I. Izquierdo et al. / Tetrahedron: Asymmetry 12 (2001) 293–300
299
4.13. (R)-3-O-Benzyl-1,3-butanediol 18
(20 mL) with 10% Pd–C (60 mg) as above gave 21 (1.21
g, 92.4%), after column chromatography (ether/hexane,
max
film
A solution of 17 (11.2 g, 26.5 mmol) in water/acetic
acid/methanol 3:4:3 (100 mL) was heated at 50°C for
2.5 h. TLC (ether/hexane, 1:4) indicated that a more
polar product had formed. The mixture was concen-
trated and repeatedly co-distilled with water. The distil-
lation residue was further purified by chromatography
1:2): GLC analysis (C) tR 7.09 min; [h]2D6 −16 (c 1); w
1743 and 1716 cm−1 (CꢀO). NMR data: H, 7.39–7.26
(m, 5H, PhCH2), 4.60 and 4.46 (2 d, 2H, J=11.7 Hz,
1
PhCH2), 3.70 (s, 3H, CO2Me), 3.54 (sext., 1H, J7,8
=
J
7%,8=J8,9=6.1 Hz, H-8), 2.72 (t, 2H, J2,3=6.3 Hz,
H-3,3), 2.60 (t, 2H, H-2,2), 2.47 (t, 2H, J5,6=7.2 Hz,
H-5,5), 1.78–1.41 (m, 4H, H-6,6%,7,7%), and 1.22 (d, 3H,
H-9,9,9); 13C, 208.88 (C-4), 173.33 (C-1), 139.09,
128.40, 127.74, and 127.49 (PhCH2), 74.59 (C-8), 70.42
(PhCH2), 51.83 (CO2CH3), 42.71, 37.09 and 36.14 (C-
3,5,7), 27.81 (C-2), 19.91 (C-6), and 19.60 (C-9). Mass
spectrum (LSIMS): m/z: found 315.2 (M++Na).
(ether/hexane, 1:5) to afford 18 as a colorless syrup
film
(3.35 g, 70%): [h]2D4 −57.5 (c 1); w
3421 (OH), 3066,
max
and 3031 cm−1 (aromatic). NMR data: 1H, 7.33 (bs, 5H,
PhCH2), 4.62 and 4.43 (2 d, 2H, J =11.6 Hz, PhCH2),
3.76 (m, 3H, H-1,1%,3), 1.77 (m, 2H, H-2,2%) and 1.25 (d,
3H, J3,4=6.1 Hz, H-4,4,4); 13C, 138.44, 128.52, 127.78,
and 127.74 (PhCH2), 74.63 (C-3), 70.48 (PhCH2), 60.87
(C-1), 38.82 (C-2), and 19.41 (C-4). Mass spectrum
(LSIMS): m/z: found 203.1 (M++Na).
4.16. Methyl (R)-8-benzyloxy-4-oxononanoate ethyl-
idenedithioketal 22
4.14. Methyl (E,R)-8-benzyloxy-4-oxo-5-nonenoate 20
To a stirred solution of 18 (1.44 g, 8 mmol) in dry
To an ice-water cooled and stirred mixture of 21 (1.21
g, 4.14 mmol) and ethanedithiol (0.92 mL, 10.9 mmol),
F3B·OEt2 (0.45 mL, 3.6 mmol) was added. The cooling
bath was removed and the reaction mixture was
allowed to warm to room temperature. After 30 min
GLC (C) revealed that 21 was completely consumed
and a new product had formed (tR 11.68 min). The
reaction mixture was diluted with ether and washed
with aqueous 10% sodium hydroxide, water and then
concentrated. Column chromatography (ether/hexane,
,
dichloromethane (20 mL), molecular sieves (4 A, pow-
der, 3.5 g) and PCC (3.5 g) were added at room
temperature. After 30 min, GLC (E) then revealed the
absence of 18 (tR 3.95 min) and the presence of a new
compound (tR 3.45 min). The mixture was diluted with
ether (50 mL), filtered through a silica gel pad, thor-
oughly washed with ether, and the combined filtrate
and washings concentrated to a residue that was perco-
lated (ether/hexane, 1:2) to afford presumably (R)-3-O-
benzyl-3-hydroxylbutanal 19 as a clear mobile oil (1.02
1:7) of the residue afforded 22 as a colorless mobile oil
film
max
(1.33 g, 87%): [h]2D5 −13 (c 1); w
1740 cm−1 (CꢀO).
