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Palladium-Catalysed Direct C H Coupling
FULL PAPER
was obtained as a white solid (44 mg, 60%). Analytical data are identical
to those previously reported.
(CDCl3, 300 MHz): d=1.41 (t, J=7.2 Hz, 3H), 3.03 (s, 6H), 4.41 (q, J=
7.2 Hz, 2H), 6.74 (d, J=9.0 Hz, 2H), 7.79 (s, 1H), 8.03 ppm (d, J=
9.0 Hz, 2H); 13C NMR (CDCl3, 75 MHz): d=14.3, 39.9, 60.9, 111.1,
113.8, 123.6, 129.6, 147.6, 151.3, 156.7, 162.3 ppm; IR (KBr): n˜ =3125,
2899, 1705, 1608, 1516, 1371, 1181, 1070, 1029, 944, 785, 641 cmÀ1; ele-
mental analysis calcd (%) for C14H16N2O3 (260.3): C 64.60, H 6.20, N
10.76; found: C 64.82, H 6.34, N 10.84.
Compound 3h: By following the above procedure with 3-bromoquinoline
(48 mL) and PtBu3·HBF4 (10.1 mg), compound 3h was obtained as a
white solid (43 mg, 48%). Analytical data are identical to those previous-
ly reported.
Compound 3i: By following the above procedure with 5-bromopyrimi-
dine (56 mg) and PtBu3·HBF4 (10.1 mg), compound 3i was obtained as a
Compound 5e: By following the above procedure with 2-chloropyridine
(33 mL) and John-Phos ligand (10.4 mg), compound 5e was obtained as a
white solid (30 mg, 39%). M.p. 76–778C; 1H NMR (CDCl3, 300 MHz):
d=1.40 (t, J=7.2 Hz, 3H), 4.42 (q, J=7.2 Hz, 2H), 7.36 (ddd, J=7.8,
4.8, 1.3 Hz, 1H), 7.83 (td, J=7.8, 1.3 Hz, 1H), 8.00 (s, 1H), 8.43 (d, J=
7.8 Hz, 1H), 8.75 ppm (d, J=4.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz):
d=14.3, 61.8, 124.7, 125.3, 128.8, 136.8, 145.8, 149.9, 150.2, 153.7,
161.8 ppm; IR: n˜ =3094, 2975, 1713, 1571, 1528 cmÀ1; elemental analysis
calcd (%) for C11H10N2O3 (218.2): C 60.55, H 4.62, N 12.84; found: C
58.46, H 4.91, N 12.38.
1
white solid (40 mg, 53%). M.p. 137–1388C; H NMR (CDCl3, 300 MHz):
d=1.39 (t, J=7.2 Hz, 3H), 4.42 (q, J=7.2 Hz, 2H), 4.26 (q, J=7.2 Hz,
2H), 8.36 (s, 1H), 9.30 (s, 1H), 9.39 ppm (s, 2H); 13C NMR (CDCl3,
75 MHz): d=14.4, 61.8, 121.4, 135.3, 144.8, 157.7, 160.1, 160.8 ppm; IR:
n˜ =3127, 2991, 1723, 1606, 1575 cmÀ1; elemental analysis calcd (%) for
C10H9N3O3 (219.2): C 54.79, H 4.14, N 19.17; found: C 54.77, H 4.13, N
19.18.
General procedure for PivOK-assisted, C2-selective direct arylation of
2a: Compound 2a (50 mg, 0.27 mmol) was placed in
(10 mL) with potassium carbonate (75 mg, 0.54 mmol), PivOH (9 mg,
0.08 mmol), Pd(OAc)2 (3 mg, 0.014 mmol) and PtBu3·HBF4 (7.8 mg,
a sealed tub
Compound 5 f: By following the above procedure with 3-bromoquinoline
(48 mL) and John-Phos ligand (10.4 mg), compound 5 f was obtained as a
yellow solid (35 mg, 37%). M.p. 111–1128C; 1H NMR (CDCl3,
300 MHz): d=1.43 (t, J=7.2 Hz, 3H), 4.46 (q, J=7.2 Hz, 2H), 7.61 (td,
J=7.2, 0.7 Hz, 1H), 7.79 (td, J=7.2, 0.7 Hz, 1H), 7.94 (d, J=8.2 Hz,
1H), 8.03 (s, 1H), 8.14 (d, J=8.2 Hz, 1H), 9.08 (d, J=1.9 Hz, 1H),
9.42 ppm (d, J=1.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=14.6, 62.1,
120.5, 127.3, 127.8, 128.5, 129.1, 129.7, 131.5, 136.9, 148.6, 149.1, 150.0,
153.5 162.1 ppm; IR: n˜ =3430, 3327, 2975, 1704, 1569 cmÀ1; elemental
analysis calcd (%) for C15H12N2O3 (268.3): C 67.16, H 4.51, N 10.44;
found: C 66.87, H 4.77, N 10.15.
