2368 J . Org. Chem., Vol. 67, No. 7, 2002
Notes
the coupling product. The coupling product was treated with
NH3‚H2O (0.5 mL) in a solvent of THF and MeOH (1:1, 10 mL)
at 25 °C for 30 min, followed by concentration, and the residue
was purified by flash column chromatography to give the pure
product.
7.27 (s, 1H), 7.02 (s, 1H), 6.91 (s, 1H), 6.84 (d, J ) 9.0 Hz, 2H),
5.15 (s, 2H), 4.77 (s, 2H), 4.06 (s, 3H), 3.83 (s, 3H), 3.77 (s, 3H),
0.93 (s, 9H), 0.09 (s, 6H); 13C NMR δ 191.1, 163.9, 157.0, 149.5,
149.4, 145.0, 142.3, 138.3, 136.8, 132.4, 130.9, 130.4, 128.7, 128.1,
127.4, 122.9, 121.4, 115.8, 113.9, 113.5, 112.0, 110.7, 105.9, 71.0,
65.3, 56.2, 56.1, 55.6, 26.1, 18.5, -5.1; HRMS (ES) [C38H42O7-
Si], m/z (M+ + 1) calcd 639.2778, found 639.2734.
Com p ou n d 9: 98% yield as a white solid; 1H NMR δ 7.61 (d,
J ) 16.0 Hz, 1H), 7.57-7.59 (m, 2H), 7.37-7.38 (m, 3H), 7.28
(d, J ) 2.0 Hz, 1H), 7.02 (d, J ) 2.0 Hz, 1H), 6.34 (d, J ) 16.0
Hz, 1H), 6.25 (s, 1H), 3.96 (s, 3H), 3.82 (s, 3H); 13C NMR δ 167.3,
148.5, 146.8, 144.0, 131.6, 128.5, 128.2, 126.5, 125.6, 122.6, 116.0,
110.1, 109.6, 94.8, 83.3, 56.1, 51.5; MS (APCI) [C19H16O4], m/z
(M+) calcd 308, found 308.
Com p ou n d 12a : 72% yield as a white solid; 1H NMR δ 7.89
(s, 1H), 7.87 (d, J ) 9.0 Hz, 2H), 7.72-7.74 (m, 2H), 7.60 (s,
1H), 7.31-7.34 (m, 3H), 6.84 (d, J ) 9.0 Hz, 2H), 4.12 (s, 3H),
3.91 (s, 3H), 3,84 (s, 3H); 13C NMR (125.7 MHz) δ 190.3, 167.1,
164.2, 157.1, 145.9, 145.2, 132.5, 130.2, 130.0, 129.1, 128.7, 128.2,
127.0, 116.9, 116.1, 114.0, 108.4, 56.5, 55.6, 52.3; HRMS (ES)
[C25H20O6], m/z (M+ + 1) calcd 417.1338, found 417.1313.
Com p ou n d 13a : 90% yield as a white solid; 1H NMR δ 7.92
(d, J ) 9.0 Hz, 2H), 7.87 (s, 1H), 7.58 (s, 1H), 6.99 (d, J ) 9.0
Hz, 2H), 4.60 (s, 3H), 4.09 (s, 3H), 3.92 (s, 3H), 3.91 (s, 2H), 3.40
(s, 3H); 13C NMR δ 188.7, 166.7, 163.9, 158.1, 146.0, 144.9, 131.9,
130.7, 127.8, 126.8, 120.0, 116.4, 113.8, 108.1, 65.2, 58.7, 56.1,
55.4, 52.1; HRMS (ES) [C21H20O7], m/z (M+ + 1) calcd 385.1287,
found 385.1267.
1
Com p ou n d 12: 90% yield as a white solid; H NMR δ 7.85
(d, J ) 2.0 Hz, 1H), 7.57-7.59 (m, 2H), 7.53 (d, J ) 2.0 Hz, 1H),
7.35-7.37 (m, 3H), 6.49 (s, 1H), 3.96 (s, 3H), 3.92 (s, 3H); 13C
NMR δ 166.2, 150.5, 146.3, 131.6, 128.5, 128.2, 127.1, 122.7,
121.9, 111.8, 109.6, 94.7, 83.3, 56.2, 52.0; MS (APCI) [C17H14O4],
m/z (M+) calcd 282, found 282.
