and EtOAc); HRMS (ESI, M++Na) calcd for C21H17BrO2Na
403.0310, found 403.0312; H NMR (400 MHz, CDCl3): δ 8.02
(d, J = 8.8 Hz, 2H), 7.63-7.56 (m, 6H), 7.46-7.34 (m, 3H), 6.94
(d, J = 9.2 Hz, 2H), 6.43 (s, 1H), 3.85 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 189.49, 163.93, 141.85, 140.14, 135.10, 131.53
(2x), 129.48 (2x), 128.77, 127.62 (4x), 127.05 (2x), 126.81,
114.02 (2x), 55.49, 50.78.
C16H14O4Na 293.0790, found 293.0792; 1H NMR (400 MHz,
CDCl3): δ 7.93 (d, J = 8.8 Hz, 4H), 6.95 (d, J = 9.6 Hz, 4H), 3.86
(s, 6H); 13C NMR (100 MHz, CDCl3): δ 193.46 (2x), 164.80 (2x),
132.29 (4x), 126.20 (2x), 114.23 (4x), 55.58 (2x).
ACCEPTED MANUSCRIPT
1
4.2.14. 1-(3,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)ethane-1,2-
dione (6b).24 Yield = 85% (255 mg); Colorless solid; mp = 122-
o
123 C (recrystallized from hexanes and EtOAc); HRMS (ESI,
1
4.2.7. 2-Bromo-1-(4-methoxyphenyl)-2-(naphthalen-2-yl)ethan-1-
one (3g). Yield = 85% (301 mg); brown gum; HRMS (ESI,
M++Na) calcd for C17H16O5Na 323.0895, found 323.0893; H
NMR (400 MHz, CDCl3): δ 7.94 (dt, J = 2.0, 8.8 Hz, 2H), 7.59
(d, J = 2.0 Hz, 1H), 7.48 (dd, J = 2.0, 8.4 Hz, 1H), 6.96 (dt, J =
2.0, 8.8 Hz, 2H), 6.88 (d, J = 8.4 Hz, 1H), 3.95 (s, 3H), 3.94 (s,
3H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 193.63,
193.32, 164.84, 154.79, 149.51, 132.35 (2x), 126.40, 126.33,
126.27, 114.27 (2x), 110.29, 110.27, 56.20, 56.06, 55.61.
1
M++Na) calcd for C19H15BrO2Na 377.0153, found 377.0149; H
NMR (400 MHz, CDCl3): δ 8.26 (d, J = 8.4 Hz, 1H), 7.90 (d, J =
8.0 Hz, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.4 Hz, 1H),
7.69-7.65 (m, 1H), 7.60-7.54 (m, 2H), 7.39-7.35 (m, 1H), 7.22 (s,
1H), 6.78 (d, J = 9.2 Hz, 2H), 3.74 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 189.57, 163.71, 134.15, 132.38, 131.28 (2x), 129.97,
129.90, 129.15, 127.47, 127.17, 126.73, 126.26, 125.65, 122.56,
113.91 (2x), 55.34, 51.26.
4.2.15. 1-(Benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)ethane-
1,2-dione (6c).25 Yield = 87% (247 mg); Colorless solid; mp =
o
104-105 C (recrystallized from hexanes and EtOAc); HRMS
4.2.8. 2-Bromo-1-(4-methoxyphenyl)-2-(p-tolyl)ethan-1-one (3h).
Yield = 81% (258 mg); Colorless solid; mp = 49-50 oC
(recrystallized from hexanes and EtOAc); HRMS (ESI, M++Na)
calcd for C16H15BrO2Na 341.0153, found 341.0150; 1H NMR
(400 MHz, CDCl3): δ 7.97 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 8.0
Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.36
(s, 1H), 3.85 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 189.59, 163.83, 139.08, 133.32, 131.51 (2x), 129.70 (2x),
128.88 (2x), 114.29, 113.97 (2x), 55.49, 51.51, 21.20.
(ESI, M++Na) calcd for C16H12O5Na 307.0582, found 307.0588;
1H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 8.8 Hz, 2H), 7.48 (d,
J = 8.4 Hz, 1H), 7.47 (s, 1H), 6.96 (d, J = 8.8 Hz, 2H), 6.85 (d, J
= 8.4 Hz, 1H), 6.07 (s, 2H), 3.88 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 193.14, 193.09, 164.88, 153.29, 148.55, 132.33 (2x),
128.05, 127.78, 126.17, 114.28 (2x), 108.36, 108.33, 102.15,
55.61.