1
NMR data: H, 7.39–7.26 (m, 5H, PhCH2), 4.60 and
4.49 (2 d, 2H, J=11.8 Hz, PhCH2), 3.70 (s, 3H,
CO2Me), 3.55 (sext., 1H, J7,8=J7%,8=J8,9=6.1 Hz, H-8),
3.28 (s, 4H, S(CH2)2S), 2.63 (bt, 2H, H-3,3%), 2.24 (bt,
2H, H-2,2%), 1.92 (bt, 2H, H-5,5%), 1.73–1.43 (m, 4H,
H-6,6%,7,7%), and 1.23 (d, 3H, H-9,9,9); 13C, 173.92
(C-1), 139.14, 128.40, 127.77, and 127.47 (PhCH2),
70.93 (C-4), 70.66 (C-8), 70.46 (PhCH2), 51.71
(CO2CH3), 40.08 (S(CH2)2S), 44.64, 37.66 and 36.72
(C-3,5,7), 31.55 (C-2), 22.87 (C-6), and 19.74 (C-9).
Mass spectrum (LSIMS): m/z: 391.13776 (M++Na) for
C19H28NaO3S2 391.13776 (deviation 0.0 ppm).
g, 72%): [h]2D4 −35 (c 1.4) [lit.20a [h]D −29.8 (c 1.36,
film
max
dichloromethane), lit.20b [h]D25 −36.5 (c 1)]; w
1726
cm−1 (CO).
Compound 19 (1 g, 5.62 mmol) was dissolved in
dichloromethane (15 mL) and treated with a solution of
(3-methoxycarbonylpropionyl)methylenetriphenylphos-
phorane17 (11, 2.5 g, 6 mmol) in the same solvent (15
mL), and the mixture stirred under reflux for 3 d. GLC
(E) then showed the presence of a new compound (tR
12.0 min). The reaction mixture was supported on silica
gel and chromatographed (ether/hexane, 1:3) to yield
the title compound 20 as a syrup (1.32 g, 80%): GLC
4.17. (R)-8-O-Benzyl-1,8-dihydroxy-4-nonanone ethyl-
analysis (C) tR 7.80 min; [h]2D5 −5.7 (c 1); w
1745,
idenedithioketal 23
film
max
1734, 1699, 1679 and 1635 cm−1 (CꢀO and CꢀC). NMR
1
data: H, 7.33 (m, 5H, PhCH2), 6.75 (dt, 1H, J5,6=16,
To a stirred suspension of LiAlH4 (280 mg, 7.37 mmol)
in anhydrous ether (10 mL) a solution of 22 (1.3 g, 3.53
mmol) in the same solvent (20 mL) was added dropwise
and the mixture refluxed for 1 h. TLC (ether/hexane,
1:2) then showed the presence of a more polar product.
The reaction mixture was quenched by cautious addi-
tion of aqueous 10% ammonium chloride, the organic
phase separated and the aqueous extracted with ether
(3×20 mL). The combined extracts were concentrated
J
6,7=J6,7%=7.3 Hz, H-6), 6.15 (dt, 1H, J5,7=J5,7%=1.4
Hz, H-5), 4.58 and 4.47 (2 d, 2H, J=11.8 Hz, PhCH2),
3.68 (s, 3H, CO2Me), 3.67 (sext., 1H, J7,8=J7%,8=J8,9
=
6.1 Hz, H-8), 2.87 (t, 2H, J2,3=6.7 Hz, H-3,3), 2.62 (t,
2H, H-2,2), 2.49 (dddd, 1H, H-7), 2.4 (dddd, 1H,
J7,7%=12.8 Hz, H-7%), and 1.23 (d, 3H, H-9,9,9); 13C,
198.00 (C-4), 173.41 (C-1), 144.04 (C-6), 131.97 (C-5),
138.52, 129.03, 128,48, and 127.73 (PhCH2), 73.56 (C-
8), 70.58 (PhCH2), 51.85 (CO2CH3), 39.65 and 34.48
(C-3,7), 27.85 (C-2), and 19.76 (C-9). Mass spectrum
(LSIMS): m/z: 313.14105 (M++Na) for C17H22NaO4
313.14158 (deviation 1.7 ppm).
and the residue chromatographed (ether/hexane, 1:1) to
film
max
yield 23 (1.1 g, 92%): [h]2D6 −12 (c 1); w
3421 cm−1
1
(OH). NMR data: H, 7.38–7.29 (m, 5H, PhCH2), 4.60
and 4.44 (2 d, 2H, J=11.8 Hz, PhCH2), 3.68 (t, 2H,
J
1,2=6.4 Hz, H-1,1), 3.56 (sext., 1H, J7,8=J7%,8=J8,9=
4.15. Methyl (R)-8-benzyloxy-4-oxononanoate 21
6.1 Hz, H-8), 3.30 (s, 4H, S(CH2)2S), 2.03–1.44 (3 m,
11H, H-2,2%,3,3%,5,5%,6,6%,7,7%, OH), and 1.24 (d, 3H,
H-9,9,9); 13C, 139.17, 128.41, 127.76, and 127.49
Hydrogenation of 20 (1.3 g, 4.48 mmol) in methanol