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F. Yang et al. / Tetrahedron 67 (2011) 2969e2973
3. Conclusion
4.2.4. (3-Phenylisoquinolin-4-yl)methanol (3d)7b. White solid, mp
177e178 ꢀC (lit. 175e176 ꢀC); 1H NMR (400 MHz, CDCl3):
5.08
d
In summary, we have accomplished the convenient and efficient
synthesis of isoquinolines by a tandem reaction of imination and
palladacycle-catalyzed iminoannulation of internal alkynes with
high regioselectivity. On the other hand, we also offered a facile
protocol for the synthesis of indoles via the catalytic annulation of
o-iodoaniline or o-bromoaniline with internal alkynes. Further in-
vestigations on the application of these synthetic methodologies
are currently underway in our laboratory.
(s, 2H), 7.43 (m, 1H), 7.48 (t, J¼6.8 Hz, 2H), 7.66 (m, 3H), 7.82
(t, J¼7.7 Hz, 2H), 8.03 (d, J¼8.1 Hz, 1H), 8.31 (d, J¼8.5 Hz, 1H), 9.26
(s, 1H); 13C NMR (100 MHz, CDCl3):
d 59.4, 123.9, 125.7, 127.0, 127.7,
128.1, 128.2, 128.3, 129.7, 131.1, 135.8, 140.1, 152.3, 152.8.
4.2.5. 4,6-Dimethyl-3-phenylisoquinoline (3e). White solid, mp
95e96 ꢀC; 1H NMR (400 MHz, CDCl3):
d 2.61 (s, 3H), 2.63 (s, 3H),
7.26 (s, 1H), 7.40e7.49 (m, 3H), 7.57e7.59 (d, 2H), 7.82 (s, 1H), 7.90
(d, J¼8.2 Hz, 1H), 9.14 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 15.5,
22.5, 122.6, 123.4, 125.6, 127.4, 128.0, 128.8, 129.8, 136.4, 140.7, 141.4,
149.7, 151.8; HRMS (positive ESI) calcd for C17H16N: 234.1283
(MþþH), found: 234.1279.
4. Experimental
4.1. General methods
4.2.6. 4-Phenyl-3-(p-tolyl)isoquinoline (3f) with 3-phenyl-4-(p-tolyl)
isoquinoline (3g) (1:1)3a. White solid, mp 93e100 ꢀC (3g lit.129 ꢀC);
All commercial materials were used without further purifica-
tion. 1H and 13C NMR spectra were recorded in CDCl3 solution on
a Bruker DPX-400 spectrometer. Melting points were measured
using a WC-1 microscopic apparatus and were uncorrected. GC
analysis was performed on Agilent 4890D gas chromatograph.
Mass spectra were measured on an LC-MSD-Trap-XCT instrument.
High-resolution mass spectra were obtained on a Waters Q-Tof
MicroTM spectrometer. Ethyl acetate and hexane (analytical grade)
were used for column chromatography without purification. The
other chemicals were obtained from commercial sources and used
as received unless otherwise noted.
1H NMR (400 MHz, CDCl3):
d
2.28 (s, 3H), 2.39 (s, 3H), 7.00e7.02 (m,
2H), 7.14e7.28 (m, 16H), 7.36e7.39 (m, 4H), 7.58e7.60 (m, 2H),
8.02e8.04 (m, 1H), 9.36 (s, 2H); 13C NMR (100 MHz, CDCl3):
21.1,
d
21.3, 125.5, 125.6, 126.7, 126.8, 126.9, 127.2, 127.5, 127.6, 128.3, 128.4,
130.1,130.2,130.4, 131.0, 131.2, 136.7, 137.4,150.5, 151.5,151.7; HRMS
(positive ESI) calcd for C22H18N: 296.1439 (MþþH), found: 296.1437.
4.2.7. 7,8-Diphenyl-[1,3]dioxolo[4,5-g]isoquinoline
solid, mp 231e233 ꢀC (lit. 234e235 ꢀC); 1H NMR (400 MHz, CDCl3):
6.04 (s, 2H), 7.00 (s, 1H), 7.17e7.34 (m, 1H); 13C NMR (100 MHz,
CDCl3): 101.8, 102.1, 103.0, 124.9, 127.1, 127.5, 128.2, 130.1, 131.1,
(3h)7b. White
d
d
4.2. General procedure for synthesis of isoquinolines
134.5, 137.9, 140.9, 148.3, 149.5, 150.2, 151.4.
To a solution of o-halobenzaldehyde (0.25 mmol) in DMF (1 mL),
tert-butyl amine (0.75 mmol) was added. The resulting mixture was
stirred under a nitrogen atmosphere at room temperature for 12 h
(or 100 ꢀC for 4 h). After the haloaldehyde was consumed com-
pletely (monitored by TLC), alkynes (0.50 mmol), Na2CO3
(0.50 mmol), LiCl (0.25 mmol), palladacycle (1 mol %), and DMF
(1 mL) were added to the mixture. Then the vial was placed in
a preheated oil bath and heated at 100 ꢀC under stirring for 24 h.
After the reaction was complete (monitored by TLC), the mixture
was diluted with CH2Cl2 (10 mL), filtered through a pad of Celite,
and extracted with CH2Cl2. The combined organic phase was dried
over anhydrous Na2SO4, filtered, and evaporated under reduced
pressure. The residue was purified by flash chromatography on
silica gel (ethyl acetate/hexane) to afford the pure product.
