8784
F.C. Gaenzler et al. / Tetrahedron 65 (2009) 8781–8785
1685, 1597, 1563, 1405, 1271, 1003, 905, 751 cmꢂ1. MS m/z: 174 (P,
24), 130 (13), 129 (100), 128 (59), 127 (28), 115 (11), 77 (16), 63 (10),
51 (18).
MgSO4, filtered, and concentrated in vacuo. The residue was puri-
fied by flash column chromatography (silica gel, 100% hexanes) to
yield 2.45 g (11.72 mmol, 83%) of 17 as a yellow oil.23a 1H NMR
(CDCl3):
d
7.56 (m, 2H), 7.26 (m, 1H), 7.07 (td, 1H, J¼1.7, 7.6 Hz), 6.92
3.1.3. 1-(2-Bromophenyl)1,3-butadiene, 17. Wittig protocol. A solu-
tion of 2.2 M n-butyllithium in hexanes (10 mL, 22 mmol) was
added dropwise to a sonicated suspension (in a sonic cleaning bath)
of commercial prop-2-enyltriphenylphosphonium bromide (7.66 g,
20 mmol) in dry THF under nitrogen. After 15 min, 2-bromo-
benzaldehyde (16, 3.7 g, 20 mmol) was added to the red reaction at
ambient temperature over 3 h, and stirred for 3 h without sonica-
tion until consumption of the aldehyde was complete, as monitored
by TLC. The solvent was removed in vacuo and the residue tritu-
rated with ether to precipitate triphenylphosphine oxide. The
mixture was filtered through a silica gel pad, the filtrate concen-
trated in vacuo, and purified by flash column chromatography
(silica; hexane/CH2Cl2¼95:5) to give 2.6 g (12.43 mmol, 62%) of 17
(d, 1H, J¼15.4 Hz), 6.74 (m, 1H), 6.57 (m, 1H), 5.38 (dd, 1H, J¼1.4,
16.5 Hz), 5.24 (dd, 1H, J¼1.4, 9.7 Hz); 13C NMR (CDCl3):
d 137.0,
131.9, 131.2, 130.3, 128.6, 127.6,126.5, 125.4, 117.6,116.6; MS (ES) m/z
210 (10), 208 (10), 129 (100).
3.2.2. 3-(2-Buta-1,3-dienyl-benzoyl)-3H-oxazol-2-one, 20. 1-(1,3-Buta-
dienyl)benzoic acid (15, 0.50 g, 2.87 mmol) was added to oxalyl
chloride (5 mL). Evolution of gas started immediately, and after 10 min
heat was applied. The mixture was refluxed under N2 for 5 h. The
reaction was concentrated in vacuo, a sample analyzed by MS and IR to
confirm the presence of the acid chloride, and it was used without
further purification. MS (EI) m/z: 194 (Pþ2, 9), 192 (P, 21), 157 (100),
129 (100), 128 (86), 127 (43), 102 (19), 77 (14), 75 (10), 63 (14), 51 (19);
as a mixture of E and Z isomers.23a 1H NMR (CDCl3):
6.36, 6.51, 6.78 (sets of dd), 6.93, 7.28, 7.36, 7.58; 13C NMR (CDCl3):
119.1, 120.5, 124.2, 126.8, 127.1, 127.7, 128.9, 129.0, 130.1, 131.4,
d
5.21, 5.38,
IR: 1770, 1650, 1595, 1560, 1469, 1183, 1102, 1002, 867, 649 cmꢂ1
.
Triethylamine (0.70 mL, 5.03 mmol) was added dropwise to a solution
of 2-(1,3-butadienyl)benzoyl chloride (0.75 g, 3.89 mmol) and 2-oxa-
zolone (11, 0.43 g, 5.03 mmol) in acetonitrile (25 mL). The reaction
mixture was stirred at room temperature overnight, concentrated, and
the residue added to a mixture of water (25 mL) and Et2O (25 mL). The
layers were separated and the aqueous layer extracted with Et2O
(2ꢁ25 mL). The combined organic extracts were dried over MgSO4,
filtered, and concentrated in vacuo to yield 0.83 g (3.44 mmol, 88%) of
d
131.5, 132.0, 132.4, 132.9, 133.0, 133.3, 137.0, 137.2, 137.4; IR (film):
3085, 3057, 1815, 1596, 1558, 1464, 1432, 1025, 1000, 946, 906, 750,
734 cmꢂ1; MS m/z: 210(Pþ2, 5), 208 (P, 5), 129 (100), 128 (77), 127
(30), 102 (11), 75 (11), 64 (13), 63 (18), 51 (28), 50 (16).
