The Journal of Organic Chemistry
Article
give 2a1-hydroxy-4,4,12a-trimethyl-11-(3-methylbut-2-en-1-yl)-
3,3a,4,11,12,12a-hexahydro-1H-2a,11 methanocyclopenta[3,4]indeno-
[1,7a-b]naphthalene-9,10,13(2H,2a1H)-trione 19 (50 mg, 25%) as a
white crystalline solid. Data for 19: Rf 0.42 (petrol/EtOAc, 4:1); mp
204−206 °C; IR (neat) 3468, 2949, 1736, 1707, 1663, 1599, 1118, 765
2913, 1647, 1439, 1375, 1187, 893 cm−1; 1H NMR (600 MHz,
CDCl3) δ 5.03 (tt, J = 7.9, 1.3 Hz, 1H), 4.91−4.89 (m, 1H), 4.75 (s,
1H), 3.28 (dd, J = 9.8, 5.8 Hz, 1H), 3.19 (dd, J = 9.8, 7.7 Hz, 1H), 2.29
(dt, J = 14.3, 7.1, 1H), 2.24 (dt, J = 14.3, 7.1 Hz, 1H), 2.11 (dt, J =
14.3, 7.0 Hz, 1H), 1.69 (s, 3H), 1.68 (s, 3H), 1.63 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 145.5, 133.4, 121.5, 112.8, 49.4, 39.9, 25.8, 19.3,
18.0, 11.3.
1
cm−1; H NMR (600 MHz, CDCl3) δ 7.70 (dd, J = 7.6, 1.3 Hz 1H),
7.54 (td, J = 7.6, 1.3 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.35 (d, J = 7.6
Hz, 1H), 5.05 (t, J = 7.2 Hz, 1H), 2.85 (s, 1H), 2.68 (dd, J = 9.8, 7.7
Hz, 1H), 2.37 (t, J = 12.1 Hz, 1H), 2.28 (d, J = 7.3 Hz, 2H), 2.26−2.23
(m, 1H), 2.06 (dd, J = 11.5, 7.7 Hz, 1H), 1.98−1.93 (m, 1H), 1.82−
1.71 (m, 2H), 1.78 (d, J = 13.9 Hz, 1H), 1.68 (d, J = 13.9 Hz, 1H),
1.65 (s, 3H), 1.57 (s, 3H), 1.49 (s, 3H), 1.36 (s, 3H), 1.11 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 213.4, 203.4, 200.2, 150.3, 136.3, 134.3,
133.7, 126.9, 126.4, 123.5, 118.8, 90.9, 72.8, 68.5, 63.1, 57.0, 46.0, 44.7,
39.5, 37.2, 29.9, 29.0, 26.2, 25.9, 25.1, 24.5, 22.9, 17.9; HRMS-ESI (m/
z) calculated for C28H33O4 [M + H]+ 433.2373, found 433.2372.
( )-Ethyl 5-methyl-2-(prop-1-en-2-yl)hex-4-enoate (( )-21).
To a solution of LDA (2.0 M in heptane, 46.8 mL, 93.6 mmol) and
anhydrous THF (80 mL) was added ethyl 3,3-dimethyl acrylate 20
(10.0 g, 78 mmol) in anhydrous THF (12 mL) dropwise at −78 °C.
The mixture was stirred at −78 °C for 15 min. Prenyl bromide (9.90
mL, 85.8 mmol) was then added at −78 °C. The reaction mixture was
stirred for a further 1 h before gradual warming to rt. The mixture was
quenched with satd NH4Cl solution (100 mL) and extracted with
Et2O (3 × 100 mL). The combined organics were washed with brine
(200 mL), dried over anhydrous MgSO4, filtered, and concentrated in
vacuo. The residue was purified by flash chromatography on SiO2
(petrol/EtOAc, 20:1 as elutant) to give ( )-ethyl 5-methyl-2-(prop-1-
en-2-yl)hex-4-enoate ( )-21 (13.3 g, 87%) as a colorless oil. Data for
( )-21: Rf 0.65 (petrol/EtOAc, 4:1); IR (neat) 2976, 1733, 1647,
1179, 1150, 895 cm−1; 1H NMR (600 MHz, CDCl3) δ 5.03 (t, J = 7.1
Hz, 1H), 4.91−4.86 (m, 2H), 4.13 (qd, J = 7.1, 1.8 Hz, 2H), 3.01 (t, J
= 7.7 Hz, 1H), 2.51 (dt, J = 15.1, 7.8 Hz, 1H), 2.26 (dt, J = 14.3, 7.0
Hz, 1H), 1.76 (s, 3H), 1.68 (s, 3H), 1.62 (d, J = 11.5 Hz, 3H), 1.24 (t,
J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.5, 142.5, 133.4,
121.2, 113.4, 60.4, 53.3, 29.0, 25.7, 20.5, 17.8, 14.2.