4.2.16. 1-(2,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)ethane-1,2-
dione (6d). Yield = 73% (219 mg); Colorless solid; mp = 66-67
oC (recrystallized from hexanes and EtOAc); HRMS (ESI,
4.2.9. 2-Bromo-2-(4-fluorophenyl)-1-(4-methoxyphenyl)ethan-1-
one (3i).20 Yield = 86% (277 mg); Colorless solid; mp = 99-100
oC (recrystallized from hexanes and EtOAc); HRMS (ESI,
M++Na) calcd for C15H12BrFO2Na 344.9902, found 344.9897; 1H
NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8.8 Hz, 2H), 7.53 (dd, J
= 5.2, 12.0 Hz, 2H), 7.07-7.02 (m, 2H), 6.93 (d, J = 8.8 Hz, 2H),
6.34 (s, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
189.41, 164.01, 162.82 (d, J = 247.9 Hz), 132.05 (d, J = 3.8 Hz),
131.47 (2x), 131.04 (d, J = 8.4 Hz, 2x), 126.64, 115.85 (d, J =
21.9 Hz, 2x), 114.05 (2x), 55.50, 49.32.
1
M++Na) calcd for C17H16O5Na 323.0895, found 323.0890; H
NMR (400 MHz, CDCl3): δ 8.01 (d, J = 8.8 Hz, 1H), 7.87 (d, J =
8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.64 (dd, J = 2.0, 8.8 Hz,
1H), 6.37 (d, J = 2.0 Hz, 1H), 3.87 (s, 6H), 3.56 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 193.46, 192.98, 166.67, 163.93,
162.41, 132.62, 131.55 (2x), 126.20, 117.28, 113.97 (2x), 106.88,
98.30, 55.70, 55.65, 55.46.
4.3. A representative synthetic procedure of skeleton 4 is as
follows:
4.2.10.
2-Bromo-2-(2-methoxyphenyl)-1-(4-
NaCN (sodium cyanide, 60 mg, 1.2 mmol) was added to a
solution of substituted 3 (1.0 mmol) in the co-solvent of dioxane
and water (10 mL, v/v = 9:1) at rt. The reaction mixture was
stirred at reflux for 18 h. The reaction mixture was cooled to 25
oC. Saturated NaHCO3 (5 mL) was added to the reaction mixture
and the solvent was concentrated. The residue was diluted with
water (10 mL) and the mixture was extracted with EtOAc (3 x 20
mL). The combined organic layers were washed with brine,
dried, filtered and evaporated to afford crude product (3a-I was
the representative data). Next, BF3.OEt2 (71 mg, 0.5 mmol) was
added to a solution of the crude product without further
purification in CH2Cl2 (5 mL) at rt. The reaction mixture was
stirred at rt for 2 h. Saturated NaHCO3 (5 mL) was added to the
reaction mixture and the solvent was concentrated. The residue
was diluted with water (10 mL) and the mixture was extracted
with CH2Cl2 (3 x 20 mL). The combined organic layers were
washed with brine, dried, filtered and evaporated to afford crude
product. Purification on silica gel (hexanes/EtOAc = 10/1 ~ 6/1)
afforded skeleton 4.
methoxyphenyl)ethan-1-one (3j). Yield = 83% (277 mg); brown
gum; HRMS (ESI, M++Na) calcd for C16H15BrO3Na 357.0102,
1
found 357.0098; H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 9.2
Hz, 2H), 7.50 (dd, J = 1.6, 7.6 Hz, 1H), 7.31-7.27 (m, 1H), 6.94
(s, 1H), 6.90-6.86 (m, 4H), 3.93 (s, 3H), 3.83 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 190.04, 163.73, 155.43, 131.26 (2x),
130.54, 130.33, 126.99, 125.01, 121.40, 113.88 (2x), 110.97,
55.80, 55.44, 46.46.
4.2.11. 2-Bromo-1-phenylpropan-1-one (3k).21 Yield = 88% (187
mg); Colorless oil; HRMS (ESI, M++Na) calcd for C9H9BrONa
1
234.9735, found 234.9732; H NMR (400 MHz, CDCl3): δ 8.05-
8.02 (m, 2H), 7.62-7.57 (m, 1H), 7.51-7.47 (m, 2H), 5.30 (q, J =
6.8 Hz, 1H), 1.91 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 193.31, 133.98, 133.66, 128.89 (2x), 128.72 (2x),
41.43, 20.09.
4.2.12. 2-Bromo-1-phenylbutan-1-one (3l).22 Yield = 84% (190
mg); yellow gum; HRMS (ESI, M++Na) calcd for C10H11BrONa
1
248.9891, found 248.9888; H NMR (400 MHz, CDCl3): δ 8.04-
8.01 (m, 2H), 7.62-7.57 (m, 1H), 7.51-7.46 (m, 2H), 5.08 (dd, J =
6.4, 8.0 Hz, 1H), 2.19 (m, 2H), 1.09 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ 193.23, 134.49, 133.64, 128.81 (2x),
128.74 (2x), 49.03, 26.88, 12.16.
4.4.1. 2,3-Diphenyloxirane-2-carbonitrile (3a-I). Two isomers
(ratio = 3 : 1). Yield = 86% (190 mg); Colorless oil; HRMS (ESI,
1
M++Na) calcd for C15H11NONa 244.0738, found 244.0735; H
NMR (400 MHz, CDCl3): δ 7.50-7.48 (m, 2H), 7.35-7.12 (m,
8H), 4.80 (s, 0.7H), 4.21 (s, 0.3H).
4.2.13. 1,2-Bis(4-methoxyphenyl)ethane-1,2-dione (6a).23 Yield =
o
88% (238 mg); Colorless solid; mp = 128-129 C (recrystallized
4.3.2. 2,2-Diphenylacetonitrile (4a).26 Yield = 81% (156 mg);
o
from hexanes and EtOAc); HRMS (ESI, M++Na) calcd for
Colorless solid; mp = 58-59 C (recrystallized from hexanes and