4350
B.M. O’Keefe et al. / Tetrahedron 67 (2011) 4344e4351
135.3, 134.7, 129.4, 128.1, 114.3, 111.7, 95.0, 89.4, 55.4, 19.6; IR (neat)
2961, 2183, 1643 cmꢁ1; mass spectrum (CI) m/z 265.1229 [C18H17O2
(Mþ1) requires 265.1229], 529, 266, 265.
Saturated NH4Cl (1 mL) was added, and the resultant mixture was
extracted with EtOAc (3ꢂ1 mL). The combined organic layers were
washed with brine (4 mL), dried (Na2SO4), filtered, and concen-
trated under reduced pressure to give 0.015 g, >99% of 2 as a yellow
5.3.14. 1-(20-Methoxy-40,60-dimethylphenyl)-3-phenylprop-2-yn-1-
one (40). Method C (3 mol % PPh3 was added to the reaction
mixture and the pressure was increased to 170 psi of CO): 0.05 g,
67% of 40 as a yellow oil (9:1 hexanes/EtOAc): 1H NMR (400 MHz,
oil: 1H NMR (400 MHz, CDCl3)
d 7.52e7.31 (comp, 2H), 6.96 (d,
J¼7.0 Hz, 1H), 6.63 (s, 1H), 6.58 (d, J¼1.8 Hz, 1H), 6.40 (d, J¼1.8 Hz,
1H), 3.98 (s, 3H), 3.97 (s, 3H), 3.95 (s, 3H), 3.94 (s, 3H); 13C NMR
(100 MHz, CDCl3) 177.4, 164.0, 160.9, 160.3, 159.8, 151.7, 149.0, 123.9,
119.2,111.1, 108.6, 108.0, 106.0, 96.0, 92.8, 56.2, 56.1, 56.0, 55.6; mass
spectrum (CI) m/z 343.1182 [C19H19O6 (Mþ1) requires 343.1182].
CDCl3)
2H), 6.64 (s, 1H), 6.62 (s, 1H), 3.85 (s, 3H), 2.35 (s, 3H), 2.33 (s, 3H);
13C NMR (100 MHz, CDCl3)
181.0, 158.0, 141.9, 137.5, 133.0, 130.4,
d 7.55e7.53 (comp, 2H), 7.43e7.39 (m, 1H), 7.36e7.32 (comp,
d
128.5, 126.7, 124.0, 120.6, 110.0, 90.9, 90.1, 55.8, 21.7, 19.5; IR (neat)
2925, 2193, 1644 cmꢁ1; mass spectrum (ESI) m/z 265.12231
[C18H17O2 (Mþ1) requires 265.1228], 288, 265, 163.
Acknowledgements
We thank the National Institutes of Health (GM 25439 and GM
31077) and the Robert A. Welch Foundation (F-0652) for support of
this research. N. S. also thanks the Arnold and Mabel Beckman
Foundation for an undergraduate research fellowship.
5.3.15. 2-Iodo-1-methoxy-3,5-dimethylbenzene (39). Sodium hy-
dride (0.32 g, 8.1 mmol) was added in one portion to a solution of 2-
iodo-3,5-dimethylphenol (1.0 g, 4.0 mmol) and methyl iodide
(1.3 mL, 20.2 mmol) in DMF (20 mL) at 0 ꢀC. After gas evolution had
subsided, the cooling bath was removed, and the mixture was
stirred at ambient temperature for 30 min. The mixture was
recooled to 0 ꢀC, whereupon saturated NH4Cl (10 mL) was slowly
added. The mixture was diluted with EtOAc (50 mL), and the layers
were separated. The organic layer was washed with H2O (4ꢂ50 mL)
and brine (50 mL), dried (MgSO4), filtered, and concentrated. The
crude residue was purified by flash column chromatography, elut-
ing with hexanes/ethyl acetate (9:1), to afford 0.95 g (90%) of 39 as
References and notes
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a white solid: mp¼43e44 ꢀC; 1H NMR (400 MHz, CDCl3)
d 6.72 (s,
1H), 6.46 (s, 1H), 3.85 (s, 3H), 2.43 (s, 3H), 2.30 (s, 3H); 13C NMR
(100 MHz, CDCl3)
d 157.8, 142.7, 138.7, 123.2, 109.0, 88.8, 56.2, 28.4,
21.1; IR (neat) 2936, 1572, 1457 cmꢁ1; mass spectrum (ESI) m/z
262.99273 [C9H12IO (Mþ1) requires 262.9927], 263, 262.