4.2.8. 2,3-Diphenyl-1H-inden-1-one (4a)10. Red solid, mp 147e
149 ꢀC (lit. 152e153 ꢀC); 1H NMR (400 MHz, CDCl3):
d 7.15 (d,
J¼7.3 Hz, 1H), 7.25e7.28 (m, 6H), 7.37e7.42 (m, 6H), 7.59 (d,
J¼7.3 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 121.2, 122.9, 127.7,
128.0, 128.5, 128.7, 128.9, 129.2, 129.9, 130.7, 132.3, 132.7, 133.4,
145.1, 155.2, 196.5.
4.2.9. 2-Methyl-3-phenyl-1H-inden-1-one (4c)11. Orange solid, mp
80e82 ꢀC (lit. 83e84 ꢀC); 1H NMR (400 MHz, CDCl3):
d
1.93 (s, 3H,
C-2 methyl), 7.07 (d, J¼7.2 Hz, 1H), 7.17e7.54 (m, 3H), 7.49 (s, 5H);
13C NMR (100 MHz, CDCl3):
8.6, 120.4, 122.5, 128.0, 128.1, 128.7,
d
129.1, 131.0, 131.1, 132.7, 133.1, 145.7, 154.7, 198.3.
4.2.10. 6,7-Diphenyl-5H-indeno[5,6-d][1,3]dioxol-5-one
(4h). Purple solid, mp 157e158 ꢀC; 1H NMR (400 MHz, CDCl3):
4.2.1. 3,4-Diphenylisoquinoline (3a)7a. White solid, mp 168e169 ꢀC
d
6.02 (s, 2H), 6.65 (s, 1H), 7.09 (s, 1H), 7.22e7.26 (s, 5H), 7.32e7.35
(lit. 170 ꢀC); 1H NMR (400 MHz, CDCl3):
d
7.19e7.21 (m, 3H),
(m, 2H), 7.40 (m, 3H); 13C NMR (100 MHz, CDCl3):
d
102.1, 104.0,
7.24e7.26 (m, 2H), 7.35e7.38(m, 5H), 7.59e7.62 (m, 2H), 7.67 (dd,
J¼4.2 and 5.3 Hz, 1H), 8.04 (dd, J¼5.1 and 4.2 Hz, 1H), 9.37 (s, 1H);
105.3, 124.7, 127.5, 128.0, 128.4, 128.9, 129.3, 129.8, 130.8, 131.4,
132.7, 141.8, 147.7, 151.6, 153.7, 195.2; HRMS (positive ESI) calcd for
C22H14O3Na: 349.0841 [MþNa]þ, found: 349.0840.
13C NMR (100 MHz, CDCl3):
d 125.6, 126.9, 127.1, 127.3, 127.6, 127.6,
128.3, 130.2, 130.5, 130.6, 131.2, 135.9, 137.2, 140.8, 150.6, 151.7.
4.3. General procedure for synthesis of indole
4.2.2. 6-Methyl-3,4-diphenylisoquinoline (3b). White solid, mp
178e179 ꢀC; 1H NMR (400 MHz, CDCl3):
d
2.45 (s, 3H), 7.18e7.20 (m,
o-Halobenzaldehyde (0.25 mmol), diphenylacetylene (0.50 mmol),
palladacycle (1 mol %), additive (0.25 mmol), and K2CO3 (0.50 mmol)
were dissolved in DMF (1.50 mL) in a 10 mL vial under air and heated at
100 ꢀC for 24 h. After the reaction was complete (monitored by TLC),
the mixture was diluted with CH2Cl2 (10 mL), filtered through a pad of
Celite, and washed multiple times with CH2Cl2. The combined organic
layerwasdried overanhydrous Na2SO4, filtered, and evaporated under
reduced pressure and the residue was purified by flash chromatogra-
phy on silica gel (ethyl acetate/hexane) to afford the pure product.
3H), 7.23e7.25 (m, 3H), 7.34e7.37 (m, 5H), 7.42e7.45 (m, 2H), 7.96
(d, J¼8.2 Hz, 1H), 9.30 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 22.4,
124.4,125.8, 126.9,127.2,127.4,127.6, 128.2, 129.1,130.1, 130.2, 131.2,
136.1, 137.4, 140.9, 150.7, 151.3; HRMS (positive ESI) calcd for
C22H18N: 296.1439 (MþþH), found: 296.1440.
4.2.3. 4-Methyl-3-phenylisoquinoline (3c)7a. White solid, mp
101e102 ꢀC (lit. 103e104 ꢀC); 1H NMR (400 MHz, CDCl3):
d 2.66 (s,
3H), 7.24e7.26 (m, 2H), 7.35e7.38(m, 5H), 7.59e7.62 (m, 2H), 7.67
(dd, J¼4.2 and 5.3 Hz, 1H), 8.04 (dd, J¼5.1 and 4.2 Hz, 1H), 9.21 (s,
4.3.1. 2,3-Diphenyl-1H-indole (6a)12. White solid, mp 113e114 ꢀC
1H); 13C NMR (100 MHz, CDCl3):
d
15.5, 123.6, 124.0, 126.6, 127.2,
(lit. 120e121 ꢀC); 1H NMR (400 MHz, CDCl3):
d 7.44e7.15(m, 13H),
127.5, 128.1, 129.8, 130.4, 136.2, 141.3, 150.1, 151.8.
7.67 (d, J¼7.9 Hz, 1H), 8.21 (s, 1H); 13C NMR (100 MHz, CDCl3):