3804
S.-X. Sun et al. / Tetrahedron 70 (2014) 3798e3806
diluted with water (15 mL) and ether (100 mL). The layers were
separated and the organic phase was washed with abundant water
before being dried over Na2SO4, filtered, and the solvent was re-
moved under reduced pressure to afford compound B as a yellow
oil.33
(73.53), H (3.97); Found: C (73.43), H (3.99); HRMS (ESI) m/z calcd for
C
14H9ClNaO [MþNa]þ 251.0234, found: 251.0236. The spectroscopic
data match the previously reported in the literature.35
4.2.9. 2-((4-Bromophenyl)ethynyl)phenol
(203 mg, 84%); 1H NMR (400 MHz)
: 7.53e7.48 (m, 2H), 7.43e7.36
(m, 3H), 7.31e7.25 (m, 1H), 6.98 (d, J¼8.4 Hz, 1H), 6.92 (t, J¼7.6 Hz,
1H), 5.76 (s, 1H); 13C NMR (100 MHz)
: 156.5, 133.8, 133.0, 131.8,
(1f). Yellow
solid
d
4.2.2. Sonagashira reaction (SP2). Pd(PPh3)2Cl2 (5 mol %) and CuI
(5 mol %) were added to a solution of alkyne (1.1 equiv) and com-
pound B (1.0 equiv) in THF and triethylamine mixture solution. The
resulting mixture was stirred at 50 ꢀC until the reaction was com-
plete as determined by TLC. On completion, the mixture was
allowed to cool to room temperature. Removal of solvent under
reduced pressure afforded a residue, which was purified by flash
chromatography in ethyl acetate/petroleum ether to afford the
compound C.
d
131.7, 130.8, 123.1, 121.4, 120.5, 114.9, 109.3, 95.2, 84.3; MS (EI) m/z
(%): 274 (92), 272 (Mþ, 93), 165 (100). The spectroscopic data match
the previously reported in the literature.38
4.2.10. 2-(m-Tolylethynyl)phenol (1g). Colorless oil (264 mg, 90%);
1H NMR (400 MHz)
d
: 7.41 (dd, 1J¼8.0 Hz, 2J¼1.6 Hz, 1H), 7.37e7.33
(m, 2H), 7.29e7.24 (m, 2H), 7.18 (d, J¼7.6 Hz, 1H), 6.97 (d, J¼8.0 Hz,
1H), 6.91 (t, 1J¼7.6 Hz, 2J¼1.2 Hz, 1H) 5.84 (s, 1H), 2.36 (s, 3H); 13C
4.2.3. MOM deprotection (SP3). HCl (6 M) was added to a solution
of the MOM protected compound C in CH3OH solution and the
mixture was stirred at reflux temperature until deprotection was
complete. Dilution with water and ethylether and extraction of the
aqueous layer with ethylether was followed by washing of the
combined organic phases with brine, drying over Na2SO4, and re-
moving the solvent under reduced pressure to afford a residue,
which can be purified by flash chromatography in ethyl acetate/
petroleum to afford the reactants.17f
NMR (100 MHz) d: 156.5, 138.2, 132.2, 131.6, 130.4, 129.7, 128.7, 128.4,
122.2, 120.4, 114.7, 109.7, 96.6, 82.6; MS (EI) m/z (%): 208 (Mþ, 100).
HRMS (c ESI) m/z calcd for C15H12O [M]þ 208.0883, found: 208.0896.
