Full Papers
1
3
H), 2.54–2.34 (m, 3H), 2.15 (m, 1H), 1.91–1.81 (m, 1H), 1.77 (s,
H), 1.72 (m, 1H), 1.65 (s, 3H), 1.63 (s, 3H), 1.57 (s, 3H), 1.34 ppm
added to the residue and the mixture was heated at 1358C and
stirred overnight. The mixture was cooled, quenched with 1m HCl
and then extracted with EtOAc (ꢃ3). The combined organics were
1
3
(
s, 1H); C NMR (125 MHz, CDCl ): d=200.3, 187.6, 165.2, 164.0,
3
1
5
1
1
51.7, 131.8, 131.8, 124.1, 123.9, 114.8, 100.1, 97.3, 89.4, 61.4, 59.3,
6.4, 55.8, 44.2, 38.5, 32.6, 30.2, 25.8, 23.0, 21.3, 21.0, 18.1,
7.8 ppm; IR (neat): n˜ =2922, 1767, 1678, 1594, 1563, 1332,
washed with brine (ꢃ3), dried over anhydrous MgSO , filtered and
concentrated in vacuo. The residue was purified by flash chroma-
tography on SiO2.
4
ꢀ
1
203 cm ; HRMS (ESI): calculated for C H O BrNa 523.1460 [M+
27
33
4
+
Method B: Dimethylated compound (1 equiv) and LiCl (15 equiv)
were dissolved in DMF (0.1m) and then heated at 1508C under mi-
crowave irradiation and stirred for 4 h. The mixture was cooled and
quenched with 1m HCl and then extracted with EtOAc (ꢃ3). The
combined organics were washed with brine (ꢃ3), dried over anhy-
Na] , found 523.1451.
(
ꢁ)-(3aS,4S,5S,10bS)-7,9-Dimethoxy-4,5-dimethyl-4-(4-methyl-
pent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-
,10b-methanobenzo[e]azulene-6,11-dione (12d): 11 d (300 mg,
.684 mmol), CHCl (30 mL), Pb(OAc) (334 mg, 0.752 mmol). Chro-
5
0
drous MgSO , filtered and concentrated in vacuo. The residue was
3
4
4
matographic eluent: (petrol/ EtOAc, 3:1). Compound 12d (62 mg,
purified by flash chromatography on SiO2.
1
2
2%) as
a yellow oil. Rf =0.28 (petrol/EtOAc, 3:1). H NMR
(
ꢁ)-(3aS,4S,5S,10bS)-7-Hydroxy-9-methoxy-4-methyl-4-(4-meth-
ylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-
H-5,10b-methanobenzo[e]azulene-6,11-dione (13b) and (ꢁ)-
3aS,4S,5S,10bS)-7,9-dihydroxy-4-methyl-4-(4-methylpent-3-en-
(
500 MHz, CDCl ): d=6.52 (d, J=2.1 Hz, 1H), 6.38 (d, J=2.1 Hz,
3
1
1
2
3
2
9
2
1
H), 5.01 (t, J=7.0 Hz, 1H), 3.90 (s, 3H), 3.88 (s, 3H), 3.10 (d, J=
5.1 Hz, 1H), 2.69 (d, J=15.0 Hz, 1H), 2.39–2.31 (m, 3H), 2.02 (m,
H), 1.77 (s, 3H), 1.65 (s, 3H), 1.63 (s, 3H), 1.59 (m, 1H), 1.55 (s,
6
(
13
1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-
methanobenzo[e]azulene-6,11-dione (2): Method A: 12b
H), 1.29 (m, 1H), 1.23 ppm (s, 3H); C NMR (125 MHz, CDCl ): d=
3
09.0, 196.1, 164.6, 163.6, 153.3, 132.9, 131.5, 124.5, 122.8, 115.6,
9.6, 97.1, 73.6, 62.7, 59.4, 56.3, 55.7, 42.3, 39.4, 31.9, 29.4, 25.8,
3.2, 21.2, 20.9, 17.8, 16.0, 10.9 ppm; IR (neat): n˜ =3377, 2980,
(
195 mg, 0.46 mmol), LiCl (293 mg, 6.92 mmol), DMF (5 mL). Chro-
matographic eluent: (petrol/ EtOAc, 5:1). Compound 13b (54 mg,
29%) as a white solid. R =0.50 (petrol/EtOAc, 4:1). mp=130–
1358C. H NMR (500 MHz, CDCl ) d= =12.62 (s, 1H), 6.43 (d, J=
.1 Hz, 1H), 6.34 (d, J=2.1 Hz, 1H), 5.02 (t, J=7.0 Hz, 1H), 3.85 (s,
ꢀ1
f
751, 1662, 1597, 1458, 1381, 1159 cm ; HRMS (ESI): calculated for
1
+
3
C H NaO 459.2511 [M+Na] , found 459.2506.
