Synthesis of (±)-Bakuchiol via a Pot-Economy Approach
Preparation of (E)-2-(3,7-dimethylocta-2,6-dien-1-
warmed up to −30 ℃ and stirred for 40h. After con-
centrated under reduced pressure, the residue was sub-
jected to purification on silica gel chromatography
(PE/EtOAc: 300/1) to provide 2 (dr=9.2∶1) as color-
less oil (1.20 g, 71% yield).
[
25]
yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3b)
To a solution of geraniol (1.54 g, 10.0 mmol) in
DMSO/MeOH (30.0 mL/30.0 mL) was added di-μ-
chlorobis[2-[(dimethylamino)methyl]phenyl-C,N]dipal-
ladium(II) (138 mg, 0.25 mmol), TsOH (86.0 mg, 0.50
[8-11,14]
Synthesis of rac-bakuchiol (1)
mmol) and (pinB)
perature under nitrogen. The mixture was warmed up to
0 ℃ and stirred for 7 h. After concentrated under re-
duced pressure, the residue was diluted with EtOAc (50
mL). The organic phase was washed with H O (30 mL
3) to remove the DMSO. The combined organic lay-
ers were washed with brine, dried over anhydrous
Na SO , filtered, and concentrated under reduced pres-
2
(2.60 g, 10.2 mmol) at room tem-
To a solution of 2 (200 mg, 0.52 mmol) in pyridine
(
0
3.10 mL, 38.6 mmol) was added MeSO
.57 mmol) at 0 ℃ under nitrogen. The mixture was
warmed up to room temperature and stirred for 10 h.
Then the reaction mixture was quenched with H O (2
2
Cl (44.0 μL,
5
2
×
2
mL). The aqueous phase was extracted with EtOAc (10
mL). The combined organic layers were washed with
H O (5 mL×2), dried over anhydrous Mg SO , filtered,
2 2 4
and concentrated under reduced pressure. Without fur-
ther purification, the residue was dissolved in DMSO
2
4
sure. The residue was subjected to purification on silica
gel chromatography (PE/EtOAc: 10/1) to provide 3b as
1
pale yellow oil (2.30 g, 87% yield). H NMR (400 MHz,
(
(
1.60 mL) under nitrogen. After addition of t-BuOK
1.0 mL, 1.0 mol•L in THF, 1.0 mmol) to the solution
CDCl
3
) δ: 5.25 (t, J=7.2 Hz, 1H), 5.10 (t, J=6.0 Hz,
-
1
1
-
H), 1.95-2.08 (m, 4H), 1.68 (s, 3H), 1.60 (s, 6H) 1.26
1.28 (m, 2H), 1.24 (s, 12H). ESI-MS m/z: 264.2.
at room temperature under nitrogen, the reaction mix-
ture was warmed up to 80 ℃ and stirred for 2.5 h.
Then the mixture was cooled to room temperature and
Preparation of 1-(4-((tert-butyldimethylsilyl)oxy)phe-
nyl)-3,7-dimethyl-3-vinyloct-6-en-2-ol (2)
2
poured into H O (5 mL). The aqueous phase was ex-
Method A: To a solution of 9-BBN (7.50 mL, 0.5
tracted with EtOAc (5 mL×2). The combined organic
layers were washed with brine, dried over anhydrous
Mg SO , filtered, and concentrated under reduced pres-
2 4
-
1
mol•L in THF, 3.74 mmol) was dropwise added a
solution of allene 5 (425 mg, 3.12 mmol) in THF (15.0
mL) at −78 ℃ under nitrogen. After being stirred at
sure. The residue was subjected to purification on silica
gel chromatography (PE/EtOAc: 10/1) to provide 1 as
colorless oil (58 mg, 44% yield). Racemic, determined
−
78 ℃ for 15 min, the mixture was allowed to stir at
room temperature for 5 h. Then the mixture was again
