FULL PAPERS
Brennan Murphy et al.
16: Yield: 450 mg (50%); Rf =0.58 (1:1 hexane:EtOAc);
mp 145–1508C (MeOH); [a]20: À218.28 (c=1.0, CHCl3); IR
(neat): n=2935, 2836, 2792,D2234, 1499, 1279, 1107, 1021,
were combined and then washed with brine and dried over
Na2SO4, concentrated under vacuum, then purified by
column chromatography (1:1 hexane:EtOAc) to afford 18;
yield: 74 mg (50%).
1
906, 793 cmÀ1; H NMR (600 MHz, CDCl3): d=6.65 (d, J=
8.1 Hz, 1H), 6.56 (d, J=8.1 Hz, 1H), 5.91 (q, J=9.1 Hz,
2H), 5.00 (s, 1H), 3.83 (s, 3H), 3.77 (s, 1H), 3.67 (s, 3H),
3.39 (d, J=6.6 Hz, 1H), 3.27 (dd, J=18.3, 10.6 Hz, 1H),
2.93 (td, J=12.7, 5.5 Hz, 1H), 2.68 (dd, J=12.2, 5.3 Hz,
1H), 2.53–2.44 (m, 2H), 2.40 (s, 3H), 1.89 (dd, J=13.1,
2.5 Hz, 1H); 13C NMR (151 MHz, CDCl3): d=147.0, 142.5,
138.0, 133.2, 126.6, 124.6, 119.9, 117.4, 114.6, 91.4, 79.9, 60.0,
56.9, 53.9, 52.9, 50.5, 45.8, 43.4, 35.2, 32.7, 23.2; MS (EI+):
m/z (rel. %)=382 (7), 311 (95), 297 (50), 255 (22); HR-MS
(ESI): m/z=382.1351, calcd. for C21H22N2O3S: 382.1351;
anal. calcd, for C21H22N2O3S: C 65.95, H 5.80; found: C
65.99, H 5.81.
Method C: To a solution of 16 (170 mg, 0.395 mmol) in
dry MeSO3H (1.15 mL, 11.8 mmol) was slowly added me-
thionine (90 mg, 0.594 mmol). The orange solution was then
heated to 508C and left to stir for 8 h. The reaction was
monitored by HPLC. The reaction mixture was then deca-
nted into ice-water (20 mL) and its acidity was slowly adjust-
ed to pH 8 with 15% aqueous NaOH solution. The aqueous
layer was extracted with CH2Cl2 (3ꢃ10 mL). The organic
layers were combined and then washed with brine and dried
over Na2SO4, concentrated under vacuum and the product
was
hexane:EtOAc) to furnish 18; yield: 73 mg (51%).
Method D: To solution of 16 or 17 (110 mg,
purified
by
column
chromatography
(1:1
17: Yield: 350 mg (38%); Rf =0.50 (1:1 hexane:EtOAc);
mp 164–1658C (MeOH); [a]20: +5.98 (c=1.0, CHCl3); IR
(neat): n=2948, 2802, 2235, D1500, 1284, 1108, 1019, 894,
a
0.287 mmol) in dry CH2Cl2 (5 mL) was slowly added 9-I-9-
BBN (1M in hexanes; 0.86 mL, 0.863 mmol) at room tem-
perature. After four hours, the reaction mixture was then
decanted into ice-water (20 mL) and its acidity was slowly
adjusted to pH 8 with 15% aqueous NaOH solution. The
aqueous layer was extracted with CH2Cl2 (3ꢃ10 mL). The
organic layers were combined and then washed with brine
and dried over Na2SO4, concentrated under vacuum, then
purified by column chromatography (1:1 hexane:EtOAc) to
afford 18 or 19; yield: 80 mg (72%).
760 cmÀ1
;
1H NMR (600 MHz, CDCl3): d=6.66 (d, J=
8.2 Hz, 1H), 6.58 (d, J=8.2 Hz, 1H), 6.00 (d, J=8.8 Hz,
1H), 5.95 (d, J=9.0 Hz, 1H), 4.52 (s, 1H), 4.08 (s, 1H), 3.83
(s, 3H), 3.68 (s, 3H), 3.47 (d, J=6.5 Hz, 1H), 3.26 (d, J=
18.5 Hz, 1H), 2.71 (td, J=12.6, 5.5 Hz, 1H), 2.61 (dd, J=
12.2, 5.3 Hz, 1H), 2.54 (dd, J=18.5, 6.6 Hz, 1H), 2.47–2.40
(m, 1H), 2.39 (s, 3H), 1.81 (dd, J=12.8, 2.7 Hz, 1H);
13C NMR (151 MHz, CDCl3): d=146.5, 142.5, 136.4, 133.1,
126.4, 126.4, 120.2, 117.8, 114.1, 90.8, 80.2, 77.3, 77.0, 76.8,
60.0, 56.6, 53.1, 52.5, 50.7, 45.6, 43.3, 35.7, 32.9, 23.2; MS
(EI+): m/z (rel. %)=382 (7), 311 (95), 296 (50), 255 (22);
HR-MS (ESI): m/z=382.1351, calcd. for C21H22N2O3S;
382.1351; anal. calcd. for C21H22N2O3S: C 65.95, H 5.80;
found: C 66.68, H 5.83.