2
8
36
4
2
(
(
ꢁ)-(3aR,5R,10bS)-5-Chloro-7,9-dimethoxy-4,4-dimethyl-2-
propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methano-
3H), 3.26 (s, 1H), 3.08 (d, J=15.4 Hz, 1H), 2.61 (d, J=15.3 Hz, 1H),
2.37–2.29 (m, 2H), 2.22 (dd, J=9.2, 5.3 Hz, 1H), 2.19–2.09 (m, 1H),
1.95–1.84 (m, 1H), 1.77 (s, 3H), 1.65 (s, 3H), 1.65 (s, 3H), 1.60 (s,
3H), 1.51 (td, J=12.0, 4.8 Hz, 1H), 1.29 (td, J=12.0, 4.8 Hz, 1H),
benzo[e]azulene-6,11-dione (12e): 11 e (1.33 g, 34.0 mmol), CHCl3
(
300 mL), Pb(OAc)4 (1.58 g, 35.7 mmol). Chromatographic eluent:
13
(
petrol/ EtOAc, 3:1). Compound 12e (614 mg, 47%) as a white
0.97 ppm (s, 3H); C NMR (125 MHz, CDCl ) d=204.0, 199.5, 166.3,
3
1
solid. Rf =0.20 (petrol/EtOAc, 2:1); mp=190–1948C. H NMR
166.2, 150.5, 132.5, 132.0, 123.6, 123.4, 111.3, 102.2, 98.9, 75.6, 64.2,
58.5, 55.7, 41.4, 41.3, 30.7, 28.5, 25.7, 23.1, 21.1, 20.8, 20.7,
17.6 ppm; IR (neat): n˜ =2909, 1755, 1611, 1429, 1348, 1203, 971,
(
500 MHz, CDCl ): d=6.53 (d, J=1.9 Hz, 1H), 6.41 (d, J=1.9 Hz,
3
1
1
1
H), 3.92 (s, 3H), 3.91 (s, 3H), 3.21 (d, J=15.2 Hz, 1H), 2.75 (d, J=
ꢀ1
5.2 Hz, 1H), 2.54–2.45 (m, 1H), 2.39–2.30 (m, 2H), 1.78 (s, 3H),
820 cm . Further elution gave 2 (62 mg, 34%) as a white solid.
13
1
.66 (s, 3H), 1.14 (s, 3H), 0.90 ppm (s, 3H); C NMR (125 MHz,
Rf =0.25 (petrol/EtOAc, 2:1); mp=76–808C. H NMR (500 MHz,
CDCl ): d=200.7, 187.8, 165.1, 163.8, 151.4, 131.6, 123.8, 114.9,
CDCl ) d=12.54 (s, 1H), 6.38 (d, J=1.8 Hz, 1H), 6.28 (d, J=1.8 Hz,
3
3
1
2
1
4
00.0, 97.1, 89.7, 61.3, 60.0, 56.2, 55.7, 41.7, 30.7, 29.7, 24.1, 21.1,
1H), 5.01 (t, J=7.0 Hz, 1H), 3.27 (s, 1H), 3.08 (d, J=15.4 Hz, 1H),
2.59 (d, J=15.4 Hz, 1H), 2.38–2.30 (m, 2H), 2.23 (dd, J=9.1, 5.4 Hz,
1H), 2.18–2.09 (m, 1H), 1.95–1.84 (m, 1H), 1.77 (s, 3H), 1.65 (s, 3H),
1.65 (s, 3H), 1.59 (s, 3H), 1.52 (dt, J=12.0, 4.8 Hz, 1H), 1.29 (dt, J=
0.8, 19.6 ppm; IR (neat): n˜ =2986, 1768, 1682, 1600, 1565, 1452,
ꢀ
1
204, 1159, 727 cm ; HRMS (ESI): calculated for C H ClO Na
22
25
4
+
11.1339 [M+Na] , found 411.1335.