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5.3.16. 3-(30,40-Dimethoxyphenyl)-1-(200,400,600-trimethoxyphenyl)
prop-2-yn-1-one (44). Method C: (3 mol % PPh3 was added to the
reaction mixture and the pressure was increased to 170 psi of CO):
0.06 g, 52% of 44 as a yellow oil (9:1 hexanes/EtOAc): 1H NMR
(400 MHz, CDCl3)
6.80 (d, J¼8.2 Hz, 1H), 6.11 (s, 2H), 3.87 (s, 3H), 3.84 (s, 3H), 3.82 (s,
9H); 13C NMR (100 MHz, CDCl3)
163.5, 160.1, 151.1, 148.6, 127.1,
d
7.16 (dd, J¼8.2, 1.7 Hz, 1H), 7.03 (d, J¼1.7 Hz, 1H),
d
115.4, 112.9, 112.5, 110.9, 90.7, 56.1, 55.9, 56.1, 55.9; IR (neat) 2960,
2190, 1643 cmꢁ1; mass spectrum (CI) m/z 357.1337 [C20H21O6
(Mþ1) requires 357.1338].
5.3.17. 3-(30,40-Dimethoxyphenyl)-1-(200-hydroxy-400,600-dimethox-
yphenyl)prop-2-yn-1-one (45). BBr3 (0.004 mL, 0.043 mmol) was
added dropwise to a solution of 44 (0.015 g, 0.042 mmol) in CH2Cl2
(1 mL) at ꢁ78 ꢀC. Stirring was continued for 1 min, whereupon
MeOH was added. The cooling bath was removed and the solution
was warmed to room temperature. The mixture was extracted with
CH2Cl2 (3ꢂ1 mL). The combined organic layers were washed with
H2O (3 mL), brine (3 mL), dried (Na2SO4), and concentrated under
reduced pressure. The crude residue was purified by flash column
chromatography, eluting with CH2Cl2, to afford 0.0042 g (37%) of 45
as a yellow oil: 1H NMR (400 MHz, CDCl3)
d 13.65 (s, 1H), 7.25e7.23
17. Fusano, A.; Fukuyama, T.; Nishitani, S.; Inouye, T.; Ryu, I. Org. Lett. 2010, 12, 2410.
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20. O’Keefe, B. M.; Mans, D. M.; Kaelin, D. E., Jr.; Martin, S. F. J. Am. Chem. Soc. 2010,
132, 15528.
(m, 1H), 7.11 (d, J¼1.8 Hz, 1H), 6.86 (d, J¼8.2 Hz, 1H), 6.05 (d,
J¼2.2 Hz,1H), 5.92 (d, J¼2.2 Hz,1H), 3.92 (s, 3H), 3.91 (s, 3H), 3.89 (s,
3H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 177.5, 168.2, 167.2,
162.5, 151.4, 148.8, 127.2, 115.4, 113.0, 111.0, 107.0, 96.1, 93.4, 91.0,
89.3, 56.0, 55.70, 55.66; IR (neat) 3350, 1645 cmꢁ1; mass spectrum
(CI) m/z 343.1183 [C19H18O6 (Mþ1) requires 343.1182].
21. (a) Liang, B.; Huang, M.; You, Z.; Yiong, Z.; Lu, K.; Fathi, R.; Chen, J.; Yong, Z. J.
Org. Chem. 2005, 70, 6097; (b) Nakatani, K.; Okamoto, A.; Saito, I. Tetrahedron
1996, 52, 9427.
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S. L. Org. Lett. 2004, 6, 2649.
24. (a) Calo, V.; Giannnoccaro, P.; Nacci, A.; Monopoli, A. J. Organomet. Chem. 2002,
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M.; Reisinger, C.-P.; Weskamp, T. J. Organomet. Chem. 2001, 617e618, 616; (c)
Ma, Y.; Song, C.; CHai, Q.; Ma, C.; Andrus, M. B. Synthesis 2003, 18, 2886; (d)
5.3.18. Luteolin (2). Cs2CO3 (0.043 g, 0.131 mmol) was added in one
portion to a solution of 45 (0.015 g, 0.044 mmol) in acetone
(0.44 mL) at ambient temperature. Stirring was continued for
10 min, whereupon the mixture was diluted with H2O (1 mL).