P. Wang et al. / Tetrahedron 71 (2015) 4647e4650
4649
4
4
. Experimental section
1.6 mmol) dropwise over a period of 10 min. Then, the solution
was stirred overnight. The solvent was evaporated under reduced
pressure and the resulting oil was purified by flash column
chromatography to give a white solid (353 mg, 72.8%). Mp
.1. General methods
ꢁ
1
Commercial reagents and solvents were used without further
118.5e120.8 C. H NMR (400 MHz, CDCl
3
): ppm 7.98 (d, J¼8.7 Hz,
purification unless otherwise mentioned. All anhydrous solvents
were prepared according to the reported procedures and distilled
under argon prior to use. All the stable compounds were charac-
2H), 6.93 (d, J¼8.7 Hz, 2H), 5.48 (t, J¼6.3 Hz, 1H), 4.58 (d, J¼6.5 Hz,
2H), 3.88 (s, 3H), 2.64 (d, J¼12.4 Hz, 1H), 2.22e2.04 (m, 2H), 1.94
(s, 3H), 1.76 (s, 3H), 1.73e1.50 (m, 6H), 1.47 (s, 3H), 1.45e1.36 (m,
1
13
terized by MS, H, and C NMR. Melting points were determined on
3H), 1.30e1.11 (m, 2H), 1.00e0.95 (m, 2H), 0.87 (s, 3H), 0.83 (s,
1
13
a digital melting point apparatus WRS-113 and uncorrected. H and
3H), 0.78 (s, 3H). C NMR (100 MHz, CDCl
3
):170.1, 166.9, 162.8,
13
C NMR spectra were determined on Bruker 400 instruments in
CDCl using tetramethylsilane as internal reference. Mass spectra
142.9, 131.6, 122.5, 118.6, 114.3, 88.1, 65.1, 58.7, 55.7, 51.9, 42.8, 42.0,
39.6, 39.5, 38.8, 33.4, 33.2, 24.6, 23.0, 21.5, 20.5, 20.1, 18.4, 16.9,
3
were recorded on a Micromass GCT CA055. Optical rotations were
measured using Rudolph Research Analytical Automatic Polarim-
eter III at ambient temperature and 589 nm. HPLC analyses were
performed on Agilent Technologies 1200 Series equipped with
a Diamonsil C18 column, using a mixture of methanol/water as
15.8; HRMS-ESI: calcd for C30
507.3081.
H
44
O
5
(MþNa)þ 507.3086, found
4.5. 13-Hydroxy-labda-8(9),14-diene (4)
ꢁ
a mobile phase at 25 C. The analytical data for the known com-
Vinyl magnesium bromide (1.0 M in THF, 97 mL, 97 mmol) was
pounds were found to match with the literature data.
added to a solution of methyl ketone 8 (8.50 g, 32.4 mmol) in THF
ꢁ
(500 mL) at 0 C and then stirred for 3 h. The reaction was
4
.2. 8
a
,13R-Diacetoxy-labda-14-ene (6)
quenched with ice water, extracted with ethyl acetate and dried
over Na SO . Evaporation of the organic solvent gave a crude
product, which was chromatographed on silica gel to give a oily
2
4
To a stirring solution of (ꢀ)-Sclareol (3.00 g, 10 mmol) and N, N-
*
*
1
dimethyl aniline (5 mL) in CH
2
Cl
2
(10 mL) was added acetyl chloride
mixture of the 13R and 13S epimeric alcohols 4 (7.70 g, 82.3%). H
NMR (400 MHz, CDCl ): ppm 5.97e5.89 (m, 1H), 5.24e5.20 (m,
ꢁ
(
4.2 mL, 60 mmol) at 0 C under argon atmosphere. The resulting
3
ꢁ
mixture was stirred at 50 C for 5 h and diluted with ethyl acetate
100 mL). The ethyl acetate solution was washed with 1.0 M HCl
until the organic layer was colorless. It was then washed with
water, brine and dried over Na SO . Evaporation of the organic
solvent gave a crude product, which was purified on silica gel to
1H), 5.08e5.05 (m, 1H), 2.10e1.77 (m, 5H), 1.70e1.57 (m, 4H),
1.57e1.32 (m, 7H), 1.29 (s, 3H), 1.19e1.08 (m, 3H), 0.93 (s, 3H), 0.88
(
13
3
(s, 3H), 0.83 (s, 3H); C NMR (100 MHz, CDCl ): 145.1 and 145.0
*
*
*
*
2
4
(13R and 13S ), 140.1 and 140.0 (13R and 13S ), 125.8, 111.9 and
*
*
111.8 (13R and 13S ), 73.7, 52.0, 42.6, 41.9, 39.2, 37.2, 33.7, 33.5,
ꢁ
1
give a white solid 6 (3.80 g, 97.0%). Mp 79.7e81.1 C. H NMR
400 MHz, CDCl
33.4, 27.7, 27.5, 22.2, 21.8, 20.2, 19.6, 19.2; HRMS-EI: calcd for
C H34O 290.2610, found 290.2613.
