Total partial synthesis of (3S, 6S)-(+)-3,7-dimethyl-6-hydroxy-3- acetoxyocta-1,7-diene and (3S, 6S)-(-)-3,7-dimethylocta-1,7-diene-3,6-diol from geraniol

Article abstract of DOI:10.1039/a809950b

The synthesis of (3S, 6S)-(+)-3,7-dimethyl-6-hydroxy-3-acetoxyocta-1,7- diene and (3S, 6S)-(-)3,7-dimethylocta-1,7-diene-3,6-diol via the rearrangement of the chiral 2,3-epoxy alcohol, with the system Ph₃P, pyridine, I₂ and H₂O, is described.

Full text of DOI:10.1039/a809950b

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324 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 324^325y
Total Partial Synthesis of (3S, 6S)-(‡)-3,7-
Dimethyl-6-hydroxy-3-acetoxyocta-1,7-diene and
(3S, 6S)-( )-3,7-Dimethylocta-1,7-diene-3,6-diol
from Geranioly
Zuosheng Liu,a Jiong Lan,a Yulin Li,*a Yacheng Xingb and
Wen Cenb
aNational Laboratory of Applied Organic Chemistry and Institute of Organic Chemistry,
Lanzhou University, Lanzhou 730000, P.R. China
bDepartment of Chemistry, Qingdao University, Qingdao, 266071, P.R. China
The
synthesis
of
(3S, 6S)-(‡)-3,7-dimethyl-6-hydroxy-3-acetoxyocta-1,7-diene
and
(3S, 6S)-( )-
3,7-dimethylocta-1,7-diene-3,6-diol via the rearrangement of the chiral 2,3-epoxy alcohol, with the system Ph3P,
pyridine, I2 and H2O, is described.
Compound 1,1 a novel monoterpenoid, has been isolated
from Mutisia spinosa (Compositae) and compound 2 has
been isolated from Cinnamonum camphora.2 The absolute
con¢gurations at C-3 and C-6 of 1 and 2 have not been
determined. Photooxidation of linalyl acetate and linalool4
gave 1 and 2, respectively. However the authors obtained
an isomeric mixture. To our knowledge, the asymmetric syn-
thesis of 1 and 2 has not been reported. Herein we report
the total synthesis of (3S, 6S)-(‡)-1 and (3S, 6S)-( )-2 from
geraniol 3 (Scheme 1).
Linalool 5 was protected with Ac2O, Et3N and DMAP,8
then SeO2 oxidation gave the allylic alcohol 6.9 Sharpless
asymmetric epoxidation5 of the allylic alcohol
5 with
l-(‡)-DET led to the (6S, 7S)- and (6R, 7R)-epoxy alcohols
in a ratio of ca. 10:1. Rearrangement of epoxy alcohol 7 gave
the title compound 1 in 90% yield. Treatment of 1 with
K2CO3 in MeOH give the diol 2 in 96% yield. As the authors
did not report the optical rotation of natural 1 and 2, we
could not determine the absolute con¢guration of C-3 and
C-6.
Experimental
i
O
IR spectra were recorded on a Nicolet FT 170SX as liquid ¢lms,
1H NMR spectra were recorded on a Bruker AC-80 or Bruker AM-400
spectrometer and 13C NMR spectra were recorded on a 100 MHz
spectrometer in CDCl3 solution using TMS as internal reference.
IR spectra were obtained using a FT 170SX (¢lm) spectrophotometer.
Mass spectra were measured on aVG ZAB-HS spectrometer by direct
inlet at 70 eV, and signals are given in m/z with relative intensity
(%) in parentheses. Optical rotation measurements were carried out
on a Jasco 20C polarimeter.
OH
OH
3
6
7
4
5
ii
OAc
OAc
OH
iii, iv
OH
OH
v
Rearrangement of Compound 4 to 5.öTo a stirred solution of
epoxy alcohol 1 (500 mg, 2.94 mmol) in dry Et2O^CH3CN (5:3,