cooled to −78 ℃ and slowly added aldehyde 4. After
the addition was complete, the reaction mixture was
stirred at −78 ℃ for 15 min and then warmed up to
room temperature. Stirring was continued for 10 h at
room temperature monitored by TLC. The reaction
mixture was added triethanolamine and then concen-
trated under reduced pressure. The residue was sub-
jected to purification on silica gel chromatography
i
by HPLC (OJ-H, PrOH/n-Hexane=1/99, flow rate=
0.7 mL/min, T=25 ℃, λ=214 nm): tR1=30.91 min,
1
t
R2(minor)=37.53 min; H NMR (400 MHz, CDCl
3
) δ:
7
(
.25 (d, J=8.8 Hz, 2H), 6.76 (d, J=8.4 Hz, 2H), 6.25
d, J=16.4 Hz, 1H), 6.05 (d, J=16.4 Hz, 1H), 5.88 (dd,
=17.2 Hz, J =10.8 Hz, 1H), 4.97-5.15 (m, 3H),
.69 (s, 1H), 1.90-2.00 (m, 2H), 1.67 (s, 3H), 1.58 (s,
J
1
2
4
3
13
H), 1.46-1.52 (m, 2H), 1.19 (s, 3H); C NMR (100
) δ: 154.66, 146.01, 135.96, 131.27, 131.02,
27.39, 126.53, 124.86, 115.38, 111.86, 42.53, 41.33,
5.66, 23.43, 23.25, 17.62; IR (KBr) ν: 3385, 2961,
MHz, CDCl
3
(
PE/EtOAc: 300/1) to provide 2 (dr=2∶1) as colorless
1
2
2
oil (541 mg, 56% yield). Diastereomeric excess: 33%,
i
determined by HPLC (IC-H, PrOH/n-Hexane=1/99,
−1
925, 1610, 1513 cm ; HRMS (EI) m/z calculated for
flow rate=0.5 mL/min, T=25 ℃, λ=214 nm): t =
R1
+
18
C H24O [M] 256.1827, found 256.1823.
8
.13 min, tR2(minor)=9.27 min, tR3(minor)=10.50 min;
1
H NMR (400 MHz, CDCl
3
) δ: 7.03-7.10 (m, 2H),
6
5
1
1
1
.77 (d, J=8.0 Hz, 2H), 5.79-5.91 (m, 1H), 5.04-
Acknowledgement
.24 (m, 3H), 3.50 (d, J=10.0 Hz, 1H), 2.82 (d, J=
4.0 Hz, 1H), 2.34-2.45 (m, 1H), 1.85-2.00 (m, 2H),
.68 (s, 3H), 1.60 (s, 3H), 1.43-1.51 (m, 2H), 1.07-
We thank the National Natural Science Foundation
of China (21272147 to X. Jia) and Chinese Academy of
Sciences (to R. Hong) for financial support.
13
.20 (m, 3H), 0.97 (s, 9H), 0.18 (s, 6H); C NMR (100
) δ: 154.1, 143.8, 143.7, 132.3, 132.2,
30.2, 130.1, 124.9, 124.8, 120.9, 120.5, 114.6, 114.2,
MHz, CDCl
3
References
1
7
2
2
8.8, 78.3, 44.6, 44.4, 37.7, 37.6, 37.4, 37.1, 25.7, 22.8,
[1] Khushboo, P. S.; Jadhav, V. M.; Kadam, V. J.; Sathe, N. S.
2.7, 18.2, 17.6, 17.5, −4.4; IR (KBr) ν: 3586, 2958,
Pharmacogn. Rev. 2010, 4, 69.
−1
[
2] Mehta, G.; Nayak, U. R.; Dev, S. Tetrahedron Lett. 1966, 7, 4561.
[3] Labbe, C.; Faini, F.; Coll, J.; Connolly, J. D. Phytochemistry 1996,
2, 1299.
930, 1609, 1509, 1259, 916 cm ; HRMS (EI) m/z cal-
+
culated for C24
88.2797.
Method B: To a solution of 3b (1.15 g, 4.35 mmol)
H
40
O
2
Si [M]
388.2798, found
4
3
[
4] Wu, C. Z.; Cai, X. F.; Dat, N. T.; Hong, S. S.; Han, A. R.; Seo, E. K.;
Hwang, B. Y.; Nan, J. X.; Lee, D.; Lee, J. J. Tetrahedron Lett. 2007,
48, 8861.
in THF (44.0 mL) was added aldehyde 4 (1.10 g, 4.35
mmol) at −78 ℃ under nitrogen. The mixture was
[5] Wu, C. Z.; Hong, S. S.; Cai, X. F.; Dat, N. T.; Nan, J. X.; Hwang, B.
Chin. J. Chem. 2014, XX, 1—X
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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