18: yield: 162 mg (85%); Rf =0.35 (1:1 hexane:EtOAc);
mp 1458C (MeOH); [a]2D0: À199.28 (c=0.25, MeOH); IR
(neat): n=3189, 2936, 2803, 2235, 2069, 1455, 1154, 1102,
1
1028, 943, 905, 757 cmÀ1; H NMR (600 MHz, MeOD): d=
6.53 (d, J=8.1 Hz, 1H), 6.48 (d, J=8.1 Hz, 1H), 6.02–5.95
(m, 2H), 4.83 (s, 1H), 4.15 (s, 1H), 3.62 (s, 3H), 3.42 (d, J=
6.6 Hz, 1H), 3.26 (d, J=18.5 Hz, 1H), 2.87 (td, J=12.7,
5.5 Hz, 1H), 2.64 (dd, J=12.2, 5.2 Hz, 1H), 2.56 (dd, J=
18.5, 6.7 Hz, 1H), 2.46 (td, J=12.3, 3.7 Hz, 1H), 2.37 (s,
3H), 1.81 (dd, J=13.0, 2.8 Hz, 1H); 13C NMR (151 MHz,
MeOD): d=146.9, 140.2, 139.5, 134.1, 126.8, 124.4, 121.2,
118.9, 118.5, 92.7, 81.2, 61.2, 54.0, 53.7, 51.6, 49.9, 46.9, 43.5,
35.4, 33.7, 24.0; MS (EI+): m/z (rel. %)=368 (10), 297 (40),
241 (15), 184 (40); HR-MS (ESI): m/z=368.1194, calcd. for
C20H20N2O3S: 368.1195.
(4R,4aS,7S,7aR,12bS,14S)-9-Hydroxy-7-methoxy-3-
methyl-1,2,3,4,7,7a-hexahydro-4a,7-(epithiomethano)-
4,12-methanobenzofuro
carbonitrile (18)
ACHTUNGERTN[NUNG 3,2-e]isoquinoline-14-
(4R,4aS,7S,7aR,12bS,14R)-9-Hydroxy-7-methoxy-3-
methyl-1,2,3,4,7,7a-hexahydro-4a,7-(epithiomethano)-
4,12-methanobenzofuro
carbonitrile (19)
ACHTUNGERTN[NUNG 3,2-e]isoquinoline-14-
19: Yield: 80 mg (76%); Rf =0.41 (1:1 hexane:EtOAc);
mp 170–1748C (MeOH); [a]2D0: À4.648 (c=0.5, MeOH); IR
(neat): n=3509, 3358, 2926, 2803, 2241, 1638, 1497, 1112,
Method A: To a solution of 16 or 17 (200 mg, 0.52 mmol) in
dry CH2Cl2 (10 mL) was slowly added BBr3 (0.780 g,
3.12 mmol) at 08C under an argon atmosphere. The reaction
mixture was stirred for 20 min at 08C and then removed
from the ice bath and stirred for another 15 min. This mix-
ture was poured into cold water and its acidity was slowly
adjusted to pH 8 with 15% aqueous NaOH solution. The
mixture was then extracted with CH2Cl2 (3ꢃ70 mL). The
combined organic phases were concentrated under vacuum
1030, 891, 761 cmÀ1 1H NMR (600 MHz, DMSO-d6): d=
;
6.49 (d, J=8.0 Hz, 1H), 6.43 (d, J=8.0 Hz, 1H), 6.03 (d, J=
8.9 Hz, 1H), 5.74 (d, J=8.7 Hz, 1H), 4.94 (s, 1H), 4.73 (s,
1H), 3.51 (s, 3H), 3.43 (d, J=6.4 Hz, 1H), 3.10 (d, J=
18.4 Hz, 1H), 2.65 (td, J=12.7, 5.4 Hz, 1H), 2.57–2.45 (m,
8H), 2.27 (s, 3H), 2.26–2.20 (m, 1H), 1.63 (dd, J=12.9,
2.6 Hz, 1H); 13C NMR (151 MHz, DMSO-d6): d=145.2,
138.9, 136.5, 132.9, 126.8, 124.8, 119.9, 118.7, 117.1, 87.1,
79.9, 59.2, 52.5, 51.4, 50.1, 45.2, 42.8, 33.6, 32.2, 22.5; MS
(EI+): m/z (rel. %)=362 (10), 297 (20), 78 (90), 63 (100);
HR-MS (ESI): m/z=368.1195, calcd. for C20H20N2O3S:
368.1195.
and
purified
by
column
chromatography
(1:1
hexane:EtOAc) affording 18 or 19; yield: 162 mg (85%).
Method B: To a solution of 16 (150 mg, 0.4 mmol) in dry
CH2Cl2 (15 mL) was slowly added BF3·SMe2 complex
(0.25 mL, 2.36 mmol) at 08C under an argon atmosphere.
The reaction mixture was stirred for 4 h at 08C and then 2 h
at room temperature. The mixture was then decanted into
ice-water (20 mL) and its acidity was slowly adjusted to
pH 8 with 15% aqueous NaOH solution. The aqueous layer
was extracted with CH2Cl2 (3ꢃ10 mL). The organic layers
Oripavine (2)
From iron tricarbonyl complex 13: Compound 13 (60 mg,
0.137 mmol) was dispersed in acetonitrile (5 mL), the solu-
2684
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 2679 – 2687