B.-D. Zhou et al. / Tetrahedron 69 (2013) 1189e1194
1193
125 MHz)
d
15.9, 29.5, 30.6, 41.5, 103.7, 158.5, 195.0; HRMS (EI) m/z
96.4, 111.2, 132.2, 138.5; HRMS (EI) m/z calcd for C11H18O2 [M]þ
182.1307, found 182.1302.
calcd for C7H9IO [M]þ 235.9698, found 235.9704.
3.2.3. (R)-6-Methyl-2-vinylcyclohex-2-enone (6). ZnBr2 was heated
at150ꢁC invacuum forhalfanhour. Thedried ZnBr2 (3.6g,15.8 mmol,
2.2 equiv) was dissolved in distilled THF (15 mL) under argon. The
solution was cooled to ꢀ30 ꢁC, then vinylmagnesium bromide
(15.8 mL, 2.2 equiv 1.0 M in THF) was added and the reaction tem-
perature was raised to room temperature about 15 min. In other flask,
a mixture of enone 5 (1.7 g, 7.2 mmol) and tetrakis (triphenylphos-
phine) palladium (0.35 mol %) was dissolved in distilled THF (8 mL)
under argon. The mixture of Grignard solution and ZnBr2 was added
to it at room temperature. Upon completion, an aqueous saturated
NH4Cl solution was added to quench the reaction at 0 ꢁC. Ether
(40 mL) was added to the mixture, and the organic layer was washed
with an aqueous saturated NH4Cl solution (3ꢃ10 mL), brine
(3ꢃ10 mL), and then dried (Na2SO4). The crude product was purified
by flash column chromatography with acetone/petroleum ether
(1:50 v/v) to give compound 6 as a light yellow oil (0.66 g, 68%).
3.2.6. (3R,4S)-4-(Methoxymethoxy)-3-methyl-1,2,3,4-tetrahydro-
tetraphene-7,12-dione (9). A solution of 2-bromonaphthalene-1,4-
dione (0.16 g, 0.66 mmol) and diene 8 (0.10 g, 0.55 mmol) in freshly
distilled toluene (8 mL) was stirred under argon at 80 ꢁC for 12 h
followed at 100 ꢁC for 2 h. After the solvent was removed invacuo, the
crude DielseAlder adduct was dissolved in MeOH (10 mL), treated
with solid K2CO3 (0.23 g, 1.7 mmol), and stirred at 64 ꢁC for 1 h. The
solvent was removed invacuo, treated with water, and extracted with
CHCl3. The organic layer was washed with brine, dried (Na2SO4),
concentrated, and purified by flash column chromatography with
ethyl acetate/petroleum ether (1:30, v/v) to give compound 9 as
a yellow solid (74 mg, 40%). Rf¼0.53 (1:10 ethyl acetate/petroleum
ether); ½a 2D0
ꢂ
þ79.5(c 1.0, ethyl acetate); mp: 175e177 ꢁC; IR (KBr) nmax
3071, 2927, 2854,1707,1671,1588,1306,1272,1037, 717cmꢀ1;1HNMR
(CDCl3, 400 MHz)
d
1.11 (3H, d, J¼6.8 Hz, CH3),1.85e1.86 (1H, m, H-2),
1.92e1.96 (1H, m, H-2), 2.11e2.15 (1H, m, H-3), 3.31e3.38 (1H, m, H-
1), 3.42(3H, s, CH3O), 3.58e3.65(1H, m, H-1), 4.65 (1H, d, J¼3.3 Hz, H-
4), 4.75e4.83 (2H, dd, J¼6.9 and 25.6 Hz), 7.73e7.85 (3H, m),
Rf¼0.58 (1:10 ethyl acetate/petroleum ether); ½a D20
ꢂ
þ48.0 (c 1.0,
CH2Cl2); IR (KBr) nmax 2925, 2854, 1630, 1549, 588 cmꢀ1
;
1H NMR
(CDCl3, 500 MHz)
d
1.15 (3H, d, J¼6.8 Hz, CH3),1.69e1.79 (1H, m, H-5),
8.23e8.27 (3H, m); 13C NMR (CDCl3, 100 MHz)
d 15.9, 25.4, 28.0, 31.7,
2.04e2.10 (1H, m, H-5), 2.38e2.48 (3H, m, 2H-4 and H-6), 5.14 (1H, d,
J¼11.3 Hz, H-20),5.64(1H, d,J¼17.6 Hz, H-20),6.51e6.56(1H,dd, J¼11.3
and 17.7 Hz, H-10), 6.97 (1H, t, J¼4.5 Hz, H-3); 13C NMR (CDCl3,
56.0, 60.7, 95.8, 125.4, 126.7, 127.5, 131.3, 132.7, 133.6, 134.4, 134.8,
135.3, 135.4, 141.9, 144.3, 183.9, 185.7; HRMS (EI) m/z calcd for
C
21H20O4 [M]þ 336.1362, found 336.1357.