3.1.4. 1-(2-Bromophenyl)but-3-en-1-ol, 18. Magnesium turnings
(0.83 g, 34.26 mmol) in dry Et2O (10 mL) were added to a flame-
dried, three-neck flask, fitted with a reflux condenser and addition
funnel. A solution of allyl bromide (3.0 mL, 34.26 mmol) in Et2O
(20 mL) was added dropwise, and the reaction was refluxed for 5 h.
19. 1H NMR (CDCl3):
d
7.66 (d, 1H, J¼6 Hz), 7.52 (m, 1H), 7.30–7.44 (m,
3H), 6.90 (d, 1H, J¼3 Hz), 6.72 (m, 2H), 6.47 (m, 1H), 5.38 (d, 1H,
J¼18 Hz), 5.25 (d, 1H, J¼9.0 Hz); 13C NMR (CDCl3):
d 166.2, 150.3, 136.6,
135.9, 133.3, 131.5, 130.7, 130.3, 128.2, 128.0, 127.1, 126.0, 119.4, 112.4;
IR (cmꢂ1): 3155, 2925, 1788, 1701, 1598, 1481, 1357, 1281,
1226, 1181, 1117, 1067, 1027, 1005, 933, 867, 750, 697, 663; MS (ES)
m/z 241 (8), 157 (100), 129 (100), 102 (11), 77 (16); HRMS (ESþ)
m/z calcd for C14H11NO3: [MþH]þ, 242.0812; found: [MþH]þ,
242.0819.
After cooling to room temperature,
a solution of 2-bromo-
benzaldehyde (16, 2.0 mL, 17.13 mmol) in Et2O (20 mL) was added
dropwise, and then the reaction was refluxed overnight. The re-
action was quenched with saturated NH4Cl and extracted with Et2O
(3ꢁ50 mL). The combined organic extracts were dried over MgSO4,
filtered, and concentrated in vacuo. The residue was purified by
flash column chromatography (25% EtOAc/Hex; Rf¼0.50) to yield
3.21 g (14.1 mmol, 82%) of 18 as a pale yellow oil.23a 1H NMR
3.2.3. 3,3a,10b,10c-Tetrahydro-4-oxa-5a-aza-acephenanthrylene-
5,6-dione, 20 and 21. A solution of 3-(2-buta-1,3-dienyl-benzoyl)-
3H-oxazol-2-one (19, 0.40 g, 1.66 mmol) was refluxed in dry
toluene (10 mL) for 2 days under N2. After cooling, the toluene was
filtered and the stirbar and flask washed with EtOAc to dissolve all
residues that coated those surfaces. The EtOAc was added to the
toluene, all solvents were removed in vacuo. The residue was taken
up in dichloromethane/ethyl acetate and added directly to silica
gel, which allowed purification by flash column chromatography
(gradient 25% EtOAc/Hex to 100% EtOAc) to give 0.22 g (0.91 mmol,
55%) of 20 (all cis) as a white solid, Rf¼0.32 (100% EtOAc). 1H NMR
(CDCl3):
d
7.54 (m, 2H), 7.34 (td, 1H, J¼1.1, 7.5 Hz), 7.13 (td, 1H, J¼1.7,
7.6 Hz), 5.89 (m, 1H), 5.21 (m, 1H), 5.17 (d, 1H, J¼1.1 Hz), 5.10 (dd,
1H, J¼3.4, 8.3 Hz), 2.65 (m, 1H), 2.36 (m, 1H), 2.16 (s, 1H); 13C NMR
(CDCl3):
d 142.9, 134.4, 132.9, 129.0, 127.8, 127.5, 122.0, 118.8, 72.0,
42.3; MS (ES) m/z 227 (14), 225 (17), 185 (87), 183 (100).