ACHTUNGTRENNUNG
0.027 mmol). A solution of aryl halide (0.27 mmol) in dry dioxane (1 mL)
was added and the resulting mixture was purged with nitrogen. The mix-
ture was stirred at 1108C for 18 h. After filtration through Celite and
concentration in vacuo, the crude product was purified by flash column
chromatography on silica gel using a mixture of petroleum ether/ethyl
acetate as the eluent.
Compound 4b: By following the above procedure with 4-chlorobenzoni-
trile (37 mg), compound 4b was obtained as a white solid (27 mg, 52%).
M.p. 192–1938C; 1H NMR (CDCl3, 300 MHz): d=1.62 (s, 9H), 7.74 (dd,
J=8.4, 1.2 Hz, 2H), 8.11 (s, 1H), 8.13 ppm (dd, J=8.4, 1.2 Hz, 2H);
13C NMR (CDCl3, 75 MHz): d=28.3, 82.6, 114.0, 118.4, 127.4, 132.9,
Compound 5g: By following the above procedure with 5-bromopyrimi-
dine (56 mg) and John-Phos ligand (10.4 mg), compound 5g was obtained
as
a
white solid (39 mg, 51%). M.p. 89–908C; 1H NMR (CDCl3,
136.7, 150.2, 160.2, 166.0 ppm; IR (KBr): n˜ =3133, 2976, 2230, 1712 cmÀ1
;
300 MHz): d=1.42 (t, J=6.9 Hz, 3H), 4.45 (q, J=6.9 Hz, 2H), 8.04
(s,1H), 9.28 (s, 1H), 9.42 ppm (s, 2H); 13C NMR (CDCl3, 75 MHz): d=
14.5, 62.4, 122.3, 125.6, 129.7, 150.2, 150.8, 156.3, 159.6, 161.6 ppm; IR:
n˜ =3110, 2986, 1713, 1572, 1313, 1078 cmÀ1; elemental analysis calcd (%)
for C10H9N3O3 (219.2): C 54.79, H 4.14, N 19.17; found: C 54.73, H 4.21,
N 18.60.
elemental analysis calcd (%) for C15H14N2O2S (286.3): C 62.92, H 4.93, N
9.78, S 11.20; found: C 62.85, H 4.98, N 9.72, S 11.25. Analytical data are
consistent with those reported in the literature.[9b]
Compound 4e: By following the above procedure using 2-chloroquino-
line (44 mg), compound 4e was obtained as a white solid (21 mg, 38%).
M.p. 160–1618C; 1H NMR (CDCl3, 300 MHz): d=1.64 (s, 9H), 7.55 (td,
J=8.0, 1.3 Hz, 1H), 7.73 (td, J=8.0, 1.3 Hz, 1H) 7.83 (d, J=8.0 Hz, 1H),
8.11 (d, J=8.6 Hz, 1H), 8.18 (s, 1H), 8.25 (d, J=8.6 Hz, 1H), 8.45 ppm
(d, J=8.6 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=28.3, 82.2, 118.2,
127.5, 127.9, 129.0, 129.4, 129.5, 130.2, 137.2, 147.8, 149.7, 150.6, 160.6,
170.1 ppm; IR (KBr): n˜ =1716, 2931, 2980, 3002, 3061, 3133 cmÀ1; ele-
mental analysis calcd (%) for C17H16N2O2S (312.4): C 65.36, H 5.16, N
8.97, S 10.26; found: C 65.23, H 5.18, N 8.93, S 10.31. Analytical data are
consistent with those reported in the literature.[9b]
General procedure for K2CO3-assisted, C5-selective direct arylation of
15: Compound 15 (38 mg, 0.27 mmol) was placed in a sealed tube
(10 mL) with potassium carbonate (75 mg, 0.54 mmol), PdACHTNUTRGNEUNG(OAc)2 (3 mg,
0.014 mmol) and dppe ligand (11 mg, 0.027 mmol). A solution of aryl
halide (0.27 mmol) in dry dioxane (1 mL) was added and the resulting
mixture was purged with nitrogen. The mixture was stirred at 1108C for
18 h. After filtration through Celite and concentration in vacuo, the
crude product was purified by flash column chromatography on silica gel
using a mixture of petroleum ether/ethyl acetate as the eluent.