4.2.11. 2-((3-Fluorophenyl)ethynyl)phenol (1h). Yellow solid (277 mg,
91%); 1H NMR (400 MHz)
d
: 7.42 (dd, 1J¼7.6 Hz, 2J¼1.6 Hz, 1H),
7.36e7.27 (m, 3H), 7.25e7.22 (m, 1H), 7.12e7.06 (m, 1H), 6.99 (dd,
1J¼8.4 Hz, 2J¼0.4 Hz, 1H), 6.93 (dd, 1J¼7.6 Hz, 2J¼0.8 Hz, 1H), 5.75 (s,
1H); 13C NMR (100 MHz)
d: 163.6, 161.2, 156.6, 131.8, 130.8, 130.2,
The following compounds were prepared by this method:
130.1, 127.5, 127.4, 124.3, 124.2, 120.5, 118.5, 118.3, 116.3, 116.1, 114.9,
109.1, 95.0, 94.9, 84.0; MS (EI) m/z (%): 212 (Mþ, 100). The spectro-
scopic data match the previously reported in the literature.17j
4.2.4. 2-(Phenylethynyl)phenol (1a). Yellow solid (2.59 g, 97%); 1H
NMR (400 MHz, CDCl3):
d
: 7.56e7.53 (m, 2H), 7.43 (dd, 1J¼8.0 Hz,
2J¼1.6 Hz, 1H), 7.39e7.37 (m, 3H), 7.30e7.27 (m, 1H), 6.98 (d,
4.2.12. 2-((3-Chlorophenyl)ethynyl)phenol
(1i). Yellow
solid
J¼8.4 Hz,1H), 6.92 (t, J¼7.6 Hz,1H), 5.83 (s,1H); 13C NMR (100 MHz)
(205 mg, 90%), mp 96e98 ꢀC; 1H NMR (400 MHz)
d
: 7.54e7.52 (m,
d
: 156.5, 131.6, 130.5, 128.8, 128.5, 122.4, 120.4, 114.7, 109.6, 96.4,
1H), 7.45e7.40 (m, 2H), 7.36e7.26 (m, 3H), 6.98 (d, J¼8.4 Hz, 1H),
83.0; MS (EI) m/z (%): 194 (Mþ, 100). The spectroscopic data match
6.92 (t, J¼8.0 Hz, 1H), 5.74 (s, 1H); 13C NMR (100 MHz)
d: 156.6,
the previously reported in the literature.34
134.4, 131.8, 131.4, 130.9, 129.7, 129.6, 124.1, 120.5, 114.9, 109.1, 94.8,
84.3; MS (EI) m/z (%): 230 (32), 228 (Mþ, 100); Anal. Calcd for
4.2.5. 2-(Thiophen-2-ylethynyl)phenol (1b). Yellow solid (801 mg,
C
14H9OCl: C (73.53), H (3.97); Found: C (73.55), H (3.98). HRMS (c
85%); 1H NMR (400 MHz)
d
: 7.41 (d, J¼7.6 Hz, 1H), 7.33e7.25 (m,
3H), 7.03 (t, J¼4.4 Hz, 1H), 6.98 (d, J¼8.4 Hz, 1H), 6.91 (t, J¼7.6 Hz,
1H), 5.77 (s, 1H); 13C NMR (100 MHz)
: 156.5, 132.5, 131.7, 130.7,
ESI) m/z calcd for C14H19OCl [M]þ 228.0336, found: 228.0350.
d
4.2.13. 2-((3-Bromophenyl)ethynyl)phenol
(1j). Yellow
solid
128.0, 127.2, 122.3, 120.5, 114.9, 109.3, 89.3, 86.7; MS (EI) m/z (%):
200 (Mþ, 100). The spectroscopic data match the previously re-
ported in the literature.35
(193 mg, 87%); 1H NMR (400 MHz)
d: 7.71e7.69 (m, 1H), 7.54e7.45
(m, 2H), 7.41 (dd, 1J¼7.6 Hz, 2J¼1.6 Hz, 1H), 7.32e7.26 (m, 1H),
7.25e7.22 (m, 1H), 6.98 (d, J¼7.6 Hz, 1H), 6.92 (t, J¼7.6 Hz, 1H), 5.73
(s, 1H); 13C NMR (100 MHz)
d: 156.6, 134.3, 131.9, 131.8, 130.9, 130.1,
4.2.6. 2-(p-Tolylethynyl)phenol (1c). Yellow solid (410 mg, 91%); 1H
129.9, 124.4, 122.3, 120.5, 114.9, 109.1, 94.6, 84.5; MS (EI) m/z (%):
