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M. Nahmany, A. Melman / Tetrahedron 61 (2005) 7481–7488
the pure title compounds 10a as pale yellow oil (0.0567 g,
0.128 mmol, 64%) and the more polar 11a as pale yellow oil
(0.0331 g, 0.070 mmol, 35%). Compound 10a: [a]D23
C11.84 (c 0.55, CHCl3). IR (film): 3350 (br), 3002, 2935,
Bn), 138.4 (C, Bn), 139.9 (C), 178.9 (C]O). HRMS calcd
for C22H34NaO5 (MNaC) 401.2304, found 401.2313.
4.1.6. (K)-(2S,6E)-8-Benzyloxy-1,2-dihydroxy-2,6-
dimethyl-oct-6-en-3-one (12). To a solution of oxalyl
chloride (1.20 mL, 13.9 mmol) in anh. dichloromethane
(30 mL) at K78 8C under inert atmosphere (N2) was added
dropwise over period of 5 min a solution of DMSO
(2.16 mL, 30.4 mmol) in anh. dichloromethane (6 mL).
The reaction mixture was stirred for 10 min and a solution
of diol 10d (4.77 g, 12.60 mmol) in anh. dichloromethane
(15 mL) was added dropwise over period of 5 min. The
reaction mixture was stirred for 30 min and neat triethyl-
amine (8.8 mL, 64.0 mmol) was added dropwise over
period of 5 min. The reaction mixture was left to rt and
quenched by a 1% HCl solution (40 mL) after TLC analysis
showed total disappearance of diol 10d. The reaction
mixture was stirred for additional 10 min and the
dimethylsulfide by-product was distilled off (38 8C). The
residue was extracted with dichloromethane (2!50 mL),
washed with water (2!25 mL) and saturated NaHCO3 (2!
25 mL), dried (Na2SO4) and evaporated to give (C)-(2R)-
(6E)-2,2-Dimethyl-propionic acid 8-benzyloxy-2-hydroxy-
2,6-dimethyl-3-oxo-oct-6-enyl ester as pale yellow oil
(4.41 g, 11.72 mmol, 93%). [a]2D2 C6.14 (c 1.52, CHCl3).
IR (film): 3420 (br), 2937, 2858, 1721, 1651, 1454, 1368,
1283, 1151, 1063, 753 cmK1.1H NMR (300 MHz): 1.15 (s,
9H); 1.36 (s, 3H); 1.65 (s, 3H); 2.21–2.46 (m, 2H); 2.69 (t,
JZ8 Hz, 2H); 3.91 (s, 1H, ex); 4.02 (d, JZ7 Hz, 2H); 4.50
(s, 2H); 5.42 (t, JZ7 Hz, 1H); 7.27–7.37 (m, 5H, Ar). 13C
NMR (75 MHz): 16.4 (CH3), 20.5 (CH3), 27.2 (3!CH3,
t-Bu), 28.8 (CH2), 36.6 (CH2), 38.9 (C), 66.4 (CH2), 68.4
(CH2), 72.1 (CH2), 79.9 (C), 121.6 (C]CH), 127.5 (CH,
Bn), 127.7 (2!CH, Bn), 128.3 (2!CH, Bn), 138.4 (C, Bn),
138.5 (C]CH), 178.0 (C]O, ester) 210.9 (C]O, ketone).
