FEATURE ARTICLE
Synthesis of (–)-(3S,6R)-3,6-Dihydroxy-10-methylundecanoic Acid
1221
HRMS (ESI): m/z calcd for C15H32OSi + Na [M + Na]+: 279.2120;
1 H), 4.49 (d, J = 6.8 Hz, 1 H), 4.65 (d, J = 6.8 Hz, 1 H), 5.15–5.26
found: 279.2127.
(m, 2 H), 5.62–5.75 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 37.7, 55.5, 59.6, 75.9, 93.8, 117.3,
(3R)-5-(Tetrahydro-2H-2-pyranyloxy)pent-1-en-3-ol (11)
To a stirred solution of 6 (1.5 g, 7.41 mmol) in Et2O–MeCN (3:1,
20 mL) were added TPP (2.92 g, 11.12 mmol) and imidazole (1.26
g, 18.50 mmol) at 0 °C and the mixture stirred for 5 min. I2 (2.82 g,
22.20 mmol) was added at 0 °C and stirred for 1 h. The reaction
mixture was quenched with sat. aq Na2S2O3 (10 mL) and extracted
with EtOAc (3 × 10 mL). The combined organic layers were washed
with H2O (10 mL), brine (10 mL), and dried (Na2SO4). The solvent
was evaporated in vacuo to afford the crude iodo compound. This
was used for the next step without further purification. To a stirred
solution of the above iodo compound in EtOH (20 mL) was added
activated Zn dust (0.98 g, 14.98 mmol) and the mixture stirred at re-
flux for 1–2 h. The mixture was passed through a short pad of
Celite. The filtrate was concentrated and the residue was purified by
column chromatography on silica gel (eluent: PE–EtOAc, 1:1) to
afford 11 (1.09 g, 80%) as a colorless liquid; yield: 1.09 g (80%);
Rf = 0.2 (PE–EtOAc, 1:1); [a]D25 –9.6 (c 3.75, CHCl3).
137.6.
ESIMS: m/z = 169.0 [M + Na]+.
HRMS (ESI): m/z calcd for C7H14O3 + Na [M + Na]+: 169.0840;
found: 169.0846.
(3R)-3-(Methoxymethoxy)pent-4-enoic acid (14)
To an ice-cooled solution of 2-iodoxybenzoic acid (1.53 g, 5.46
mmol) in DMSO (4 mL) was added a solution of 13 (0.4 g 2.73
mmol) in anhyd CH2Cl2 (5 mL). The mixture was stirred at r.t. for 5
h and then filtered through a Celite pad (1 g) and washed with
CH2Cl2 (4 × 50 mL). The combined organic filtrates were washed
with H2O (2 × 5 mL) and brine (2 × 4 mL), dried (Na2SO4), and
concentrated in vacuo to afford the crude aldehyde. This was used
for the next step without further purification. To a stirred solution of
the above aldehyde in t-BuOH–2-methylbut-2-ene (2:1, 3 mL) were
added NaClO2 (0.208 g, 2.73 mmol), and NaH2PO4·2H2O (0.43 g,
2.75 mmol) [dissolved in H2O (0.5 mL)] and stirred for 6 h at r.t.
The solvent was removed under reduced pressure and extracted
with EtOAc (2 × 5 mL). The combined organic layers were washed
with brine (2 mL) and dried (Na2SO4). The solvent was evaporated
and the residue was purified by column chromatography on silica
gel (eluent: PE–EtOAc, 7:3) to afford the acid 14 as a colorless liq-
1H NMR (300 MHz, CDCl3): d = 1.39–1.91 (m, 8 H), 2.26 (br s, 1
H, OH), 3.69–3.88 (m, 2 H), 4.06–4.17 (m, 1 H), 4.58 (t, J = 3.02
Hz, 1 H), 5.07 (d, J = 10.5 Hz, 1 H), 5.22 (d, J = 17.4 Hz, 1 H),
5.78–5.91 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 19.40, 25.3, 30.5, 36.2, 62.2, 65.6,
72.0, 98.9, 114.3, 140.5.
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uid; yield: 340 mg (78%); Rf = 0.2 (PE–EtOAc, 7:3); [a]D +57.4
ESIMS: m/z = 209.0 [M + Na]+.
(c 1.0, CHCl3).
HRMS (ESI): m/z calcd for C10H18O3 + Na [M + Na]+: 209.1153;
IR (neat): 2933, 1717, 1414, 1217, 1151, 1031 cm–1.
found: 209.1154.
1H NMR (500 MHz, CDCl3): d = 2.46–2.68 (m, 2 H), 3.33 (s, 3 H),
4.44–4.53 (m, 2 H), 4.64–4.68 (m, 1 H), 5.24 (d, J = 10.4 Hz, 1 H),
5.32 (d, J = 16.6 Hz, 1 H), 5.68–5.76 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 40.7, 55.5, 73.5, 93.8, 118.5,
136.2, 176.3.