274 (88), 272 (Mþ, 92), 165 (100). The spectroscopic data match the
previously reported in the literature.26
NMR (400 MHz)
J¼8.0 Hz, 2H), 6.98 (d, J¼7.6 Hz, 1H), 6.91 (t, J¼7.6 Hz, 1H), 5.84 (s,
1H), 2.39 (s, 3H); 13C NMR (100 MHz)
: 156.5, 139.2, 131.7, 131.6,
d: 7.45e7.40 (m, 3H), 7.29e7.24 (m, 1H), 7.18 (d,
d
130.4, 129.3, 120.5, 119.4, 114.7, 109.9, 96.7, 82.4, 21.6; MS (EI) m/z
(%): 208 (Mþ, 100), 207 (51). The spectroscopic data match the
previously reported in the literature.36
4.2.14. 2-(Hex-1-ynyl)phenol (1k). Colorless oil (176 mg, 70%); 1H
NMR (400 MHz)
d
: 7.31 (dd, 1J¼7.6 Hz, 2J¼1.6 Hz, 1H), 7.19e7.16 (m,
1H), 6.92 (d, J¼8.4 Hz, 1H), 6.86e6.81 (m, 1H), 5.81 (s, 1H), 2.48 (t,
J¼6.8 Hz, 2H), 1.65e1.58 (m, 2H), 1.53e1.43 (m, 2H), 0.96 (t,
4.2.7. 2-((4-Fluorophenyl)ethynyl)phenol
(1d). Yellow
solid
J¼7.2 Hz, 3H); 13C NMR (100 MHz)
d: 156.5, 131.4, 129.6, 120.1, 114.3,
(312 mg, 90%); 1H NMR (400 MHz)
d
: 7.55e7.51 (m, 2H), 7.41 (dd,
110.2, 98.0, 74.5, 30.8, 22.0,19.3,13.6; MS (EI) m/z (%): 174 (Mþ,100),
131 (55). The spectroscopic data match the previously reported in
the literature.35
1J¼7.6 Hz, 2J¼1.6 Hz, 1H), 7.30e7.26 (m, 1H), 7.08 (t, J¼8.4 Hz, 2H),
6.98 (d, J¼8.0 Hz, 1H), 6.91 (t, J¼8.4 Hz, 1H), 5.77 (s, 1H); 13C NMR
(100 MHz) d: 164.1, 161.6, 156.5, 133.6, 133.5, 131.7, 130.6, 120.5,
118.5, 118.4, 116.0, 115.7, 114.8, 109.4, 95.2, 82.8; MS (EI) m/z (%): 212
(Mþ, 100). The spectroscopic data match the previously reported in
the literature.37
4.2.15. 4-Methyl-2-(phenylethynyl)phenol
(1l). Yellow
solid
(211 mg, 87%); 1H NMR (400 MHz)
d: 7.53e7.51 (m, 2H), 7.38e7.35
(m, 3H), 7.26e7.23 (m, 1H), 7.07 (dd, 1J¼7.6 Hz, 2J¼2.0 Hz, 1H), 6.87
(d, J¼8.4 Hz, 1H), 5.66 (s, 1H), 2.28 (s, 3H); 13C NMR (100 MHz)
d:
4.2.8. 2-((4-Chlorophenyl)ethynyl)phenol (1e). Yellow solid (211 mg,
154.4, 131.7, 131.6, 131.3, 129.6, 128.7, 128.5, 122.5, 114.5, 109.2, 96.0,
83.3, 20.3; MS (EI) m/z (%): 208 (Mþ, 100), 207 (67). The spectro-
scopic data match the previously reported in the literature.35
1
88%); H NMR (400 MHz)
d
: 7.49e7.45 (m, 2H), 7.42 (dd, 1J¼7.6 Hz,
2J¼1.6 Hz, 1H), 7.35 (d, J¼8.8 Hz, 2H), 7.31e7.26 (m, 1H), 6.98 (d,
J¼8.0 Hz, 1H), 6.92 (t, J¼7.6 Hz, 1H), 5.75 (s, 1H); 13C NMR (100 MHz)
d
: 156.5,134.9,132.8,131.7,130.7,128.9,120.9,120.5,114.8,109.3, 95.1,
4.2.16. 4-Methyl-2-(p-tolylethynyl)phenol
(1m). Yellow
solid
84.0; MS (EI) m/z (%): 228 (Mþ, 100); Anal. Calcd for C14H9OCl: C
(173 mg, 81%); 1H NMR (400 MHz)
d
: 7.42 (d, J¼8.0 Hz, 2H), 7.22 (s,