J.-Y. Legros et al. / Tetrahedron 57 (2001) 2507±2514
2513
in cross-coupling although some homocoupling of the
substrate was observed.
4.1.3. 4-Acetyl-7-chloroquinoline 12. Mp 75±768C. IR
1
(KBr) nmax: 1690 cm21. H NMR: 2.74 (3H, s), 7.57 (1H,
dd, J9 and 2 Hz), 7.63 (1H, d, J4 Hz), 8.13 (1H, d, J
2 Hz), 8.47 (1H, d, J9 Hz), 9.03 (1H, d, J4 Hz). 13C
NMR: 29.8, 120.2, 122.1, 127.1, 128.8, 129.3, 136.0,
142.1, 149.7, 150.0, 200.6. HRMS calculated for
C11H8ClNO: 205.029442. Found: 205.0290.
4. Experimental
4.1. General
1H and 13C NMR were recorded on a Bruker AC-250 MHz
spectrometer in CDCl3 with tetramethylsilane as an internal
standard.
4.1.4. 1-Acetyl-3-chloroisoquinoline 14. Mp 83±858C. IR
1
(KBr) nmax: 1690 cm21. H NMR 2.83 (3H, s), 7.64±7.77
(3H, m), 7.86 (1H, s), 8.92 (1H, dd, J8 and 1.5 Hz). 13C
NMR 28.4, 124.1, 124.6, 126.3, 127.2, 129.5, 131.3, 139.5,
143.7, 152.7, 201.1. HRMS calculated for C11H8ClNO:
205.029442. Found: 205.0295.
All reactions involving palladium catalysis were carried out
using Schlenk techniques under an argon atmosphere. Tetra-
hydrofuran (THF) was distilled under argon from sodium
benzophenone ketyl immediatly before use. Dioxane,
toluene and N,N-dimethylformamide (DMF) were dried
over CaH2 and distilled prior to use.
4.1.5. Palladium-catalyzed Negishi cross-coupling reac-
tion with 1-ethoxyvinylzinc chloride 8b. A typical pro-
cedure is as follows (Table 4, entry 4): a 3 mL solution of
ethyl vinyl ether (0.3 mL, 3 mmol) in THF was cooled to
2788C under argon and 1.3 mL of a 1.5 M commercial
solution of t-butyllithium in pentane (2 mmol) was added
dropwise. The reaction mixture was warmed to 08C, stirred
for 1 h, then cooled back to 2788C and a 3 mL solution of
anhydrous zinc dichloride (272 mg, 2 mmol) in THF was
added. The resulting mixture was warmed to room tempera-
ture and stirred for 0.5 h.
Pd(dba)2 (dba denotes dibenzylideneacetone) was prepared
according to a reported procedure.35 The following
materials were obtained from commercial sources and
used as purchased: Pd(OAc)2, PdCl2(PPh3)2, 2-chloroquino-
line 1c, 3-bromoquinoline 2b, 4-chloroquinoline 3c,
4-hydroxyquinoline 3d0, 8-hydroxyquinoline 4d0, 1-hydroxy-
isoquinoline 5d0, 3-hydroxyisoquinoline 6d0, 4-bromoiso-
quinoline 7b, 4,7-dichloroquinoline 9, 1,3-dichloro-
isoquinoline 11. 2,4-Dichloroquinoline 10,36 (1-ethoxyvinyl)-
tri(n-butyl)stannane 8a,25 and tri¯ates 3d±6d23 were
prepared as reported in the literature.
A THF (3 mL) solution of Pd(dba)2 (23 mg, 0.04 mmol),
PPh3 (21 mg, 0.08 mmol), 2-bromoquinoline 2b (208 mg,
1 mmol) was stirred at room temperature under argon for
0.25 h and then added to the previously prepared organozinc
8b solution. The resulting reaction mixture was stirred at
708C for 48 h, cooled to room temperature, then 10 mL of
1 M HCl were added. After 24 h stirring, the reaction
mixture was neutralized with 1 M NaOH and extracted
with 3£10 mL of diethyl ether. The combined ethereal
phases were dried (MgSO4) and concentrated. The crude
product was puri®ed by ¯ash chromatography (silica,
heptane/ethyl acetate 8:2) to give 2a (111 mg, 0.65 mmol,
65%).
