C. Della Monica et al. / Tetrahedron: Asymmetry 14 (2003) 3371–3378
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diethyl ether in petroleum ether) to give 14 (0.432 g;
89%). Rf=0.3 (30% diethyl ether in petroleum ether).
1H NMR (CDCl3): l 0.99 (3H, d, J=6.7 Hz, -CHCH3),
1.20 (3H, s, -C(CH3)CH3), 1.24 (3H, s, -C(CH3)CH3),
2.36 (1H, m, CH2=CH-CH-), 3.58 (1H, d, J=5.7 Hz,
-CH-OH), 3.66 (3H, s, -COOCH3), 4.93 (1H, d, J=10.3
Hz, HCH=CH-), 4.99 (1H, d, J=17.2 Hz, HCH=CH-
), 5.74 (1H, m, CH2=CH-). 13C NMR (CDCl3): l 15.7,
22.4, 22.7, 41.1, 46.3, 51.8, 79.5, 113.9, 142.1, 178.2.
HR-EIMS m/z 186.1260 (M+) (calcd 186,1256 for
C10H18O3). [h]2D5=+12.2 (c 1.0, CHCl3).
pyridine (0.046 ml, 0.57 mmol) a catalytic amount of
DMAP and (S)-MTPA-Cl (0.021 ml, 0.11 mmol) were
added. The reaction was stirred for 1 h at room temper-
ature. The solvents were then removed under N2 stream
and the crude residue was flash-chromatographed (5–
10% diethyl ether in petroleum ether) to give 14c (0.013
1
g). H NMR (CDCl3): l 0.98 (6H, s, -C(CH3)2), 1.10
(3H, d, J=6.9 Hz -CHCH3), 2.52 (1H, m, CH2=CH-
CH-), 3.24 (1H, d, J=6.5 Hz, -CH-OBn), 3.54 (3H, s,
-OCH3), 4.07 (1H, d, J=10.6 Hz, -CHHOOC), 4.25
(1H, d, J=11.3 Hz, -CH-O-CHH-Ph), 4.29 (1H, d,
J=10.6 Hz, -CHHOOC-), 4.52 (1H, d, J=11.3 Hz,
-CH-O-CHH-Ph), 4.93 (1H, d, J=10.5 Hz, HCH=
CH), 4.98 (1H, d, J=17.2 Hz, HCH=CH), 5.85 (1H,
m, CH2=CH-), 7.40 (10H, m, -OCH2-C6H5+-OOC-C-
C6H5).
4.9.
(3S,4R)-3-Benzyloxy-2,2,4-trimethyl-hex-5-enoic
acid methyl ester 14a
Compound 14 (0.100 g, 0.540 mmol) was dissolved in
dry acetonitrile (2.0 ml) and benzyl bromide (0.260 g,
1.60 mmol) in a reacti-vial in the dark. Ag2O (0.174 g,
0.80 mmol) was added. The mixture was refluxed and
stirred overnight, then filtered and concentrated. Flash
chromatography of the residue (1–30% diethyl ether in
4.12. Mosher ester 14d
To a solution of 14b (0.006 g, 0.023 mmol) in dry
pyridine (0.046 ml, 0.57 mmol) a catalytic amount of
DMAP and (R)-MTPA-Cl (0.021 ml, 0.11 mmol) were
added. The reaction was stirred for 1 h at room temper-
ature. The solvents were then removed under N2 stream
and the crude residue was flash-chromatographed (5–
10% diethyl ether in petroleum ether) to give 14d (0.013
g). 1H NMR (CDCl3): l 0.97 (3H, s, -C(CH3)CH3), 0.98
(3H, s, -C(CH3)CH3), 1.09 (3H, d, J=6.9 Hz,
-CHCH3), 2.51 (1H, m, CH2=CH-CH-), 3.23 (1H, d,
J=6.5 Hz, -CH-OBn), 3.53 (3H, s, -OCH3), 4.16 (1H,
d, J=10.6 Hz, -CHHOCO), 4.25 (1H, d, J=11.3 Hz,
-CH-O-CHH-Ph), 4.32 (1H, d, J=10.6 Hz,
-CHHOCO-), 4.57 (1H, d, J=11.3 Hz, -CH-O-CHH-
Ph), 4.93 (1H, d, J=10.5 Hz, HCH=CH), 4.98 (1H, d,
J=17.2 Hz, HCH=CH), 5.85 (1H, m, CH2=CH-),
7.40 (10H, m, -OCH2-C6H5+-OOC-C-C6H5).
