D. W. Price, Jr. et al. / Tetrahedron 59 (2003) 2497–2518
2515
acid methyl ester (40)22 (1.93 g, 12.03 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (0.160 g, 0.229 mmol),
copper(I) iodide (0.087 g, 0.46 mmol), DIEA (4.0 mL,
22.9 mmol), and THF (15 mL) were used following the
general procedure for couplings. The tube was capped and
stirred at room temperature for 1 h. Normal workup using
Et2O instead of CH2Cl2 afforded the desired product with no
need for further purification (4.37 g, 100% yield): mp 152–
1548C (decomp.). IR (KBr) 3078.2, 2955.3, 2217.9, 1716.5,
1602.4, 1540.2, 1434.0, 1357.7, 1278.5, 1105.5, 1015.5,
C24H15NO3S: 397.077266. Found: 397.076587 (error¼1.7
ppm).
7.5.46. 1-Oxy-2-phenyl-6-phenylethynyl-indol-3-one
(44). 2-Nitro-1,4-bis-phenylethynyl-benzene (26) (0.100 g,
0.31 mmol) and pyridine (6 mL) were placed in a 25 mL
round bottom flask. The solution was heated to reflux for
24 h. Hexanes were added and the solvents removed.
Column chromatography (silica gel using CH2Cl2 as eluent;
Rf¼0.84) afforded the product as an orange solid (0.081 g,
81% yield): mp 159–1708C. IR (KBr) 3057.8, 2212.8,
1717.2, 1525.3, 1384.2, 1314.0, 887.1, 838.8, 779.5, 751.8,
686.2, 500.6 cm21. 1H NMR (500 MHz, CDCl3) d 8.64 (m,
2H), 7.79 (m, 1H), 7.66 (dd, J¼7.5, 1.2 Hz, 1H), 7.60 (d,
J¼7.6 Hz, 1H), 7.56 (m, 2H), 7.49 (m, 3H), 7.38 (m, 3H).
13C NMR (100 MHz, CDCl3) d 186.4, 148.3, 134.6, 133.3,
132.3, 131.4, 130.8, 129.8, 129.0, 129.0, 128.3, 126.2, 122.5,
122.2, 122.0, 117.4, 95.1, 88.5. HRMS calcd for C22H13NO2:
323.094629. Found: 323.094450 (error¼0.55 ppm).
833.8, 757.3, 688.4, 517.8 cm21 1H NMR (400 MHz,
.
CDCl3) d 8.21 (dd, J¼1.5, 0.4 Hz, 1H), 8.03 (dt, J¼8.6,
1.7 Hz, 2H), 7.70 (dd, J¼8.1, 1.5 Hz, 1H), 7.66 (d,
J¼7.9 Hz, 1H), 7.63 (dt, J¼8.6, 1.7 Hz, 2H), 7.54 (m,
2H), 7.37 (m, 3H), 3.91 (s, 3H). 13C NMR (100 MHz,
CDCl3) d 166.8, 149.9, 135.8, 135.0, 132.4, 132.2, 130.9,
130.0, 129.7, 129.0, 128.1, 127.2, 125.1, 122.4, 117.8, 98.0,
94.4, 87.8, 87.2, 52.7. HRMS calcd for C24H15NO4:
381.100108. Found: 381.099938 (error¼0.45 ppm).
7.5.44. 4-(2-Nitro-4-phenylethynyl-phenylethynyl)-
benzoic acid (42). 4-(2-Nitro-4-phenylethynyl-phenyl-
ethynyl)-benzoic acid methyl ester (41) (2.0 g,
5.24 mmol), lithium hydroxide monohydrate (1.1 g,
26.2 mmol), MeOH (130 mL), water (45 mL), CH2Cl2
(100 mL), and THF (60 mL) were added to a 500 mL
round bottom flask and stirred at ambient temperature for
2 d. The suspension was poured into water and the pH
adjusted to 4 with 3N HCl. Hexanes were added to ensure
precipitation of all organic components and the solid was
filtered to afford the desired product as a yellow solid
(1.66 g, 86% yield): mp 234–2508C (decomp.). IR (KBr)
2817.1, 2653.2, 2530.3, 2207.7, 1683.5, 1601.5, 1541.6,
1521.9, 1421.3, 1340.6, 1314.0, 1293.0, 840.4, 758.6,
7.5.47. 5-Bromo-2-(trimethylsilylethynyl)pyridine (46).
To a large screw cap tube equipped with a stir bar was added
2,5-dibromopyridine (45) (2.37 g, 10.0 mmol), bis(tri-
phenylphosphine)palladium(II)
dichloride
(0.35 g,
0.50 mmol), copper(I) iodide (0.19 g, 1.0 mmol) and
triphenylphosphine (0.52 g, 2.0 mmol). The atmosphere
was replaced with nitrogen and THF (40 mL), triethylamine
(4.35 mL, 40.0 mmol), THF (10 mL), and TMSA (1.4 mL,
10 mmol) were added. The reaction mixture turned dark
brown in color as the reaction was heated at 658C for 2 d.