16 mL) was added sequentially Ph3P (2.31g, 8.82 mmol), pyridine
(0.94 mL, 11.76 mmol), I2 (1.12 g, 4.41mmol) at 0 8C. After stirring
for 2 h at 0 8C, H2O (53 lL, 2.94 mmol) was added to the system.
The reaction mixture was re¯uxed for 10 h at 38 8C, then 20%
Na2S2O3 (aq) (2 mL) and saturated NaHCO3 (aq) (2 mL) were
added to quench the reaction and the organic layer extracted with
ether ꢀ3 Â 50 mL). The combined ether extracts were washed with
5% HCl ꢀ4 Â 10 mL), saturated NaHCO3 (10 mL), H2O and brine,
then dried. Evaporation of the solvent gave the residue, which was
¯ash chromatographed eluting with light petroleum±ethyl acetate
OAc
O
vi
7
6
3
1
OH
vii
1
OH
OH
2
20
(6:1 v/v) to afford 4 (445 mg, 98%) as a colorless oil. [aŠ ‡ 21:2 (c
Scheme 1 Reagents: i, ref. 5(b), 91%; ii, Ph3P, I2, pyridine,
Et2O^CH3CN (5:3), 0 8C, 1h, then 1 equiv. H2O, 38 8C, 10 h, 98%,
iii, Ac2O, Et3N, r.t., 10h, 70%; iv, SeO2, ButOOH, CH2Cl2, r.t., 2 h,
51%; v, Ti(OPri)4, ButOOH, L-(‡)-DET, CH2Cl2 , 4Ð M.S., CaH2,
silica gel, 40 to 20 8C, 5 h, 78%; vi, Ph3P, I2, pyridine,
Et2O^CH3CN (5:3), 0 8C, 1h, then 1 equiv. H2O, 38 8C, 6 h, 90%; vii,
K2CO3, MeOH, r.t., 2 h, 96%.
0.6, CHCl3); dH(400 MHz) (CDCl3): 5.91 (1H, dd, J ˆ 17D:3, 10.7 Hz,
CHˆ), 5.21 (1H, d, J ˆ 17:3 Hz,CHˆ), 5.11 (1H,
t
J ˆ 6:7 Hz
CHˆ), 5.07 (1H, d, J ˆ 10:7 Hz, CHˆ), 2.08^1.94 (2H, m, CH2), 1.68
(3H, s, CH3), 1.65 (3H, s, CH3), 1.58^1.50 (2H, m, CH2), 1.28 (3H,
s, CH3).
Acetylation and SeO2 Oxidation of Linalool 5.öA mixture of
linalool (445 mg, 2.9 mmol), triethylamine (0.61mL, 4.35 mmol), acetic
anhydride (0.41mL, 4.35 mmol) and DMAP (28 mg, 0.23 mmol) was
stirred at r.t. for 10 h. The mixture was extracted with ether
ꢀ3 Â 50 mL) and the organic layer was washed with 5% HCl
ꢀ4 Â 5 mL), saturated NaHCO3 (10 mL), H2O and brine, then dried.
Evaporation of the solvent gave the residue, which was £ash
chromatographed eluting with light petroleum^ethyl acetate (15:1 v/v)
to a¡ord linalyl acetate (400 mg, 70%) as a colorless oil. A solution of
linalyl acetate (400 mg, 2.04 mmol) in 5 mL CH2Cl2 was added to a
solution of SeO2 (113 mg, 1.02 mmol) and ButOOH (70%, 1.13 mL,
4.08 mmol) in 15 mL CH2Cl2 and the reaction mixture was stirred
at r.t. for 2 h. The mixture was extracted with ether ꢀ3 Â 50 mL)
and the organic layer washed with 10% KOH ꢀ4 Â 5 mL), saturated
NaHCO3 (10 mL), H2O and brine, then dried. Evaporation of the
solvent gave the residue which was £ash chromatographed eluting
with light petroleum^ethyl acetate (6:1 v/v) to a¡ord linalyl acetate
Geraniol
3 was epoxized by Sharpless asymmetric
epoxidation [l-(‡)-DET was employed].5 By our method,6
rearrangement of epoxide 4 gave linalool 5 in 98% yield
and > 95% e.e.7 Epoxide 4 was iodinated with Ph3P (3
equiv.), pyridine (4 equiv.) and I2 (1.5 equiv.) in dry diethyl
ether and CH3CN, then the iodide was converted to linalool
5 by addition of 1 equiv. H2O.
* To receive any correspondence ( e-mail: liyl@lzu.edu.cn).
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).