13
1
2.0, 4.8 Hz, 1H), 0.98 ppm (s, Hz, 3H); C NMR (125 MHz, CDCl3)
d=204.0, 199.5, 165.9, 162.9, 151.5, 132.4, 132.0, 123.6, 123.5,
11.6, 110.8, 102.1, 101.8, 75.6, 64.3, 58.5, 41.4, 41.3, 30.7, 28.6, 25.7,
(
ꢁ)-(3aS,5S,10bS)-7,9-Dimethoxy-4,4-dimethyl-2-(propan-2-yli-
dene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methanobenzo[e]azu-
lene-6,11-dione (12 f): 11 f (1.21 g, 3.39 mmol), CHCl3 (200 mL),
Pb(OAc)4 (1.58 g, 3.56 mmol). Chromatographic eluent: (petrol/
1
2
1
3
3.1, 21.1, 20.8, 17.6 ppm. IR (neat): n˜ =3340, 2916, 1761, 1623,
ꢀ1
451, 1160, 1037, 754 cm ; HRMS (ESI): calculated for C H O
2
5
29
4
EtOAc, 3:1). Compound 12 f (422 mg, 36%) as a white solid. R =
ꢀ
f
93.2071 [M-H] , found 393.2070.
1
0
.10 (petrol/EtOAc, 2:1); mp=174–1788C. H NMR (500 MHz,
CDCl ): d=6.55 (d, J=1.7 Hz, 1H), 6.41 (d, J=1.7 Hz, 1H), 3.92 (s,
(ꢁ)-(3aR,4S,5R,10bS)-5-Bromo-7-hydroxy-9-methoxy-4-methyl-4-
3
3
1
H), 3.90 (s, 3H), 3.15 (s, 1H), 3.13 (d, J=15.5 Hz, 1H), 2.66 (d, J=
5.5 Hz, 1H), 2.42–2.28 (m, 2H), 2.25 (dd, J=9.6, 4.3 Hz, 1H), 1.78
(4-methylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexa-
hydro-6H-5,10b-methanobenzo[e]azulene-6,11-dione (13c) and
(ꢁ)-(3aR,4S,5R,10bS)-5-bromo-7,9-dihydroxy-4-methyl-4-(4-meth-
ylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-
6H-5,10b-methanobenzo[e]azulene-6,11-dione (14c): Method B:
12c (100 mg, 0.199 mmol), LiCl (169 mg, 3.99 mmol), DMF (2 mL).
Chromatographic eluent: (petrol/ EtOAc, 10:2). Compound 13c
13
(
(
s, 3H), 1.65 (s, 3H), 1.14 (s, 3H), 0.96 ppm (s, 3H); C NMR
125 MHz, CDCl ): d=205.2, 192.9, 164.7, 163.6, 152.6, 132.5, 123.1,
3
115.4, 100.1, 97.0, 77.7, 64.8, 59.3, 56.2, 55.5, 37.0, 30.2, 29.4, 27.4,
2
1
4.5, 21.1, 20.8 ppm; IR (neat): n˜ =2910, 1751, 1666, 1599, 1568,
ꢀ1
452, 1212, 1165, 1062, 846, 671 cm ; HRMS (ESI): calculated for
+
C H O 355.1909 [M+H] , found 355.1907.
(43 mg, 34%) as a white solid. R =0.90 (petrol/EtOAc, 3:1); mp=
2
2
27
4
f
1
1
11–1138C. H NMR (500 MHz, CDCl ): d=12.33 (s, 1H), 6.43 (d, J=
3
General procedure for the synthesis of compounds 1, 2, 14c–f:
Method A: Dimethylated compound (1 equiv) and LiCl (15 equiv)
were dissolved in DMF (0.1m). The mixture was heated at 1358C
and stirred for 4 h. The mixture was cooled, quenched with 1m
HCl and then extracted with EtOAc (ꢃ3). The combined organics
2
3
2
1
.2 Hz, 1H), 6.36 (d, J=2.2 Hz, 1H), 5.00 (t, J=6.9 Hz, 1H), 3.86 (s,
H), 3.14 (d, J=15.4 Hz, 1H), 2.71 (d, J=15.5 Hz, 1H), 2.50–2.41 (m,
H), 2.35 (dd, J=9.1, 3.9 Hz, 1H), 2.13 (m, 1H), 1.89–1.82 (m, 1H),
.77 (s, 3H), 1.75–1.68 (m, 1H), 1.65 (s, 6H), 1.58 (s, 3H), 1.36–1.20
13
(m, 1H), 1.02 ppm (s, 3H); C NMR (125 MHz, CDCl ): d=199.1,
3
were washed with brine (ꢃ3), dried over anhydrous MgSO , filtered
4
1
9
94.4, 166.9, 166.7, 149.9, 132.4, 131.6, 124.2, 123.6, 110.7, 102.6,
9.3, 89.2, 61.6, 59.0, 56.1, 45.2, 39.6, 32.4, 29.5, 25.8, 22.9, 21.3,
and concentrated in vacuo. LiCl (15 equiv) and DMF (0.1m) were
&
ChemMedChem 2017, 12, 1 – 9
6
ꢂ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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