(
)-2-Benzoyl-3,5-dihydroxy-6-(5-methyl-2-(prop-1-en-2-
yl)hex-4-en-1-yl)-4,6-bis(3-methylbut-2-en-1-yl)cyclohexa-2,4-
dienone (( )-24). To a solution of 17 (616 mg, 1.68 mmol) in
anhydrous DMF (12 mL) was added NaH (242 mg, 10.1 mmol) at rt.
The mixture was stirred at rt for 10 min. Iodide ( )-23 (2.66 g, 10.1
mmol) in anhydrous DMF (2 mL) was then added at rt. The reaction
mixture was stirred at rt for 1 h. The mixture was quenched with 1 M
HCl solution (15 mL) and extracted with EtOAc (3 × 20 mL). The
combined organics were washed sequentially with H2O (2 × 30 mL)
and brine (30 mL), dried over anhydrous MgSO4, filtered, and
concentrated in vacuo. The residue was purified by flash chromatog-
raphy on SiO2 (petrol/EtOAc, 50:1 → 15:1 gradient elution) to give
( )-2-benzoyl-3,5-dihydroxy-6-(5-methyl-2-(prop-1-en-2-yl)hex-4-en-
1-yl)-4,6-bis(3-methylbut-2-en-1-yl)cyclohexa-2,4-dienone ( )-24
(242 mg, 29%, 50% BRSM) as a viscous yellow oil. Data for
( )-24: Rf 0.42 (petrol/EtOAc, 4:1); IR (neat) 3278, 2914, 1645,
1445, 1182, 695 cm−1; NMR showed a complex mixture of tautomers
and diasteroisomers; HRMS-ESI (m/z) calculated for C33H43O4 [M +
H]+ 503.3156, found 503.3149.
( )-Garcibracteatone (1) and ( )-5-epi-Garcibracteatone
(25). To a solution of Mn(OAc)3(H2O)2 (457 mg, 1.70 mmol) and
Cu(OAc)2(H2O) (154 mg, 0.85 mmol) in degassed AcOH (2 mL)
was added ( )-24 (408 mg, 0.81 mmol) in degassed AcOH (12 mL)
at rt. The reaction mixture was stirred at rt for 3 h. The mixture was
quenched with H2O (20 mL) and extracted with EtOAc (3 × 30 mL).
The combined organics were washed sequentially with H2O (50 mL),
sat. NaHCO3 solution (50 mL), and brine (50 mL), dried over
anhydrous MgSO4, filtered, and concentrated in vacuo. The residue
was purified by flash chromatography on SiO2 (petrol/EtOAc, 20:1 →
15:1 gradient elution) to give ( )-garcibracteatone ( )-1 (56 mg,
14%) as a white crystalline solid. Data for ( )-1: Rf 0.62 (petrol/
EtOAc, 4:1); mp 196−199 °C; IR (neat) cm−1 3468, 2977, 1736,
1706, 1665, 1601, 1450, 1260, 1111, 765; 1H NMR (600 MHz,
CDCl3) δ 7.69 (dd, J = 7.6, 1.3 Hz, 1H), 7.54 (td, J = 7.6, 1.4 Hz, 1H),
7.36 (t, J = 7.6 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H), 5.04 (t, J = 7.2 Hz,
1H), 5.01 (t, J = 7.2 Hz, 1H), 2.83 (s, 1H), 2.66 (dd, J = 9.9, 7.8 Hz,
1H), 2.30−2.23 (m, 1H), 2.27 (d, J = 7.3 Hz, 1H), 2.20 (dd, J = 11.3,
10.1 Hz, 1H), 2.12−2.05 (m, 1H), 2.07 (dd, J = 11.5, 7.8 Hz, 1H),
2.01 (dd, J = 11.8, 7.9 Hz, 1H), 1.89−1.82 (m, 1H), 1.77 (d, J = 13.9
Hz, 1H), 1.68 (d, J = 13.8 Hz, 1H), 1.68 (s, 3H), 1.65 (s, 3H), 1.62 (s,
3H), 1.59−1.55 (m, 1H), 1.57 (s, 3H), 1.55 (s, 1H), 1.46 (s, 3H), 1.35
(s, 3H), 1.10 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 213.3, 203.3,
200.3, 150.2, 136.4, 134.3, 133.6, 132.4, 126.9, 126.4, 123.5, 122.9,
118.8, 91.8, 70.2, 69.2, 63.2, 56.9, 56.8, 47.5, 41.5, 37.1, 33.0, 32.5,
29.8, 29.0, 26.2, 25.9, 25.8, 25.1, 18.4, 18.0, 17.9; HRMS-ESI (m/z)
calculated for C33H41O4 [M + H]+ 501.2999, found 501.3002. Further
elution gave ( )-5-epi-garcibracteatone ( )-25 (31 mg, 8%) as a
white crystalline solid. Data for 25: Rf 0.58 (petrol/EtOAc, 4:1); mp
212−216 °C; IR (neat) 3487, 2964, 1735, 1706, 1666, 1598, 1455,
