F. Yang et al. / Tetrahedron 69 (2013) 9463e9468
9467
4.7. (4S)-5-Benzyloxy-4-methoxypentan-1-al27
concentrated under reduced pressure. The residue was purified by
flash column chromatography over silica gel (petroleum ether/
ethyl acetate 4:1) to provide the title compound as colorless oil
(5.0 g, 93%). The 1H NMR spectrum was identical to literature data.
To a solution of oxalyl chloride (0.84 mL, 9.6 mmol) in methy-
lene chloride (10 mL) at ꢀ78 ꢁC was added dimethyl sulfoxide
(1.4 mL, 19.2 mmol). After stirring for 20 min, the above-obtained
alcohol (0.53 g, 2.4 mmol) in methylene chloride (3.0 mL) was
added dropwise. The mixture was stirred for 20 min. Triethylamine
(5.1 mL, 36 mmol) was added, and the reaction was allowed to
warm up to room temperature. Water (20 mL) was added, and the
aqueous phase was extracted with dichloromethane (10 mLꢂ2).
The combined organic layers were dried over MgSO4, filtered, and
concentrated under reduced pressure. The residue was purified by
flash column chromatography over silica gel (petroleum ether/
ethyl acetate 5:1) to provide the title compound as colorless oil
1H NMR (400 MHz, CDCl3)
d
9.67 (d, J¼1.4 Hz, 1H), 6.70 (t, J¼7.5 Hz,
1H), 4.18 (q, J¼7.1 Hz, 2H), 3.58e3.52 (m, 1H), 3.44 (s, 3H),
2.37e2.21 (m, 2H), 1.84 (s, 3H), 1.80e1.75 (m, 2H), 1.29 (t,
J¼7.1 Hz, 3H).
4.11. General procedure for chelation-controlled iso-
propenylation of a-oxygenated aldehydes
A commercial isopropenyl magnesium bromide solution (0.50 M
in THF, 5.0 equiv) was evaporated to dryness under reduced pres-
sure, and the residue was dissolved in anhydrous dichloromethane
under nitrogen. This operation was repeated twice, and the ob-
tained Grignard reagent solution in dichloromethane (0.50 M) was
combined with powdered anhydrous zinc chloride (2.5 equiv) at
0 ꢁC. The resulted gray suspension was stirred at room temperature
for 5 h, and then cooled to ꢀ78 ꢁC. A solution of the aldehyde in
anhydrous toluene (0.05 M) was added via cannula slowly. The
reaction was stirred at ꢀ78 ꢁC for 15 min and at 30 ꢁC until full
conversion was detected by TLC, at which point the reaction mix-
ture became a yellowish clear solution usually. Saturated aqueous
solution of ammonium chloride was added. The mixture was fil-
tered through Celite, and the aqueous phase was extracted with
ethyl acetate. The combined organic layers were dried over mag-
nesium sulfate, filtered, and concentrated under reduced pressure.
The crude residue was purified by flash column chromatography
over silica gel to provide the isopropenylated product.
(0.48 g, 92%). 1H NMR (400 MHz, CDCl3)
7.30e7.20 (m, 5H), 4.47 (s, 2H), 3.45e3.37 (m, 3H), 3.30 (s, 3H), 2.42
(dt, J¼7.1, 1.7 Hz, 2H), 1.86e1.75 (m, 2H).
d
9.66 (t, J¼1.7 Hz, 1H),
4.8. (5S)-Tetrahydro-5-methoxy-2H-pyran-2-ol (11)
To a solution of the above-obtained aldehyde (2.20 g, 9.9 mmol)
in methanol (25 mL) was added Pd/C (10% w/w, 0.77 g). The mixture
was stirred under hydrogen for 24 h, filtered through Celite, and
concentrated under reduced pressure. The crude product was used
in the next step without further purification.
A purified sample for spectral characterization was prepared by
flash column chromatography over silica gel (petroleum ether/
ethyl acetate 2:1) to provide the title compound as colorless oil
(w1:1 mixture of anomeric isomers). ½a D20
ꢃ
ꢀ9.0 (c 1.2, CHCl3). 1H
NMR (400 MHz, CDCl3) d 5.04e5.00 (m, 0.5H), 4.97e4.92 (m, 0.5H),
4.08e4.02 (br dd, J¼11.7, 2.9 Hz, 0.5H), 3.90e3.84 (br dd, J¼11.5,
6.5 Hz, 0.5H), 3.65e3.60 (br dd, J¼11.5, 3.4 Hz, 0.5H), 3.54e3.45 (m,
1.5H), 3.36 (s, 1.5H), 3.35 (s, 1.5H), 3.32e3.21 (m, 1H), 2.10e1.58 (m,
4.12. (6S,7S,2E)-Ethyl 6-methoxy-2,8-dimethyl-7-hydroxynon-
2-enoate (3)
3.5H),1.54e1.45 (m, 0.5H); 13C NMR (100 MHz, CDCl3)
d (93.4, 92.8),
(73.6, 73.5), (64.0, 63.8), (56.2, 56.0), (28.6, 27.6), (24.6, 23.8). ESI-
From aldehyde 4 (1.80 g, 8.69 mmol), the title compound was
MS m/z 155.0 ([MþNa]þ).