Others are known compounds (see ref 6a).
Tw o Differ en t Meth od s for th e Syn th esis of Com p ou n d
8: Meth od 1. To a mixture of compound 5 (0.15 mmol), aromatic
iodide (0.30 mmol), K2CO3 (0.75 mmol), AgBF4 (0.15 mmol), and
Pd(PPh3)4 (0.0075 mmol) in a dry round-bottom flask (25 mL)
was added dry butyl ether (4 mL) by cannulation. The reaction
mixture was degassed for 10 min with CO and then stirred at
50 °C under a balloon pressure of CO for 4 h. The reaction mix-
ture was cooled, filtered through a pad of silica gel, and washed
by EtOAc. The filtrate was concentrated, and the residue was
purified by flash chromatography (8/1 toluene/EtOAc) to give 8
in 30% yield. Meth od 2. A mixture of Pd2(dpa)3 (0.0075 mmol),
2,2′-bipyridine (0.015 mmol), and aromatic iodide (0.30 mmol)
in benzene was stirred for 3 h at 50 °C under N2. To this solution
was added compound 5 in acetonitrile (2 mL), followed by K2-
CO3 (0.75 mmol). The reaction mixture was degassed for 10 min
with CO and then stirred at 50 °C under a balloon pressure of
CO for 12 h. The reaction mixture was cooled, filtered through
a pad of silica gel, and then washed with EtOAc. The filtrate
was concentrated, and the residue was purified by flash chro-
matography (8/1 toluene/EtOAc) to give 8 in 40% yield and 6a
in 27% yield.
1
Com p ou n d 14: 91% yield as a white solid; H NMR δ 7.83
(d, J ) 8.0 Hz, 2H), 7.70 (d, J ) 16.0 Hz, 1H), 7.68 (m, 2H), 7.50
(t, J ) 7.5 Hz, 1H), 7.28-7.36 (m, 6H), 7.04 (s, 1H), 6.39 (d, J )
16.0 Hz, 1H), 4.10 (s, 3H), 3.81 (s, 3H); 13C NMR δ 191.7, 167.2,
158.4, 145.3, 145.0, 144.3, 137.3, 133.2, 131.3, 130.3, 129.8, 129.6,
128.8, 128.3, 128.2, 117.1, 116.1, 114.6, 106.1, 56.1, 51.5; HRMS
(ES) [C26H20O5], m/z (M+ + 1) calcd 413.1389, found 413.1401.
1
Com p ou n d 15: 61% yield as a white solid; H NMR δ 7.87
(s, 4H), 7.72 (d, J ) 15.5 Hz, 1H), 7.63 (d, J ) 7.0 Hz, 2H), 7.39
(s, 1H), 7.26-7.33 (m, 3H), 7.07 (s, 1H), 6.41 (d, J ) 15.5 Hz,
1H), 4.10 (s, 3H), 3.81 (s, 3H), 2.60 (s, 3H); 13C NMR δ 197.2,
190.9, 167.2, 159.4, 145.4, 144.9, 144.5, 140.8, 139.9, 131.6, 130.5,
130.2, 129.9, 129.8, 128.6, 128.3, 128.1, 117.4, 115.9, 114.6, 106.3,
56.1, 51.6, 26.7; HRMS (ES) [C28H23O6], m/z (M++1) calcd
455.1495, found: 455.1505.
1
Com p ou n d 16: 45% yield as a white solid; H NMR δ 7.88
(d, J ) 8.0 Hz, 2H), 7.73 (d, J ) 16.0 Hz, 1H), 7.57 (m, 4H), 7.45
(s, 1H), 7.26-7.34 (m, 3H), 7.08 (s, 1H), 6.43 (d, J ) 16.0 Hz,
1H), 4.10 (s, 3H), 3.82 (s, 3H); 13C NMR δ 190.5, 167.2, 159.7,
145.4, 144.8, 144.5, 140.3, 131.8, 130.2, 129.8, 128.7, 128.5, 128.4,
128.3, 128.2, 125.3, 125.2, 117.4, 115.7, 114.5, 106.4, 56.1, 51.6;
HRMS (ES) [C27H19F3O5], m/z (M+ + 1) calcd 481.1263, found
481.1238.