20
(
3
): ppm 5.97 (dd, J¼17.5, 11.0 Hz, 1H), 5.18e5.11 (m,
H), 2.63 (d, J¼12.4 Hz, 1H), 2.01 (s, 3H), 1.94 (s, 1H), 1.92e1.88 (m,
H), 1.73e1.57 (m, 4H), 1.54 (s, 3H), 1.45 (s, 3H), 1.39e1.11 (m, 6H),
.99e0.92 (m, 2H), 0.86 (s, 3H), 0.82 (s, 3H), 0.78 (s, 3H); C NMR
): 170.4, 170.0, 142.1, 113.2, 88.1, 83.4, 58.8, 55.8,
2.7, 42.0, 39.6, 39.5, 38.9, 33.5, 33.2, 23.7, 23.0, 22.4, 21.5, 20.6, 20.1,
392.2927, found
2
2
0
4.6. 13-(4-Methoxycarbonyl)phenoxy-labda-8(9),14-diene (2)
13
(
100 MHz, CDCl
3
A mixture of allyl alcohol 4 (1.50 g, 5.2 mmol), methyl 4-
4
hydroxybenzoate (1.10 g, 7.2 mmol), and n-Bu
3
P (1.50 mL,
ꢁ
19.6, 18.5, 15.9; HRMS-EI: calcd for C24
40
H O
4
6.0 mmol) was stirred in dry toluene (60 mL) at 0 C under nitrogen
atmosphere. To this mixture was added DEAD (1.3 mL, 8.2 mmol)
dropwise over period of 15 min. Then, the solution was stirred
overnight. The solvent was evaporated under reduced pressure and
3
92.2929.
.3. 8 -Acetoxy-13R-hydroxy-labda-14-ene (3b)
To a stirring solution of diacetate 6 (1.96 g, 5.1 mmol) in
4
a
the resulting oil was purified by flash column chromatography to
1
give a colorless liquid 2 (1.10 g, 73.8%). H NMR (400 MHz, CDCl
3
):
methanol (20 mL) was added potassium carbonate (0.69 g,
ppm 7.98 (d, J¼8.6 Hz, 2H), 6.93 (d, J¼8.7 Hz, 2H), 5.50 (t, J¼5.6, Hz,
1H), 4.59 (d, J¼6.5 Hz, 2H), 3.88 (s, 3H), 2.20e1.91 (m, 5H),
1.84e1.81 (m, 1H), 1.78 (s, 3H), 1.70e1.62 (m, 2H), 1.58 (s, 3H),
1.54e1.26 (m, 4H), 1.19e1.08 (m, 3H), 0.95 (s, 3H), 0.89 (s, 3H), 0.83
ꢁ
5
.1 mmol). Then, the reaction mixture was stirred at 40 C over-
night. After removal of methanol under reduced pressure, the
residue was dissolved in ethyl acetate (100 mL), washed with water
13
and dried over Na
2
SO
4
. Evaporation of the organic solvent gave
(s, 3H); C NMR (100 MHz, CDCl
3
):166.9, 162.7, 142.8, 140.0, 131.6,
a crude product, which was chromatographed on silica gel to give
126.2, 122.4, 118.2, 114.3, 65.1, 51.9, 51.8, 41.8, 40.2, 39.1, 37.0, 33.7,
ꢁ
1
a white solid 3b (1.53 g, 87.0%). Mp 97.4e100.2 C. H NMR
400 MHz, CDCl
): ppm 5.90 (dd, J¼16.6, 10.8 Hz, 1H), 5.20 (d,
J¼16.6 Hz, 1H), 5.10 (d, J¼10.8 Hz, 1H), 2.64e2.61 (m, 1H), 1.90 (s,
H), 1.77e1.47 (m, 7H), 1.45 (s, 3H), 1.42e1.31 (m, 3H), 1.29 (s, 3H),
.27e1.09 (m, 3H), 1.04e0.90 (m, 2H), 0.86 (s, 3H), 0.83 (s, 3H), 0.78
s, 3H); 13C NMR (100 MHz, CDCl
): 170.3, 145.1, 111.9, 88.4, 73.7,
9.0, 55.8, 45.5, 42.0, 39.8, 39.7, 38.9, 33.5, 33.2, 28.0, 23.1, 21.6,
0.6, 20.1, 20.0, 18.4, 15.9; HRMS-EI: calcd for C22 350.2821,
33.3, 26.7, 21.7, 20.1, 19.5, 19.1, 16.8; HRMS-EI: calcd for C28
40 3
H O
(
3
424.2977, found 424.2979.
3
1
4.7. 15-(2-Hydroxy-5-methoxycarbonyl)phenyl-labda-8(9), 13
E-diene (E-9)
(
3
5
2
Allyl ether 2 (1.07 g, 2.5 mmol) was dissolved into xylene
(50 mL), and the solution was refluxed for 5 h. Evaporation of the
xylene gave a crude product, which was chromatographed on silica
gel to give 9 (324 mg, a mixture of E/Z-isomers and the ratio was
1.8/1 determined by HPLC). Then this mixture was subjected to
preparative HPLC (using a mixture of methanol/water as a eluent)
38 3
H O
found 350.2811.
4
.4. 8
a-Acetoxy-13S-(4-methoxycarbonyl)phenoxy-labda-14-
ene (7)
1
to afford a colorless amorphous solid E-9 (207 mg, 19.3%). H NMR
A mixture of monoacetate 3b (350 mg, 1.0 mmol), methyl 4-
(400 MHz, CDCl
3
): ppm 7.83e7.80 (m, 2H), 6.84 (d, J¼8.2 Hz, 1H),
hydroxybenzoate (228 mg, 1.5 mmol), and n-Bu
.2 mmol) in anhydrous CH Cl
3
P (0.30 mL,
(20 mL) was stirred at 0 C under
6.10 (br s, 1H), 5.34 (t, J¼7.0 Hz, 1H), 3.88 (s, 3H), 3.39 (d, J¼7.1 Hz,
2H), 2.16e1.78 (m, 7H), 1.81 (s, 3H), 1.69e1.61 (m, 2H), 1.27 (s, 3H),
1.50e1.36 (m, 3H), 1.20e1.10 (m, 3H), 0.94 (s, 3H), 0.88 (s, 3H), 0.83
ꢁ
1
2
2
nitrogen atmosphere. To this mixture was added DEAD (0.25 mL,