4.1.1. Palladium-catalyzed Stille cross-coupling reac-
tions with (1-ethoxyvinyl)tri(n-butyl)stannane 8a. A typi-
cal procedure for heteroaryl halides is as follows (Table 1,
entry 2): a toluene (3 mL) solution of Pd(dba)2 (23 mg,
0.04 mmol), PPh3 (21 mg, 0.08 mmol) and 2-bromoquino-
line 2b (208 mg, 1 mmol) was stirred at room temperature
under argon for 0.25 h. (1-Ethoxyvinyl)tri(n-butyl)stannane
8a (363 mg, 1 mmol) in toluene (2 mL) was added and the
resulting reaction mixture was stirred at 1108C for 1 h,
cooled to room temperature, then 10 mL of 1 M HCl were
added. After 24 h stirring, the reaction mixture was neutra-
lized with 1 M NaOH and extracted with 3£10 mL of
diethyl ether. The combined ethereal phases were dried
(MgSO4) and concentrated. The crude product was puri®ed
by ¯ash chromatography (silica, heptane/ethyl acetate 8:2)
to give 2a (150 mg, 0.88 mmol, 88%).
4.1.6. Palladium-catalyzed cross-coupling with tri-
(1-ethoxyvinyl)indium 8c. A typical procedure is as
follows (Table 4, entry 7): a 3 mL solution of ethyl vinyl
ether (0.3 mL, 3 mmol) in THF was cooled to 2788C under
argon and 1.3 mL of a 1.5 M commercial solution of t-butyl-
lithium in pentane (2 mmol) was added dropwise. The reac-
tion mixture was warmed to 08C, stirred for 1 h, then cooled
back to 2788C and a 3 mL solution of anhydrous indium
trichloride (160 mg, 0.7 mmol) in THF was added. The
resulting mixture was warmed to room temperature and
stirred for 0.5 h.
The procedure for heteroaryltri¯ates was modi®ed as
follows: LiCl (127 mg, 3 mmol) was added to the catalyst
Ð substrate solution and dioxane was substituted for
toluene.
Spectral data of compounds 1a±3a,16 5a±7a,16 and 1337
were in satisfactory agreement with the reported values.
A THF (3 mL) solution of Pd(dba)2 (23 mg, 0.04 mmol),
PPh3 (21 mg, 0.08 mmol), 2-bromoquinoline 2b (208 mg,
1 mmol) was stirred at room temperature under argon for
0.25 h and then added to the previously prepared organo-
indium 8c solution. The resulting reaction mixture was
stirred at 708C for 48 h, cooled to room temperature, then
10 mL of 1 M HCl were added. After 24 h stirring, the reac-
tion mixture was neutralized with 1 M NaOH and extracted
with 3£10 mL of diethyl ether. The combined ethereal
phases were dried (MgSO4) and concentrated. The crude
4.1.2. 8-Acetylquinoline 4a. Mp 428C (lit:8 42±43.58C). IR
1
(KBr) nmax: 1683 cm21. H NMR: 2.92 (3H, s), 7.44 (1H,
dd, J8 and 4 Hz), 7.56 (1H, t, J8 Hz), 7.90±7.94 (2H,
m), 8.18 (1H, dd, J8 and 2 Hz), 8.96 (1H, dd, J4 and
2 Hz). 13C NMR 32.6, 121.3, 125.9, 128.2, 129.1, 131.2,
136.2, 139.5, 145.4, 150.3, 203.8. HRMS calculated for
C11H9NO: 171.068420. Found: 171.0690.