanes/EtOAc 1:2 then
1
EtOAc)). 36: H NMR 8CDCl3): 0.17 89H, s); 0.69±0.75
81H, m); 0.99±1.05 81H, m); 1.17±1.31 84H, m); 1.87±
1.95 81H, m); 1.97 83H, s); 2.02±2.19 82H, m); 2.23±2.29
81H, m); 2.63±2.67 81H, m); 3.20±3.25 82H, m); 3.67 83H,
s); 3.73 83H, s); 4.04 83H, s); 4.12 81H, d, J15.8 Hz); 4.31
82H, s); 4.99 81H, d, J2.5 Hz); 5.02 81H, d, J15.8 Hz);
6.73 82H, d, J8.4 Hz); 6.81 82H, d, J8.6 Hz); 7.13 82H, d,
J8.6 Hz); 7.17 82H, d, J8.4 Hz) ppm. 13C NMR
8CDCl3): 20.3 83C), 8.6, 24.0, 24.5, 29.3 82C), 30.1, 44.2,
44.8, 54.9 82C), 59.1, 69.4, 72.1, 74.8, 93.3, 99.9, 111.3,
113.4 84C), 128.5 82C), 128.9 82C), 130.3, 131.3, 147.9,
158.3, 158.8, 169.9, 172.4, 175.8 ppm. APCI81): 650
8[MH]1, 100), 578 820). 37: mp 147±1488C 8heptane/
CH2Cl2). IR 8®lm): 2934, 2858, 1768, 1694, 1661, 1612,
1585, 1514, 1456, 1393, 1334, 1303, 1247, 1178, 1098,
1
1063 cm21. H NMR 8CDCl3): 2.08 83H, s); 2.11±2.19
81H, m); 2.31±2.54 83H, m); 3.64 81H, d, J15.9 Hz);
3.79 83H, s); 4.09 83H, s); 5.13 81H, d, J15.9 Hz); 6.26
81H, d, J6.1 Hz); 6.79 82H, d, J8.6 Hz); 7.02 81H, d, J
6.1 Hz); 7.05 82H, d, J8.6 Hz) ppm. 13C NMR 8CDCl3):
8.8, 27.7, 29.2, 44.1, 55.1, 59.5, 72.0, 85.9, 98.9, 113.8 82C),
129.082C), 129.7, 133.7, 158.7, 163.6, 169.2, 172.4, 174.5,
197.9 ppm. APCI 81): 384 8[MH]1, 100), 276 852), 121
845). HRMS 8DCI/NH3). Calcd for C21H22NO6 m/z
384.1447; found 384.1449. Elemental analysis. Calcd C,
65.79; H, 5.52. Found C, 64.12; H, 5.49.
1
1035, 1006, 930, 909, 820, 753, 735, 668 cm21. H NMR
8CDCl3): 0.60±0.69 81H, m); 0.73±0.80 81H, m); 0.88±0.98
81H, m); 1.10±1.19 82H, m); 1.20±1.29 81H, m); 1.92±2.01
82H, m); 2.05 83H, s); 2.20 81H, ddd, J3.2, 7.7, 13.0Hz);
2.35±2.5082H, m); 2.76±2.87 82H, m); 3.20±3.27 82H, m);
3.74 83H, s); 3.82 83H, s); 4.14 83H, s); 4.34 81H, d, J
15.4 Hz); 4.36 81H, d, J11.6 Hz); 4.38 81H, d, J
11.6 Hz); 5.04 81H, d, J15.4); 6.79 82H, d, J8.6 Hz);
4.1.8. 1,4-Addition to 32 and 33. To a stirred mixture of
magnesium turnings 8101 mg, 4.16 mmol) and a catalytic
amount of I2 in dry THF 82.0mL) under re¯ux, some