obtained as colorless oil (1.82 g, 85%, dr >20:1). ½a D20
þ18.1 (c 1.0,
ꢃ
CHCl3). 1H NMR (400 MHz, CDCl3)
d 6.72e6.60 (m, 1H), 5.00e4.97
4.9. (6S,2E)-Ethyl 6-methoxy-2-methyl-7-hydroxyhept-2-
(m, 1H), 4.92e4.89 (m, 1H), 4.14 (q, J¼7.1 Hz, 2H), 3.93 (d, J¼6.7 Hz,
1H), 3.39 (s, 3H), 3.24e3.18 (m, 1H), 2.64 (br s, 1H), 2.21 (q, J¼7.6 Hz,
2H), 1.79 (br s, 3H), 1.71 (br s, 3H), 1.64e1.48 (m, 2H), 1.24 (t,
J¼7.1 Hz, 3H). HRMS (TOF) found 279.1568 [MþNa]þ, calcd 279.1572
for C14H24O4. The diastereomeric ratio was determined by com-
paring the peak areas of 6-OCH3 (3.39 ppm for the major di-
astereomer, 3.37 ppm for the minor diastereomer), and 8-CH3
(1.71 ppm for the major diastereomer, 1.67 ppm for the minor
diastereomer).
enoate8
To a solution of the above-obtained crude lactol 11 (9.9 mmol) in
toluene (15 mL) was added (carbethoxyethylidene)triphenyl
phosphorane (7.2 g, 19.8 mmol, 2.0 equiv). The reaction mixture
was stirred at 80 ꢁC for 3 h. The mixture was cooled to room
temperature and concentrated under reduced pressure. The residue
was purified by flash column chromatography over silica gel (pe-
troleum ether/ethyl acetate 3:1) to provide the title compound as
colorless oil (1.66 g, 78% for two steps). The 1H NMR spectrum was
4.13. (3S,4S)-7-((tert-Butyldimethylsilyl)oxy)-4-methoxy-2-
methylhept-1-en-3-ol (18)
identical to literature data. 1H NMR (400 MHz, CDCl3)
d
6.74 (t,
J¼7.4 Hz, 1H), 4.19 (qd, J¼7.1, 1.9 Hz, 2H), 3.72 (dd, J¼11.4, 2.8 Hz,
1H), 3.51 (dd, J¼11.7, 5.8 Hz, 1H), 3.41 (s, 3H), 3.30e3.25 (m, 1H),
2.24 (dd, J¼14.9, 7.6 Hz, 2H), 1.84 (s, 3H), 1.77e1.68 (m, 1H),
1.66e1.57 (m, 1H), 1.30 (t, J¼7.1 Hz, 3H).
From aldehyde 14 (1.84 g, 7.5 mmol), the title compound was
obtained as colorless oil (1.80 g, 82%, dr 19:1). ½a D20
þ0.5 (c 0.4,
ꢃ
MeOH). 1H NMR (400 MHz, CDCl3)
d 5.08 (s, 1H), 5.03e5.00 (m, 1H),
4.95e4.92 (m,1H), 3.94 (d, J¼6.9 Hz,1H), 3.62e3.56 (m, 2H), 3.42 (s,
4.10. (6S,2E)-Ethyl 6-methoxy-2-methyl-7-oxohept-2-enoate
3H), 3.27e3.22 (m, 1H), 1.77e1.72 (m, 3H), 1.65e1.49 (m, 4H), 0.88
(4)8
(s, 9H), 0.04 (s, 6H). 13C NMR (100 MHz, CDCl3)
d 144.67, 114.07,
82.31, 77.58, 63.35, 58.14, 28.33, 26.55, 26.20, 18.58, 18.15, ꢀ5.05.
To a solution of oxalyl chloride (8.8 mL, 100 mmol) in methylene
chloride (100 mL) at ꢀ78 ꢁC was added dimethyl sulfoxide (14.3 mL,
200 mmol). After stirring for 20 min, the above-obtained alcohol
(5.40 g, 25 mmol) in methylene chloride (25.0 mL) was added
dropwise. The mixture was stirred for 20 min. Triethylamine
(53.3 mL, 275 mmol) was added, and the reaction was allowed to
warm up to room temperature. Water (120 mL) was added. The
aqueous phase was extracted with dichloromethane (30 mLꢂ2).
The combined organic layers were dried over MgSO4, filtered, and
HRMS (TOF) found 288.2127 [M]þ, calcd 288.2121 for C15H32O3Si.
4.14. (S)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2-
methylprop-2-en-1-ol (19)
From aldehyde 15 (1.49 g, 4.9 mmol), the title compound was
obtained as colorless oil (0.67 g, 80%, dr 17:1). ½a D20
þ0.17 (c 0.6,
ꢃ
MeOH). 1H NMR (400 MHz, CDCl3)
d 5.03 (s, 1H), 4.93e4.84 (m, 1H),
4.16e4.10 (m, 2H), 3.88 (d, J¼3.0 Hz, 1H), 3.87e3.85 (m, 1H), 2.59 (s,