The reaction was subjected to the aqueous work up
procedure listed above. The reaction afforded 2.25 g of an
inseparable mixture of product and starting material. NMR
showed the mixture to be 54% product. 1H NMR (400 MHz,
CDCl3) d 8.61 (dd, J¼2.4, 0.73 Hz, 1H), 7.76 (dd, J¼8.4,
2.4 Hz, 1H), 7.32 (dd, J¼8.2, 0.73 Hz, 1H).
1
692.0 cm21. H NMR (400 MHz, DMSO) d 8.34 (m, 1H),
8.02 (m, 2H), 7.96 (dd, J¼8.1, 1.5 Hz, 1H), 7.93 (d,
J¼8.0 Hz, 1H), 7.71 (m, 2H), 7.64 (m, 2H), 7.48 (m, 3H).
13C NMR (125 MHz, DMSO) d 167.5, 150.2, 136.7, 135.9,
132.8, 132.6, 132.4, 130.6, 129.8, 128.3, 126.4, 124.7,
122.1, 117.1, 97.8, 94.5, 87.8, 87.7. HRMS calcd for
C23H13NO4: 367.084458. Found: 367.084044 (error¼1.1
ppm).
7.5.48. 2-(Phenylethynyl)-5-(trimethylsilylethynyl)pyri-
dine (47). To a 250 mL round bottom flask equipped with
a stir bar were added 46 (2.25 g, 9.50 mmol), bis(tri-
phenylphosphine)palladium(II)
dichloride
(0.53 g,
0.76 mmol), copper(I) iodide (0.29 g, 1.5 mmol) and
triphenylphosphine (0.80 g, 3.0 mmol). The atmosphere
was evacuated and replaced with nitrogen and THF
(50 mL), triethylamine (4.13 mL, 38.0 mmol), and phenyl-
acetylene (3.13 mL, 28.5 mmol) were added. The reaction
was heated to reflux and maintained for 2 d. The
triethylamine salts that formed during the reaction were
filtered off and the reaction was washed with aqueous
ammonium chloride (3£). The remaining solvent was
removed in vacuo to yield 272 mg (19%) of desired product
over 2 steps: mp 98–1008C. IR (KBr) 2959.5, 2157.9,
1492.3, 1463.6, 1384.0, 1247.7, 1019.9, 844.4, 754.8,
7.5.45. Thioacetic acid S-[4-(3-oxo-1-oxy-6-phenyl-
ethynyl-3H-indol-2-yl)-phenyl] ester (43). To a 10 mL
round bottom flask was added thioacetic acid S-[4-(2-
nitro-4-phenylethynyl-phenylethynyl)-phenyl] ester (17)
(0.100 g, 0.25 mmol). Air was removed and N2 backfilled
(3£). THF (5 mL) was added followed by TBAF (1 drop of
a 1.0 M solution). The solution was stirred for 15 min at
room temperature before 3N HCl (,1 mL) was added. The
product was extracted with CH2Cl2. Column chromato-
graphy (silica gel using 2:1 CH2Cl2/hexanes; Rf¼0.48)
afforded the product as a bright orange solid (0.073 g,
73% yield): mp 202–2058C. IR (KBr) 3093.6, 3047.5,
2212.8, 1714.3, 1699.8, 1634.1, 1588.9, 1517.0, 1380.5,
690.3 cm21 1H NMR (400 MHz, CDCl3) d 8.70 (d,
.
J¼1.3 Hz, 1H), 7.74 (dd, J¼6.0, 2.6 Hz, 1H), 7.53 (m,
2H), 7.43 (d, J¼8.0 Hz, 1H), 7.36 (m, 3H). 13C NMR
(75 MHz, CDCl3) d 152.3, 141.5, 138.4, 131.7, 131.6,
131.5, 129.4, 129.3, 129.0, 128.5, 128.3, 128.2, 128.1,
127.9, 126.6, 122.3, 119.8, 103.5, 97.0, 94.5, 85.9, 20.1.
HRMS calcd for C19H17NSi: 275.1130. Found: 275.1126.
1181.0, 1126.0, 835.6, 743.1, 692.0, 630.4 cm21 1H
.
NMR (400 MHz, CDCl3) d 8.73 (dt, J¼8.8, 1.9 Hz, 2H),
7.80 (m, 1H), 7.67 (dd, J¼7.5, 1.2 Hz, 1H), 7.61 (m, 1H),
7.55 (m, 4H), 7.38 (m, 3H), 2.44 (s, 3H). 13C NMR
(100 MHz, CDCl3) d 193.4, 186.2, 148.3, 134.8, 134.6,
132.3, 131.5, 131.0, 129.8, 129.0, 128.6, 127.0, 122.4,
122.2, 122.1, 117.5, 95.3, 88.4, 53.8, 30.8. HRMS calcd for
7.5.49. 2-(Phenylethynyl)-5-(ethynyl)pyridine (48). To a
100 mL round bottom flask equipped with a magnetic stir