Wang et al.
FULL PAPER
36 mmol) and KI (29.4 g, 180 mmol) in water (100 mL)
portionwise at room temperature. After the addition, the
mixture was stirred overnight at the same temperature.
Then, hydrochloric acid (2.0 mol/L) was added in to
adjust the pH of the mixture to pH=2.0 and white solid
material precipitated. After filtration, the filtercake was
washed with water. The white solid material was dried
and then dissolved in DMF (100 mL). Then, K2CO3
(20.0 g, 72 mmol) was added to the mixture, and it was
stirred for 1 h at room temperature before MeI (10.0 mL,
144 mmol) was added, and stirring was continued over-
night. The mixture was diluted with water and extracted
with ethyl acetate (120 mL×2). The organic layer was
washed with water and then dried with anhydrous so-
dium sulfate. After the concentration under vacuum, the
crude product was purified by column chromatography
to give compound 1 (8.4 g, 79%) as white solid. m.p.
94.7-95.2 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.45 (d,
J=2.0 Hz, 1H), 8.01 (dd, J=8.4, 2.0 Hz, 1H), 6.83 (d,
J=8.8 Hz, 1H), 3.94 (s, 3H), 3.89 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 165.1, 161.2, 140.1, 131.2, 123.9,
109.5, 84.9, 56.1, 51.7; HRMS (EI) calcd for C9H9O3I
291.9596, found 291.9594.
4-((1R,2R,8aS)-2-Hydroxy-2,5,5,8a-tetramethyl-
decahydronaphthalen-1-yl)butan-2-one (5)[5] To a
stirred solution of (−)-Sclareol (30.8 g, 0.1 mol) in ace-
tone (500 mL) was added a mixture of KMnO4 (55.3 g,
0.35 mol) and MgSO4 (60.2 g, 0.5 mol) portionwise at 0
℃. After the addition, the mixture was stirred overnight
at room temperature. The solid material was removed by
filtration. The filtrate was concentrated under reduced
pressure to give compound 5 (25.8 g) which was used
for the next step without further purification.
in THF (500 mL) was added dropwise vinyl magnesium
bromide (97.0 mL, 97 mmol, 1.0 mol/L in THF) at 0 ℃.
After the addition, the mixture was stirred at room tem-
perature for another 3 h. Then, water was added to
quench the reaction. THF was removed under reduced
pressure and the residue was diluted with ethyl acetate.
The organic layer was washed with brine and dried over
anhydrous sodium sulfate. After filtration and concen-
tration, the crude product was purified by column
chromatography to give compound 7 (7.7 g, 82.3%) as
1
yellow oil. H NMR (400 MHz, CDCl3) δ: 5.89-5.97
(m, 1H), 5.20-5.24 (m, 1H), 5.05-5.08 (m, 1H), 1.77
-2.10 (m, 5H), 1.57-1.70 (m, 4H), 1.32-1.57 (m,
7H), 1.29 (s, 3H), 1.08-1.19 (m, 3H), 0.93 (s, 3H),
0.88 (s, 3H), 0.83 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ: 145.1, 145.0, 140.1, 140.0, 125.8, 111.9, 111.8, 73.7,
52.0, 42.6, 41.9, 39.2, 37.2, 33.7, 33.5, 33.4, 27.7, 27.5,
22.2, 21.8, 20.2, 19.6, 19.2; HRMS (EI) calcd for
C20H34O 290.2610, found 290.2613.
3-Methyl-5-((8aS)-2,5,5,8a-tetramethyl-3,4,4a,5,6,
7,8,8a-octahydronaphthalen-1-yl)pent-1-en-3-yl ace-
tate (3) To the stirred solution of compound 7 (480
mg, 1.7 mmol) in N,N-dimethyl aniline (5 mL) and
DCM (10 mL) was added dropwise acetyl chloride (0.7
mL, 10 mmol) at 0 ℃. Then, the mixture was heated to
50 ℃ and stirred overnight. Ethyl acetate was added to
dilute the mixture after the starting material was con-
sumed. The mixture was washed with hydrochloric acid
(1.0 mol/L) until it turned to colorless. The organic layer
was washed with brine and dried over anhydrous so-
dium sulfate. After filtration and concentration, the
crude product was purified by column chromatography
to give compound 3 (494 mg, 90%) as white solid.