1
petroleum ether) gave 14a (0.046 g, 31%) as an oil. H
NMR (CDCl3): l 1.13 (3H, d, J=6.7 Hz, -CHCH3),
1.19 (3H, s, -C(CH3)CH3), 1.28 (3H, s, -C(CH3)CH3),
2.43 (1H, m, CH2=CH-CH-), 3.60 (3H, s, -COOCH3),
3.66 (1H, d, J=6.5 Hz, -CH-OBn), 4.54 (1H, d, J=
12.9 Hz, -CH-O-CHH-Ph), 4.67 (1H, d, J=12.9 Hz,
-CH-O-CHH-Ph), 4.91 (1H, d, J=10.2 Hz, HCH=
CH-), 5.00 (1H, d, J=17.2 Hz, HCH=CH), 5.71 (1H,
m, CH2=CH-), 7.36 (5H, m, -OCH2-C6H5). HR-EIMS
m/z 276.1730 (M+) (calcd 276,1725 for C11H18O5).
4.10. (3S,4R)-3-Benzyloxy-2,2,4-trimethyl-hex-5-en-1-ol
14b
To a solution of 14a (0.046 g, 0.17 mmol) in dry THF
(1.0 ml), at 0°C, LiAlH4 (1 M in THF, 0.510 ml, 0.510
mmol) was added dropwise. The reaction mixture was
stirred at the same temperature for 1 h and the
quenched with ethyl acetate. The solution was then
treated with 30% aq. NH4OH (2.0 ml). The suspension
was filtered on a pad of Celite® washing with ethyl
acetate. Solvents were removed in vacuo and the
residue was flash-chromatographed (10–30% diethyl
ether in petroleum ether) to give 14b (0.017 g, 41%).
Rf=0.4 (30% diethyl ether in petroleum ether). 1H
NMR (CDCl3): l 0.92 (3H, s, -C(CH3)CH3), 0.99 (3H,
s, -C(CH3)CH3), 1.17 (3H, d, J=6.9 Hz, -CHCH3), 2.58
(1H, m, CH2=CH-CH-), 3.33 (1H, d, J=10.9 Hz,
-CHHOH), 3.35 (1H, d, J=6.5 Hz, -CH-OBn), 3.55
(1H, d, J=10.9 Hz, -CHHOH), 4.45 (1H, d, J=11.1
Hz, -CH-O-CHH-Ph), 4.65 (1H, d, J=11.1 Hz, -CH-O-
CHH-Ph), 4.98 (1H, d, J=10.5 Hz, HCH=CH-), 5.04
(1H, d, J=17.2 Hz, HCH=CH), 5.96 (1H, m, CH2=
CH-), 7.30 (5H, m, -OCH2-C6H5). 13C NMR (CDCl3):
l 15.0, 20.9, 23.7, 38.5, 40.5, 71.3, 74.7, 89.6, 112.8,
127.7 (×3), 128.4 (×2), 138.1, 145.2. HR-EIMS m/z
248.1780 (M+) (calcd 248,1776 for C16H24O2). [h]2D5=
+29.8 (c 1.0, CHCl3).
4.13. (3S,4S)-3-Hydroxy-2,2,4-trimethyl-5-oxo-
pentanoic acid methyl ester 15
A stream of O2/O3 was bubbled through a solution of
14 (0.290 g, 1.50 mmol) in dry CH2Cl2 (40.0 ml) at
−78°C until a faint blue color persisted. A stream of
argon was then bubbled through the solution until it
became colorless. Triphenylphosphine (0.490 g, 1.90
mmol) was added and the mixture was allowed to warm
to room temperature and stir overnight. The solution
was then concentrated and the residue was flash-chro-
matographed (30–70% diethyl ether in petroleum ether)
to give 15 (0.226 g, 80%). Rf=0.20 (50% diethyl ether in
petroleum ether). 1H NMR (CDCl3): l 1.04 (3H, d,
J=7.1 Hz, -CHCH3), 1.18 (3H, s, -C(CH3)CH3), 1.28
(3H, s, -C(CH3)CH3), 2.51 (1H, m, CHO-CH-), 3.45
(1H, d, J=7.9 Hz, -OH), 3.68 (3H, s, COOCH3), 4.13
(1H, dd, J=7.9, 3.5 Hz, -CH-OH), 9.61 (1H, s, OHC-).
13C NMR (CDCl3): l 7.9, 21.7, 24.0, 45.8, 48.6, 52.2,
74.9, 178.0, 203.6. HR-EIMS m/z 188.1045 (M+) (calcd
188,1049 for C9H16O4). [h]2D5=13.8 (c 1.0, CHCl3).
4.14. (2-Oxo-pentyl)-phosphonic acid diethyl ester 16
4.11. Mosher ester 14c
To a stirred solution of diethylmethylphosphonate (1.30
To a solution of 14b (0.006 g, 0.023 mmol) in dry
g, 8.30 mmol) in dry THF (2.0 ml) at −78°C, under N2,