125 MHz) d 16.6, 27.0, 32.1, 43.4,117.0,130.8,133.0,145.8,151.2; HRMS
(EI) m/z calcd for C9H12O [M]þ 136.0888, found 136.0877.
3.2.7. (2R,3S)-10. Following the procedure for photooxygenation,
a solution of dione 9 (36 mg, 0.11 mmol) in ethyl acetate (10 mL) was
irradiated witha150Whalogenlamp underanatmosphereofoxygen
for 48 h. Solvent was removed in vacuo and then the residue was
purified by flash column chromatography with ethyl acetate/petro-
leum ether (1:10 v/v) to give compound 10 as a yellow solid (32 mg,
85%). Rf¼0.38 (1:3 ethyl acetate/petroleum ether); mp: 181e183 ꢁC;
3.2.4. (1S,6R)-6-Methyl-2-vinylcyclohex-2-enol (7). To an ice-cold
solution of enone 6 (0.55 g, 4.0 mmol) and CeCl3$7H2O (15 mg,
0.04 mmol) in 12 mL of MeOH solid NaBH4 (167 mg, 4.4 mmol) were
added in small portions over 10 min. After the mixture was stirred at
room temperature for 5 min, Et2O and H2O were added to it. The or-
ganic layer was separated, and the aqueous layer was extracted with
Et2O three times. The combined organic layers were washed with
brine and dried over anhydrous Na2SO4. The crude product was pu-
rified by flash column chromatography with ethyl acetate/petroleum
ether (1:30, v/v) to give compound 7 as a light yellow oil (0.35 g, 62%).
½
a 2D0
ꢂ
þ215 (c 1.0, ethyl acetate), or þ235 (c 1.0, chloroform); IR (KBr)
nmax 3072, 2927, 1777, 1706, 1675, 1640, 1591, 1324, 1281, 1031,
713 cmꢀ1 1H NMR (CDCl3, 400 MHz)
;
d
1.28 (3H, d, J¼6.7 Hz, CH3),
2.58e2.63 (1H, m), 2.71e2.77 (1H, dd, J¼9.4 and 17.4 Hz), 3.00e3.07
(1H, dd, J¼7.7 and 17.4 Hz), 3.39 (3H, s, CH3O), 4.55 (1H, d, J¼6.9 Hz),
4.61 (2H, d, J¼8.1 Hz), 7.74 (1H, d, J¼7.9 Hz), 7.79e7.83 (2H, m), 8.20
(1H, d, J¼8.3Hz), 8.26(1H, d,J¼8.6Hz), 8.39(1H, d,J¼7.9 Hz); 13CNMR
Rf¼0.39 (1:10 ethyl acetate/petroleum ether); ½a D20
þ138 (c 1.0, ethyl
ꢂ
acetate); IR (KBr) nmax 3426, 3073, 3028, 2926, 1640, 1629 cmꢀ1; 1H
NMR (CDCl3, 400 MHz)
d
1.10 (3H, d, J¼6.8 Hz, CH3),1.43e1.53 (4H, m),
(CDCl3, 100 MHz) d 17.1, 33.8, 42.0, 55.6, 75.3, 94.5, 126.9, 127.4, 129.1,
2.15e2.21 (2H, m), 4.25 (1H, s, H-1), 5.03 (1H, d, J¼10.9 Hz, H-20), 5.39
132.6, 133.8, 134.5, 134.9, 136.6, 148.2, 182.2, 198.9, 204.3; HRMS (EI)
(1H, d, J¼17.6 Hz, H-20), 5.85 (1H, t, J¼4.1 Hz, H-3) 6.27e6.34 (1H, dd,
m/z calcd for C21H18O5 [M]þ 350.1154, found 350.1153.
