3576
J. G. Marrero, L. M. Harwood / Tetrahedron Letters 50 (2009) 3574–3576
diethyl [cyano(morpholino)methyl]phosphonate (814.2 mg, 3.1 equiv) in THF
(3 mL) was added. The mixture was stirred for a further 1 h, then 6-oxohexyl 2-
181 (24), 169 (23), 151 (55), 135 (76), 119 (35), 69 (100), 57 (16). HRMS:
20H26N2O4, calcd: 358.1893, found: 358.1904.
C
methyl-5-vinyl-3-furoate (243.6 mg, 1.0 mmol) in THF (3 mL) was added
dropwise at ꢀ78 °C. After 1 h at this temperature, the reaction mixture was
quenched with 5% HCl (2 mL). The aqueous layer was extracted with ether
(3 ꢁ 25 mL), the combined organic layers were washed with brine (10 mL),
dried (MgSO4), filtered and the solvent removed under reduced pressure.
Purification by flash column chromatography on silica gel, eluting with light
petroleum–diethyl ether (2:1), furnished 12 as an inseparable 3:1 mixture of
alkene geometric isomers (249.1 mg, 71%). 1H NMR (d, ppm, 250 MHz, CDCl3):
1.38–1.44 (5H, m), 1.66–1.68 (2H, m), 2.28–2.30 (2H, m), 2.53 (3H, s), 2.64–
2.66 (2H, m), 2.80–2.85 (3H, m), 3.65–3.72 (4H, m), 4.14–4.20 (2H, m), 5.13
(1H, d, J 11.3), 5.22 (0.75H, t, J 7.9), 5.60 (1H, d, J 17.5), 5.91 (0.25H, t, J 7.9),
6.35–6.42 (1H, m), 6.42 (1H, s). 13C NMR (d, ppm, 100.4 MHz, CDCl3): 14.2
(CH3), 25.7 (CH2), 26.0 (CH2), 27.2 (CH2), 28.3 (CH2), 28.8 (CH2), 29.7 (CH2), 49.6
(CH2), 51.7 (CH2), 64.2 (CH2), 66.5 (CH2), 66.9 (CH2), 108.8 (CH), 113.1 (CH2),
114.8 (4 °C), 115.2 (C„N), 121.8 (CH), 124.7 (CH), 126.1 (4 °C), 141.5 (CH),
11. High pressure reaction procedure: A solution of 12 (201.3 mg, 0.6 mmol) in
dichloromethane (8 mL) was subjected to high pressure (19 kbar) for 24 h at
25 °C. On depressurisation, the solution was filtered through a plug of cotton
wool, and the solvent removed under reduced pressure to afford the crude
product. Purification by flash column chromatography on silica gel, eluting
with light petroleum–diethyl ether (2:1) furnished the desired compound 13
as a 7:2 mixture of C-4 epimers (151 mg, 75%). 1H NMR (d, ppm, 250 MHz,
CDCl3): 1.43 (3H, s), 1.70 (2H, q, J 7.0 Hz), 2.23–2.33 (3H, m), 2.45 (3H, s), 2.71
(2H, t, J 4.6 Hz), 2.88–2.91 (4H, m), 3.75 (4H, t, J 4.5 Hz), 4.18 (2H, m), 5.11 (1H,
d, J 3.4 Hz), 5.26 (0.7H, m), 5.95 (0.3H, m). 13C NMR (d, ppm, 100.4 MHz, CDCl3):
14.3 (CH3), 25.8 (CH2), 28.4 (CH2), 28.9 (CH2), 30.7 (CH2), 33.8 (CH), 45.5 (CH),
49.5 (CH2), 51.7 (CH2), 64.1 (CH2), 66.3 (CH2), 64.2 (CH2), 66.7 (CH2), 98.4 (CH),
106.3 (4 °C), 107.4 (4 °C), 114.9 (C„N), 121.9 (4 °C), 126.1 (CH), 153.6 (4 °C),
165.5 (4 °C), 167.2 (C@O, ester). I. R. m
max (film, cmꢀ1): 2820, 2250, 1735, 1644,
1203. MS (m/z, %, E. I.): 358 ([M]+, 44), 343 (8), 252 (23), 223 (42), 175 (16), 159
(9), 145 (55), 130 (87), 102 (19), 69 (100), 57 (16). HRMS: C20H26N2O4, calcd:
358.1893, found: 358.1945.
151.2 (4 °C), 159.1 (4 °C), 164.2 (C@O, ester). I. R.
m
max (film, cmꢀ1): 2835, 2227,
1725, 1624, 1153. MS (m/z, %, E. I.): 358 ([M]+, 32), 281 (11), 231 (13), 223 (62),