To a solution of the resultant (C)-(2S,6E)-2,2-Dimethyl-
propionic acid 8-benzyloxy-2-hydroxy-2,6-dimethyl-3-oxo-
oct-6-enyl ester (2.65 g, 7.04 mmol) in methanol (25 mL) at
rt was added a solution of NaOH (7.04 mL of 1 N) in
methanol. The reaction mixture was stirred for 12 h. at rt,
neutralized to pH 6 by a few drops of 1% HCl solution,
concentrated to ca.10 mL, dissolved in ethyl acetate
(50 mL), washed with water (2!50 mL), dried (Na2SO4)
and evaporated to give the title product as pale yellow oil
(2.00 g, 6.83 mmol, 97%). [a]2D0 K0.82 (c 0.89, CHCl3). IR
(film): 3450 (br), 2923, 2859, 1711, 1452, 1370, 1060,
751 cmK1. 1H NMR (300 MHz): 1.27 (s, 3H); 1.66 (s, 3H);
2.35 (t, JZ8 Hz, 2H); 2.72 (t, JZ8 Hz, 2H); 3.62 (d, JZ
12 Hz, 1H); 3.85 (d, JZ12 Hz, 1H); 4.01 (d, JZ7 Hz, 2H);
4.50 (s, 2H); 5.42 (t, JZ7 Hz, 1H); 7.27–7.37 (m, 5H, Ar).
13C NMR (75 MHz): 16.7 (CH3), 21.3 (CH3), 32.6 (CH2),
34.3 (CH2), 66.4 (CH2), 67.8 (CH2), 72.2 (CH2), 79.6 (C),
121.4 (C]CH), 127.6 (CH, Bn), 127.8 (2!CH, Bn), 128.3
(2!CH, Bn), 138.2 (C, Bn), 138.7 (C]CH), 212.5 (C]O).
Anal. Calcd for C17H24O4: C, 69.84; H, 8.27. Found: C,
69.48; H, 8.23.
2859, 1738, 1451, 1393, 1259, 1158, 1024, 972, 756 cmK1
.
1H NMR (300 MHz): 1.15 (s, 3H); 1.34 (q, JZ7 Hz, 6H,
P[OCH2CH3]2); 1.40–1.52 (m, 1H); 1.66 (s, 3H); 1.68–1.82
(m, 1H); 2.05–2.18 (m, 1H); 2.34–2.47 (m, 1H); 2.95 (dd,
J1Z29 Hz, J2Z14 Hz, 1H, CH2-P); 3.02 (dd, J1Z30 Hz,
J2Z14 Hz, 1H, CH2-P); 3.26 (d, JZ7 Hz, 1H, ex); 3.45 (t,
JZ9 Hz, 1H, ex); 3.73 (s, 1H, ex); 3.99 (d, JZ11 Hz, 1H);
4.02 (d, JZ7 Hz, 2H); 4.15 (app. sextet, JZ7 Hz, 2!2H,
P[OCH2CH3]2); 4.42 (d, JZ11 Hz, 1H); 4.51 (s, 2H); 5.42
(t, JZ7 Hz, 1H); 7.20–7.32 (m, 5H, Ar). 13C NMR
(75 MHz): 16.2 (P[OCH2CH3]2), 16.3 (CH3), 16.6 (CH3),
20.7 (CH2), 29.2 (CH2-P), 36.7 (CH2), 63.1
(P[OCH2CH3]2), 66.5 (CH2), 69.9 (CH2), 72.1 (CH2), 72.9
(C), 76.1 (CH), 121.1 (C]CH), 127.5 (CH, Bn), 127.7 (2!
CH, Bn), 128.3 (2!CH, Bn), 138.4 (C, Bn), 140.1
(C]CH), 165.5 (PCH2C]O). HRMS calcd for
C23H37NaO8P (MNaC) 495.2124, found 495.2123.