1
4-((8aS)-2,5,5,8a-Tetramethyl-3,4,4a,5,6,7,8,8a-
octahydronaphthalen-1-yl)butan-2-one (6)[5] To a
stirred solution of compound 5 (28.0 g, 0.1 mol) in tolu-
ene (2.0 L) was added iodine (1.3 g, 5.0 mmol). Then,
the mixture was heated to 150 ℃ with Dean-Stark
equipment for 3 h. Upon cooling, aqueous Na2S2O3 was
added to quench the reaction. The mixture was extracted
with ethyl acetate. The organic layer was washed with
brine and dried over anhydrous sodium sulfate. After
filtration and concentration, the crude product was puri-
fied by column chromatography to give compound 6
(23.6 g, 82% over two steps) as a yellow oil. [α]D25
+74.5 (c 1.05, CHCl3); 1H NMR (400 MHz, CDCl3) δ:
2.49 (t, J=8.4 Hz, 2H), 2.25-2.33 (m, 1H), 2.16-
2.19 (m, 1H), 2.14 (s, 3H), 1.91-2.02 (m, 2H), 1.78 (br,
J=12.4 Hz, 1H), 1.63-1.66 (m, 1H), 1.58-1.61 (m,
1H), 1.53 (s, 3H), 1.47-1.48 (m, 1H), 1.42-1.45 (m,
1H), 1.37-1.40 (m, 1H), 1.12-1.17 (m, 1H), 1.09 (d,
J=11.6 Hz, 1H), 0.96-1.05 (m, 1H), 0.88 (s, 3H), 0.94
(s, 3H), 0.83 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
209.1, 139.2, 126.6, 52.0, 44.6, 41.7, 39.1, 36.9, 33.6,
33.3, 29.8, 21.7, 21.6, 19.9, 19.4, 19.0.
[α]24 +57.0 (c 1.12, CHCl3); H NMR (400 MHz,
D
CDCl3) δ: 5.99 (dd, J=17.0, 11.5 Hz, 1H), 5.15-5.20
(m, 2H), 2.65 (d, J=12.0 Hz, 1H), 2.05 (s, 3H), 1.69-
2.12 (m, 5H), 1.55-1.68 (m, 4H), 1.31-1.54 (m, 6H),
1.30 (s, 3H), 1.07-1.20 (m, 3H), 0.93 (s, 3H), 0.89 (s,
3H), 0.82 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 169.9,
111.8 (111.7), 139.7 (139.6), 126.2, 113.1, 83.2 (83.1),
51.9, 41.8, 40.3, 39.1, 37.0, 33.7, 33.3, 23.3, 23.2, 22.2,
21.7, 20.2, 19.4, 19.1; HRMS (EI) calcd for C22H36O2
332.2715, found 332.2717.
Methyl 4-methoxy-3-(3-methyl-5-((4aS,8aS)-2,5,5,
8a-tetramethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalen-
1-yl)pent-2-enyl)benzoate (8) To a solution of com-
pound 3 (50 mg, 0.15 mmol) and compound 1 (60 mg,
0.2 mmol) in DMF (5.0 mL) in a sealed tube was added
TBAC (63 mg, 0.23 mmol), Pd(OAc)2 and triethylamine
(0.2 mL, 1.2 mmol). Then, the mixture was sealed up
and heated to 120 ℃ for 12 h. Upon cooling, the mix-
ture was filtered to remove the solid material. The fil-
trate was washed with water and dried over anhydrous
sodium sulfate. After filtration and concentration, the
crude product was purified by column chromatography
to give compound 8 (23 mg, mixture of E∶Z=1∶1
3-Methyl-5-((8aS)-2,5,5,8a-tetramethyl-3,4,4a,5,6,
7,8,8a-octahydronaphthalen-1-yl)pent-1-en-3-ol (7)
To a stirred solution of compound 6 (8.5 g, 32.4 mmol)
36.2%, [α]25 +22.0 (c 1.31, CHCl3)) as a colorless oil
D
in which small amount of sample was separated by
680
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2015, 33, 679—682