ESIMS: m/z = 183 [M + Na]+.
HRMS (ESI): m/z calcd for C7H12O4 + Na [M + Na]+: 183.0633;
2-[(3R)-3-(Methoxymethoxy)pent-4-enyl]oxytetrahydro-2H-
pyran (12)
To a cooled (0 °C) solution of the above compound 11 (1.0 g, 5.37
mmol) in CH2Cl2 (10 mL) were added sequentially DIPEA (1.75
mL, 10.77 mmol) and MOMCl (0.45 mL, 5.87 mmol) and the mix-
ture stirred at r.t. for 2 h. The mixture was evaporated and the resi-
due purified by column chromatography on silica gel (eluent: PE–
EtOAc, 8:2) to afford 12 as a colorless liquid; yield: 1.13 g (92%);
Rf = 0.65 (PE–EtOAc, 8:2); [a]D25 +35.8 (c 1.4, CHCl3).
found: 183.0630.
(3R)-3-Hydroxypent-4-enoic Acid (4)
IR (neat): 3078, 2939, 2881, 1636, 1441, 1353, 1030, 987, 920, 869
cm–1.
To a stirred solution of compound 14 (0.25 g, 0.70 mmol) in MeOH
(5 mL) was added PTSA (10 mol%) and the reaction mixture was
stirred at r.t. for 4 h. The MeOH was removed under reduced pres-
sure and the crude product was purified by column chromatography
on silica gel (eluent: PE–EtOAc, 6:4) to afford the acid 4 as a vis-
cous liquid; yield: 140 mg (81%); Rf = 0.35 (PE–EtOAc, 6:4);
[a]D25 +4.1 (c 0.75, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.47–1.69 (m, 6 H), 1.70–1.90 (m,
2 H), 3.34 (s, 3 H), 3.37–3.52 (m, 2 H), 3.72–3.88 (m, 2 H), 4.14
(app pent, J = 6.8 Hz, 1 H), 4.49 (d, J = 6.8 Hz, 1 H), 4.55 (q,
J = 4.5 Hz, 1 H), 4.66 (d, J = 6.0 Hz, 1 H), 5.15–5.27 (m, 2 H),
5.61–5.75 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 19.5, 25.4, 30.7, 35.5, 62.2, 63.8,
74.3, 74.7, 93.8, 98.9, 117.1, 138.1.
IR (neat): 3417, 1719, 1403, 1288, 1136, 1038, 939 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.56–2.62 (m, 2 H), 4.50–4.58 (m,
1 H), 5.17 (dt, J = 10.5, 1.5 Hz, 1 H), 5.33 (dt, J = 17.3, 1.5 Hz, 1
H), 5.81–5.94 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 40.9, 68.9, 115.8, 138.3, 176.3.
ESIMS: m/z = 139 [M + Na]+.
ESIMS: m/z = 253.0 [M + Na]+.
HRMS (ESI): m/z calcd for C12H22O4 + Na [M + Na]+: 253.1415;
found: 253.1426.
(3R)-3-(Methoxymethoxy)pent-4-en-1-ol (13)
HRMS (ESI): m/z calcd for C5H8O3 + Na [M + Na]+: 139.0371;
found: 139.0367.
To a stirred solution of compound 12 (1.0 g, 4.34 mmol) in MeOH
(8 mL) was added PPTS (10 mol%, cat.) and the mixture was stirred
at r.t. for 4 h. The MeOH was removed under reduced pressure and
the crude product was purified by silica gel column chromatography
(eluent: PE–EtOAc, 8:2) to afford 13 as a viscous liquid; yield: 530
mg (85%); Rf = 0.55 (PE–EtOAc, 8:2); [a]D +100.6 (c 0.9,
CHCl3).
IR (neat): 3424, 2945, 1643, 1423, 1151, 1096, 1030, 922 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.77 (t, J = 6.0 Hz, 2 H), 2.40 (br
s, 1 H, OH), 3.36 (s, 3 H), 3.63–3.80 (m, 2 H), 4.21 (q, J = 7.5 Hz,
(3R,4E,6R)-6-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-3-hydroxy-
10-methylundec-4-enoic Acid (16)
Grubbs II catalyst (0.025 g, 0.03 mmol, 5 mol%) was dissolved in
CH2Cl2 (1 mL) and added dropwise to a solution of the compound
4 (0.07 g, 0.60 mmol) and compound 3 (0.18 g, 0.70 mmol) in
CH2Cl2 (1 mL) at r.t. After completion of addition, the reaction mix-
ture was allowed to reflux for 1 h. The solvent was removed under
reduced pressure and the crude product was purified by silica gel
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Synthesis 2010, No. 7, 1217–1222 © Thieme Stuttgart · New York