J¼10.9 and 17.7 Hz, H-10); 13C NMR (CDCl3,100 MHz)
d 17.4, 23.9, 26.5,
34.0, 66.3, 111.2, 132.3, 137.9, 138.2; HRMS (EI) m/z calcd for C9H14
O
3.2.8. (2R,3S)-2. A solution of trione 10 (30 mg, 0.1 mmol) in 4 mL
of alcohol was added 3 N HCl solution, then it was refluxed until
reactant disappeared (TLC monitoring). Solvent was removed in
vacuo and then residue was purified by flash column chromatog-
raphy to afford compound 2 as a yellow solid (23 mg, 88%). Rf¼0.10
(1:3 ethyl acetate/petroleum ether). Its purity was checked by HPLC
[M]þ 138.1045, found 138.1041.
3.2.5. (5R,6S)-6-(Methoxymethoxy)-5-methyl-1-vinylcyclohex-1-ene
(8). To a solution of the enol 7 (0.33 g, 2.4 mmol) and a catalytic
amount of DMAP in 10 mL of CH2Cl2, were added 0.83 mL
(4.8 mmol) of DIPEA and 0.55 mL (7.2 mmol) of MOMCl. The mix-
ture was stirred at room temperature for 4 h. A cold aqueous sat-
urated NaHCO3 solution was added to quench the reaction. Then, it
was diluted with Et2O and H2O. The organic layer was separated,
and the aqueous layer was extracted with Et2O three times. The
combined organic layers were washed with brine and dried over
anhydrous Na2SO4. The crude product was purified by flash column
chromatography with ethyl acetate/petroleum ether (1:50, v/v) to
give compound 8 as a light yellow oil (0.33 g, 77%). Rf¼0.55 (1:30
as 98%. Mp: 172e174 ꢁC; ½a D20
þ75.3 (c 0.5, chloroform); IR (KBr)
ꢂ
nmax 3678, 3440, 3073, 2925, 1699, 1673, 1640, 1591, 1326, 1285,
714 cmꢀ1; 1H NMR (CDCl3, 400 MHz)
d
1.23 (3H, d, J¼6.9 Hz, CH3),
2.13 (1H, d, J¼3.0 Hz, OH), 2.55e2.63 (1H, m), 2.79e2.85 (1H, dd,
J¼8.6 and 16.8 Hz), 2.94e3.00 (1H, dd, J¼6.8 and 16.8 Hz), 4.83 (1H,
s), 7.77 (1H, d, J¼8.1 Hz), 7.79e7.81 (2H, m), 8.18 (1H, d, J¼6.8 Hz),
8.25 (1H, d, J¼8.8 Hz), 8.39 (1H, d, J¼8.0 Hz); 13C NMR (CDCl3,
100 MHz)
d 16.6, 35.1, 42.5, 71.8, 127.2, 127.6, 130.2, 132.0, 132.7,
134.1, 134.8, 135.1, 135.2, 135.6, 135.9, 150.1, 182.5, 183.7, 198.8;
ethyl acetate/petroleum ether); ½a D20
ꢂ
þ94.3 (c 1.0, ethyl acetate); IR
HRMS (EI) m/z calcd for C19H14O4 [M]þ 306.0892, found 306.0894.
(KBr) nmax 2925, 1639, 1629, 1037 cmꢀ1; 1H NMR (CDCl3, 400 MHz)
d
1.08 (3H, d, J¼6.1 Hz, CH3), 1.26e1.69 (3H, m), 2.18e2.31 (2H, m),
3.36 (3H, s, CH3O), 4.21 (1H, s, H-6), 4.70e4.76 (2H, dd, J¼6.8 and
17.5 Hz), 4.99 (1H, d, J¼11.1 Hz, H-20), 5.44 (1H, d, J¼17.6 Hz, H-20),
5.91 (1H, t, J¼3.8 Hz, H-2), 6.31e6.38 (1H, dd, J¼11.1 and 17.6 Hz, H-
Acknowledgements
H.J.Z. thanks the financial support from NSFC (30873141), 973
Program (2009CB522300), and Hebei University. The Super-
10); 13C NMR (CDCl3, 100 MHz)
d
18.2, 24.2, 26.1, 34.0, 55.6, 71.8,