( )-5-Methyl-2-(prop-1-en-2-yl)hex-4-en-1-ol (( )-22). To a
solution of LiAlH4 (5.60 g, 148 mmol) in Et2O (200 mL) was added
21 (13.2 g, 67.5 mmol) in Et2O (60 mL) dropwise over 20 min at 0
°C. The reaction mixture was warmed to rt and stirred for 1 h. The
mixture was then cooled to 0 °C, quenched by careful dropwise
addition of H2O (5.6 mL), and stirred at rt for 5 min. Then 15%
NaOH solution (5.6 mL) was added, and the mixture was stirred at rt
for a further 5 min before H2O (16.8 mL) was added. The mixture was
filtered and extracted thoroughly with Et2O, and the filtrate was
concentrated in vacuo to yield ( )-5-methyl-2-(prop-1-en-2-yl)hex-4-
en-1-ol ( )-22 (9.90 g, 95%) as a colorless oil which was used in the
next step without further purification. Data for ( )-22: Rf 0.39
(petrol/EtOAc, 4:1); IR (neat) 3351, 2916, 1646, 1440, 1376, 1038,
1
888 cm−1; H NMR (600 MHz, CDCl3) δ 5.08 (tt, J = 7.2, 1.2 Hz,
1H), 4.94−4.91 (m, 1H), 4.82 (d, J = 0.6 Hz, 1H), 3.57 (dt, J = 11.3,
5.8 Hz, 1H), 3.50 (dt, J = 8.7, 3 Hz, 1H) 2.28 (qd, J = 7.6, 5.2 Hz, 1H),
2.11 (dt, J = 14.6, 7.3 Hz, 1H), 2.04 (dt, J = 14.6, 7.1 Hz, 1H), 1.70 (s,
3H), 1.69 (s, 3H), 1.61 (s, 3H), 1.43 (t, J = 5.3 Hz, 1H); 13C NMR
(150 MHz, CDCl3) δ 145.4, 132.7, 122.0, 113.1, 63.6, 49.9, 28.4, 25.7,
19.5, 17.8.
1298, 1107, 760 cm−1; H NMR (600 MHz, CDCl3) δ 7.70 (dd, J =
1
(
)-3-(Iodomethyl)-2,6-dimethylhepta-1,5-diene (( )-23).
7.6, 1.2 Hz, 1H), 7.54 (td, J = 7.6, 1.4 Hz, 1H), 7.36 (t, J = 7.6 Hz,
1H), 7.35 (d, J = 7.8 Hz, 1H), 5.11 (t, J = 7.3 Hz, 1H), 5.02 (t, J = 6.9
Hz, 1H), 2.81 (s, 1H), 2.62 (dd, J = 9.8, 7.7 Hz, 1H), 2.53−2.47 (m,
1H), 2.33−2.26 (m, 1H), 2.29 (d, J = 8.0 Hz, 1H), 2.20 (dd, J = 11.2,
10.1 Hz, 1H), 2.12 (dd, J = 12.3, 10.9 Hz, 1H), 2.05 (t, J = 9.5 Hz,
1H), 2.03 (d, J = 14.2 Hz, 1H), 1.93−1.87 (m, 1H), 1.72−1.65 (m,
1H), 1.69 (s, 3H), 1.66 (s, 3H), 1.58 (s, 3H), 1.58 (s, 3H), 1.47 (s,
3H), 1.43 (d, J = 14.5 Hz, 1H), 1.38−1.34 (m, 1H), 1.35 (s, 3H), 1.10
(s, 3H); 13C NMR (150 MHz, CDCl3) δ 213.4, 203.3, 200.2, 150.2,
136.3, 134.6, 133.7, 132.6, 126.9, 126.4, 123.5, 122.8, 119.0, 91.8, 71.0,
69.1, 63.0, 56.2, 52.5, 42.5, 37.2, 35.1, 31.1, 30.2, 29.8, 29.5, 26.2, 25.9,
25.8, 24.8, 22.8, 17.9, 17.8; HRMS-ESI (m/z) calculated for C33H41O4
[M + H]+ 501.2999, found 501.3018.
To a solution of PPh3 (18.5 g, 70.6 mmol) and imidazole (4.80 g,
70.6 mmol) in CH2Cl2 (200 mL) was added I2 (17.9 g, 70.6 mmol) at
0 °C. The mixture was stirred at 0 °C for 15 min. Then 22 (9.90 mL,
64.2 mmol) in CH2Cl2 (30 mL) was added dropwise at 0 °C. The
reaction mixture was stirred at rt for 2 h. The mixture was quenched
with Na2S2O3 solution (36 g in 200 mL of H2O) and stirred at rt for
10 min. The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (200 mL). The combined organics were
washed with brine (200 mL), dried over anhydrous MgSO4, filtered,
and concentrated in vacuo. The residue was purified by flash
chromatography on SiO2 (neat petrol as elutant) to give ( )-3-
(iodomethyl)-2,6-dimethylhepta-1,5-diene ( )-23 (14,6 g, 86%) as a
pale orange oil. Data for ( )-23: Rf 0.70 (neat petrol); IR (neat) 2968,
2570
dx.doi.org/10.1021/jo500027k | J. Org. Chem. 2014, 79, 2564−2573