3.2. Indium-mediated procedure23b
A suspension of indium metal (4.72 g, 41.12 mmol) was stirred at
35 ꢀC overnight under N2 in a solution of 2-bromobenzaldehyde (16,
6.0 mL, 51.40 mmol), boron trifluoride etherate (6.5 mL,
51.40 mmol), and allyl bromide (4.4 mL, 51.40 mmol) in dry THF
(80 mL). The reaction mixture was diluted with water (50 mL) and
extracted with EtOAc (2ꢁ75 mL). The combined organic extracts
were washed with brine, dried over MgSO4, filtered, and concen-
trated in vacuo to yield a thick colorless oil. Flash column chromato-
graphy (15% EtOAc/Hex) yielded 10.15 g (44.6 mmol, 87%) of 18 as
a colorless oil.
(CDCl3):
d
8.12 (d, 1H, J¼8 Hz), 7.55 (t, 1H, J¼8 Hz), 7.40 (t, 1H,
J¼8 Hz), 7.28 (d, 1H, J¼8 Hz), 5.95 (m, 1H), 5.59 (d, 1H, J¼8 Hz), 5.01
(t, 1H, J¼4 Hz), 4.84 (t, 1H, J¼4 Hz), 3.46 (s, 1H), 2.60 (dd, 1H, J¼8,
16 Hz), 2.27 (d, 1H, J¼16 Hz); 13C NMR (CDCl3):
d 172.5, 160.0, 150.9,
139.4, 133.4, 128.7, 127.8, 127.5, 127.0, 125.2, 70.6, 54.0, 35.7, 26.8;
MS m/z: 241 (P, 44), 198 (13), 197 (54), 196 (16), 181 (10), 180 (38),
170 (11), 157 (95), 156 (49), 141 (15), 129 (100), 128 (82), 127 (33),
115 (28), 102 (10), 89 (15), 77 (21), 76 (12), 75 (10), 63 (21), 51 (20),
50 (13); HRMS (ESþ) m/z calcd for C14H11NO3: [MþH]þ, 242.0812;
found: [MþH]þ, 242.0811. In addition, 0.10 g (0.42 mmol, 25%) of
the 21 (trans) was obtained as a tan solid, Rf¼0.48 (100% EtOAc). 1H
3.2.1. 2-(1,3-Butadienyl)bromobenzene, 17. Bromination–elimination
protocol. A solution of 1-(2-bromophenyl)but-3-en-1-ol (18, 3.21 g,
14.13 mmol), triphenylphosphine (4.45 g, 16.96 mmol), hydroqui-
none (0.28 g, 2.54 mmol), and carbon tetrabromide (5.62 g,
16.96 mmol) were refluxed in dry THF (30 mL) for 30 min. Triethyl-
amine (7.9 mL, 56.52 mmol) was added dropwise and the reaction
was refluxed overnight. Water (75 mL) was added to the reaction
mixture, which was extracted with hexanes (3ꢁ100 mL). The
combined organic extracts were washed with brine, dried over
NMR (CDCl3):
d
8.11 (d, 1H, J¼6 Hz), 7.58 (m, 1H), 7.44 (m, 2H), 6.50
(m, 1H), 6.09 (m, 1H), 4.70 (m, 1H), 3.96 (t, 1H, J¼18 Hz), 3.65 (d, 1H,
J¼12 Hz), 3.07 (m, 1H), 2.28 (m, 1H); 13C NMR (CDCl3):
d 29.4, 38.6,
58.7, 71.3, 123.6, 126.8, 127.8, 128.0, 129.1, 130.7, 134.0, 138.7, 151.1,
161.2; IR: 2977, 1790 (str), 1678, 1603, 1354, 1303, 1274, 1185, 1025,
749, 676, 662, 541 cmꢂ1; MS m/z: 242 (Pþ1,11), 241 (P, 70),198 (15),
197 (100), 196 (65), 182 (18), 180 (10), 170 (13), 169 (23), 168 (28),
167 (13), 157 (77), 156 (70), 144 (13), 141 (21), 140 (11), 130 (10), 129