View Article Online
J. CHEM. RESEARCH (S), 1999 325
21
(210 mg, 51%) as
a
colorless oil. [aŠ ‡ 8:61 (c 2.4, CHCl3);
2.05^1.92 (m, 2H, CH2), 1.82^1.77 (m, 2H, CH2), 1.70 (s, 3H, CH3),
1.53 (s, 3H, CH3). dC(100 MHz, CDCl3): 169.93, 147.06, 141.51, 113.28,
111.29, 82.73, 75.77, 35.65, 28.68, 23.63, 22.33, 17.33.
D
dH(80 MHz) (CDCl3): 5.90 (dd, J ˆ 17:0, 10.8 Hz, 1H, CHˆ), 5.30
(t, J ˆ 6:4 Hz, 1H, CHˆ), 4.00 (s, 2H, CH2), 2.02 (s, 3H, CH3),
2.18^1.92 (m, 2H, CH2), 1.74^1.59 (m, 2H, CH2), 1.65 (s, 3H, CH3),
1.28 (s, 3H, CH3).
ꢀ
†-3,7-Dimethylocta-1,7-diene-3,6-diol (2).öA mixture of 1 (15 mg,
0.064 mmol) in methanol (1mL) and anhydrous K2CO3 (8 mg)
was stirred at r.t. for 2 h. The reaction mixture was diluted with
Et2O (30 mL), washed ꢀ2 Â 5 mL H2O, 5 mL brine), dried (anhydrous
Epoxidation of
6
to 7.öTo
a
mixture of Ti(OPi4† † (0.3 mL,
1mmol), CaH2 (15 mg), 4 Ð molecular sieves (40 mg) 4and silica
gel H (20 mg) in 8 mL dry CH2Cl2 was added l-(‡)-DET (0.21mL,
1.2 mmol) under Ar at 20 8C. After 10 min, the allylic alcohol
6 (210 mg, 1mmol) was added. The reaction mixture was stirred for
another 10 min and ButOOH (1.1 mL, 3.16 M in toluene, 2 mmol)
was added at 40 8C. After 8 h at 20 8C, 2 mL 10% aqueous
tartaric acid was added. After stirring for 1 h, the mixture was
extracted with ether ꢀ3 Â 50 mL) and the organic layer was washed
with 10% KOH ꢀ2 Â 10 mL), saturated NaHCO3 (10 mL), H2O
and brine, then dried. Evaporation of the solvent gave the residue,
MgSO4), and puri¢ed by column chromatography to yield 2 (12 mg,
21
96%). ‰aŠ
7:53 (c 1.30, CHCL3). IR: 3358, 3085, 2973, 2948, 2869,
1649, 14D50, 1057, 999, 921, 899 cm
.
EIMS: m/z 155(0.2%,
1
M
15), 137(4), 109(4), 96(4), 82(22), 71(61), 67(75), 55(39), 43(100),
41(56). dH (400 MHz CDCl3): 5.90 (dd, J ˆ 17:2, 10.7 Hz, 1H,
CHˆ ), 5.22 (d, J ˆ 17:2 Hz, 1H, CHˆ) 5.06 (d, J ˆ 10:7 Hz, 1H,
CHˆ ), 4.95, 4.84 (s, 2H, CH2 ˆ), 4.06 (t, J ˆ 6:3 Hz, 1H, CHO), 2.17
(bs, 2H, 2OH), 1.71 (s, 3H, CH3), 1.76^1.54 (m, 4H, 2CH2), 1.29 (s,
3H, CH3). dC(100 MHz, CDCl3) 147.34, 145.01, 111.76, 110.83, 75.60,
72.86, 37.66, 29.10, 27.88, 17.84.
which chromatographed
petroleum±ethyl acetate (4:1 v/v) to afford epoxy alcohol
was
¯ash
eluting
with
light
7
24
D
(177 mg, 77%) as a colorless oil. ‰aŠ
6:4 (c 0.75, CHCl3). IR: 3454,
This work was ¢nancially supported by the National
Nature Science Foundation of China (Grant No. 29672015)
and the Special Research Grant for Doctoral Sites in Chinese
Universities.
3089, 2974, 2934, 1736, 1643, 1247, 1027, 927, 875 cm 1. EIMS:
m/z 197(0.2%, M 31), 153 (0.4), 137(2), 111(6), 94(20), 79(27), 71(30),
55(24), 43(100). dH (400 MHz, CDCl3): 5.91 (dd, J ˆ 17:3 10.8 Hz,
1H, CHˆ), 5.15 (d, J ˆ 17:3 Hz, 1H, CHˆ), 5.11 (d, J ˆ 10:8 Hz,
1H, CH), 3.66 (d, J ˆ 12:1 Hz, 1H, OCH), 3.54 (d, J ˆ 12:1 Hz,
OCH) 3.01 (t, J ˆ 6:4 Hz, 1H epoxy H), 2.00 (s, 3H, CH3), 2.03^1.95
(m, 1H, CH), 1.91^1.84 (m, H, CH), 1.65^1.59 (m, 1H, CH), 1.56^1.47
(m, 1H, CH), 1.55 (s, 3H, CH3), 1.30 (s, 3H, CH3).
Received, 22nd December 1998; Accepted, 28th January 1999
Paper E/8/07189F
(‡)-3,7-Dimethyl-6-hydroxy-3-acetoxyocta-1,7-diene (1).öTo a sol-
ution of epoxy alcohol
7
(140 mg, 0.61mmol) in dry
References
Et2O CH3CN (5:3, 8 mL) was added sequentially Ph3P (482 mg,
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at 0 8C. After stirring for 2 h at 0 8C, H2O (11 lL, 0.61 mmol)
was added to the system. The reaction mixture was re¯uxed for 6 h
at 38 8C, then 20% Na2S2O3 (aq) (2 mL) and saturated NaHCO3
(aq) (2 mL) were added to quench the reaction and the organic
layer extracted with ether ꢀ3 Â 50 mL). The combined ether extracts
were washed with 5% HCl ꢀ4 Â 10 mL), saturated NaHCO3
(10 mL), H2O and brine, then dried. Evaporation of the solvent
gave the residue, which was ¯ash chromatographed eluting with
1
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4
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24
D
a colorless oil.‰aŠ ‡ 6:0 (c 0.80, CHCl3). IR: 3435, 3075, 2974, 2941,
1
1736, 1647, 1251, 1020, 901cm
.
EIMS: m/z 152(0.4%,
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M
HOAc), 137(4), 109(5), 93(7), 71(58), 67(65), 55(23), 43(100).
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4.84 (s, 2H, CH2 ˆ), 4.03 (t, J ˆ 6:4 Hz 1H, CHO), 2.00 (s, 3H, CH3,
8
9
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