General procedure for K2CO3-assisted, C5-selective direct arylation of
1a: Compound 1a (50 mg, 0.35 mmol) was placed in a sealed tube
(10 mL) with potassium carbonate (96 mg, 0.70 mmol), PdACTHNUTRGNEUNG(OAc)2
(4.5 mg, 0.018 mmol) and ligand (0.035 mmol). A solution of aryl halide
(0.35 mmol) in dry dioxane (1 mL) was added and the resulting mixture
was purged with nitrogen. The mixture was stirred at 1108C for 18 h.
After filtration through Celite and concentration in vacuo, the crude
product was purified by flash column chromatography on silica gel using
a mixture of petroleum ether/ethyl acetate as the eluent.
Compound 17d: By following the above procedure with 2-bromobenzo-
nitrile (49 mg), compound 17d was obtained as a white solid (24 mg,
37%). M.p. 98–998C; 1H NMR (CDCl3, 300 MHz): d=3.86 (s, 3H), 7.51
(dd, J=0.6, 7.5 Hz, 1H), 7.56 (td, J=1.2, 7.8 Hz, 1H), 7.66 (td, J=1.2,
7.8 Hz, 1H), 7.79 (dd, J=0.9, 7.8 Hz, 1H), 8.91 ppm (s, 1H); 13C NMR
(CDCl3, 75 MHz): d=52.7, 113.9, 117.3, 129.8, 131.3, 132.5, 133.2, 134.0,
141.6, 143.3, 153.1, 161.8 ppm; IR: n˜ =3074, 2232, 1710 cmÀ1; elemental
analysis calcd (%) for C12H8N2O2S (244.3): C 59.00; H 3.30, N 11.47, S
13.13; found: C 59.00, H 3.37, N 11.22, S 13.33.
Compound 5c: By following the above procedure with 4-bromoanisole
(44 mL) and John-Phos ligand (10.4 mg), compound 5c was obtained as a
white solid (47 mg, 54%). M.p. 70–718C; 1H NMR (CDCl3, 300 MHz):
d=1.41 (t, J=7.2 Hz, 3H), 3.86 (s, 3H), 4.41 (q, J=7.2 Hz, 2H), 7.00 (d,
J=9.0 Hz, 2H), 7.85 (s, 1H), 8.07 ppm (d, J=9.0 Hz, 2H); 13C NMR
(CDCl3, 75 MHz): d=14.4, 55.5, 61.4, 113.9, 119.3, 125.4, 130.3, 148.5,
155.9, 161.3, 162.3 ppm; IR (KBr): n˜ =3139, 2975, 1694, 1608, 1504, 1182,
1077, 847, 790, 643, 617, 547 cmÀ1; elemental analysis calcd (%) for
C13H13NO4 (247.2): C 63.15, H 5.30, N 5.67; found: C 62.84, H 5.61, N
6.02.
General procedure for PivOK-assisted, C5-selective direct arylation of
15: Compound 15 (38 mg, 0.27 mmol) was placed in a sealed tube
(10 mL) with potassium carbonate (75 mg, 0.54 mmol), PivOH (9 mg,
0.08 mmol), PdACTHUNRGTNEUNG(OAc)2 (3 mg, 0.014 mmol) and ligand (0.027 mmol). A
solution of aryl halide (0.27 mmol) in dry dioxane (1 mL) was added and
the resulting mixture was purged with nitrogen. The mixture was stirred
at 1108C for 18 h. After filtration through Celite and concentration in
vacuo, the crude product was purified by flash column chromatography
on silica gel using a mixture of petroleum ether/ethyl acetate as the
eluent.
Compound 5d: By following the above procedure with 4-bromo-N,N-di-
methylaniline (70 mg) and dppf ligand (19.4 mg), compound 5d was ob-
tained as a pale brown solid (30 mg, 33%). M.p. 83–848C; 1H NMR
Compound 17b: By following the above procedure with 4-chlorobenzoni-
trile (37 mg) and PCy3·HBF4 (9.9 mg), compound 17b was obtained as a
yellow solid (43 mg, 61%). M.p. 139–1408C; 1H NMR (CDCl3,
Chem. Eur. J. 2011, 17, 14450 – 14463
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
14461