Compound 11a: [a]2D3 C5.41 (c 0.44, CHCl3). IR (film):
3402 (br), 2994, 2932, 2862, 1731, 1448, 1395, 1261, 1112,
1
1029, 974, 752 cmK1. H NMR (300 MHz): 1.10 (s, 3H);
1.35 (t, JZ7 Hz, 6H, P[OCH2CH3]2); 1.64 (s, 3H); 1.65–
1.77 (m, 1H); 1.89–2.15 (m, 3H); 2.95 (dd, J1Z29 Hz, J2Z
14 Hz, 1H, CH2-P); 3.02 (dd, J1Z30 Hz, J2Z14 Hz, 1H,
CH2-P); 3.32 (d, JZ12 Hz, 1H); 3.65 (d, JZ12 Hz, 1H);
4.01 (d, JZ7 Hz, 2H); 4.17 (app. double sextet, JZ3 Hz,
2!2H, P[OCH2CH3]2); 4.51 (s, 2H); 4.88 (d, JZ9 Hz, 1H);
5.42 (t, JZ7 Hz, 1H); 7.20–7.32 (m, 5H, Ar). 13C NMR
(75 MHz): 16.2 (P[OCH2CH3]2), 16.4 (CH3), 18.8 (CH3),
26.6 (CH2), 29.6 (CH2-P), 36.2 (CH2), 63.1
(P[OCH2CH3]2), 66.5 (CH2), 72.1 (CH2), 73.4 (C), 78.0
(CH), 121.6 (C]CH), 127.5 (CH, Bn), 127.7 (2!CH, Bn),
128.3 (2!CH, Bn), 138.4 (C, Bn), 139.1 (C]CH), 166.2
(PCH2C]O). HRMS calcd for C23H37NaO8P (MNaC)
495.2124, found 495.2122.
4.1.5. (C)-(2S,3R,6E)-2,2-Dimethyl-propionic acid 8-
benzyloxy-2,3-dihydroxy-2,6-dimethyl-oct-6-enyl ester
(10d). To a solution of hydroxyepoxide 6 (2.37 g,
8.58 mmol) in anh. dichloromethane (20 mL) at rt under
inert atmosphere (N2) were added pivalic acid (2.53 g,
24.7 mmol) and titanium tetraisopropylate (3.00 mL,
9.7 mmol). The reaction mixture was stirred overnight (ca.
12 h) at rt. The reaction mixture was quenched by a 5% HCl
solution (50 mL), extracted with chloroform (2!100 mL),
washed with water (2!25 mL) and saturated NaHCO3 (2!
25 mL), dried (Na2SO4) and evaporated to give the title
compound as pale yellow oil (2.99 g, 7.89 mmol, 92%).
[a]2D1 C17.82 (c 2.96, CHCl3). IR (film): 2970, 2933, 2862,
1727, 1462, 1369, 1286, 1167, 1073, 931, 742, 689 cmK1
.
1H NMR (300 MHz): 1.17 (s, 3H); 1.22 (s, 9H); 1.40–1.55
(m, 1H); 1.65 (s, 3H); 1.67–1.78 (m, 1H); 2.06–2.17 (m,
1H); 2.27–2.51 (m, 1HCs, 1H, ex); 3.41 (d, JZ8 Hz, 1H);
4.00 (d, JZ12 Hz, 1H); 4.02 (d, JZ7 Hz, 2H); 4.27 (d, JZ
12 Hz, 1H); 4.51 (s, 2H); 5.42 (t, JZ7 Hz, 1H); 7.27–7.37
(m, 5H, Ar). 13C NMR (75 MHz): 16.4 (CH3), 20.5 (CH3),
27.2 (3!CH3, t-Bu), 28.8 (CH2), 36.6 (CH2), 38.9 (C), 66.4
(CH2), 68.4 (CH2), 72.1 (CH2), 73.9 (C), 75.5 (CH), 121.4
(CH), 127.5 (CH, Bn), 127.7 (2!CH, Bn), 128.3 (2!CH,
4.1.7. (K)-(2S,6E)-(Diethoxy-phosphoryl)-acetic acid
8-benzyloxy-2-hydroxy-2,6-dimethyl-3-oxo-oct-6-enyl
ester (13). To a solution of keto diol 12 (2.70 g, 9.23 mmol)
in anh. dichloromethane (35 mL) at rt were added neat diethyl
phosphonoacetic acid (1.85 g, 9.23 mmol) and a solution of
DCC (2.31 g, 9.23 mmol) in anh. dichloromethane (10 mL).