1
Com p ou n d 8: H NMR δ 7.78 (d, J ) 8.5 Hz, 2H), 7.73 (m,
2H), 7.59 (d, J ) 8.0 Hz, 1H), 7.50 (d, J ) 7.0 Hz, 1H), 7.36 (m,
1H), 7.32-7.34 (m, 3H), 7.25 (t, J ) 7.0 Hz, 1H), 6.84 (d, J ) 8.5
Hz, 1H), 3.84 (s, 3H); 13C NMR δ 191.2, 164.1, 156.5, 154.0, 132.6,
130.8, 129.0, 128.7, 128.3, 125.5, 123.9, 121.6, 116.6, 114.0, 55.7;
HRMS (EI) [C22H16O3], m/z (M+) calcd 328.1100, found 328.1093.
Gen er a l P r oced u r e for Syn th esis of 2-Su bstitu ted -3-
a r oyl-ben zo[b]fu r a n s. To a mixture of o-alkynylphenol (1
mmol), aromatic iodide (2 mmol), K2CO3 (5 mmol), and Pd(PPh3)4
(0.05 mmol) in a dry round-bottom flask (25 mL) was added dry
acetonitrile (10 mL) by cannulation. The reaction mixture was
degassed for 10 min with CO and then stirred at 45 °C under a
CO balloon for 5 h. The reaction mixture was cooled, filtered
through a pad of silica gel, and then washed with EtOAc. The
filtrate was concentrated, and the residue was purified by flash
chromatography to give the pure product.
1
Com p ou n d 17: 68% yield as a white solid; H NMR δ 7.78
(m, 2H), 7.72 (d, J ) 16.0 Hz, 1H), 7.68 (dd, J ) 4.0, 1.0 Hz,
1H), 7.45 (dd, J ) 4.0, 1.0 Hz, 1H), 7.39 (s, 1H), 7.35-7.39 (m,
3H), 7.04 (s, 1H), 6.96 (dd, J ) 4.0 Hz, 1H), 6.41 (d, J ) 16.0 Hz,
1H), 4.09 (s, 3H), 3.81 (s, 3H); 13C NMR δ 183.2, 167.2, 157.1,
145.3, 144.9, 144.3, 143.9, 135.1, 135.0, 131.3, 130.1, 129.9, 128.8,
128.4, 128.1, 128.0, 117.2, 116.3, 114.2, 106.2, 56.1, 51.5; HRMS
(ES) [C24H18O5S], m/z (M+ + 1) calcd 419.0953, found 419.0966.
Ack n ow led gm en t. We thank Professors Stuart L.
Schreiber, Timothy J . Mitchison, and Rebecca Ward for
their invaluable advice during the course of this re-
search. Financial support from NIH (Grant 1PO1
CA78048, Merck & Co. (Grant MCI97MITC804), and
Merck KGaA is gratefully acknowledged.
1
Com p ou n d 10: 86% yield as a white solid; H NMR δ 7.87
(d, J ) 9.0 Hz, 2H), 7.73-7.74 (m, 2H), 7.70 (d, J ) 16.0 Hz,
1H), 7.33-7.34 (m, 3H), 7.26 (s, 1H), 7.04 (s, 1H), 6.85 (d, J )
9.0 Hz, 2H), 6.39 (d, J ) 16.0 Hz, 1H), 4.10 (s, 3H), 3.85 (s, 3H),
3.81 (s, 3H); 13C NMR δ 190.3, 167.3, 163.9, 157.0, 145.3, 145.0,
144.3, 132.2, 131.1, 130.6, 130.1, 129.7, 128.9, 128.4, 128.0, 117.0,
116.4, 114.5, 113.7, 106.1, 56.2, 55.5, 51.3; HRMS(EI) [C27H22O6],
m/z (M+) calcd 442.1416, found: 442.1407.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and 1H and 13C NMR spectra for all new compounds
This material is available free of charge via the Internet at
http://pubs.acs.org.
Com p ou n d 11a : 70% yield as a white solid; 1H NMR δ 7.87
(d, J ) 9.0 Hz, 2H), 7.36-7.42 (m, 6H), 7.31 (d, J ) 7.0 Hz, 1H),
J O010839C