9714
K. Arentsen et al. / Tetrahedron 61 (2005) 9710–9715
This suspension was sonicated (3!15 min) and the super-
natant was then removed by filter cannula. After concen-
trating the filtrate in vacuo, the title compound was
4-chlorotoluene and phenylboronic acid was complete
after 48 h. The crude residue was purified by column
chromatography (petroleum ether) to furnish an off-white
1
24 1
precipitated from THF at K45 8C (143 mg, 60%).
NMR (C D , 300 MHz): d 2.95 (s, 8H), 1.97 (s, 36H).
NMR (C D , 75 MHz): d 219.7 (Pd–C), 55.4 (NCH CH N),
H
C
solid. Mp: 42 8C (lit. mp 49 8C).
H NMR (CDCl3,
1
3
300 MHz): d 7.50 (d, JZ7.5 Hz, 2H), 7.41 (d, JZ8.1 Hz,
2H), 7.34 (t, JZ7.5 Hz, 2H), 7.24 (t, JZ7.2 Hz, 1H), 7.16
6
6
6
6
2
2
C
13
4
5.6 (C(CH ) ), 31.2 (CH ). LRMS m/z (EI) 470 [M ], 183
3
(d, JZ7.7 Hz, 2H), 2.31 (s, 3H). C NMR (CDCl3,
3
3
C
M KPd{cyclo-C[N(t-Bu)CH ] }]. Anal. Calcd for
[
C H N Pd: C, 56.10; H, 9.42; N, 11.89. Found: C, 55.
75 MHz): d 140.1 (C ), 137.3 (C ), 136.0 (C ), 128.4
(CH ), 127.7 (CH ), 125.9 (CH ), 28.7 (CH ). Spectro-
ar ar ar 3
2
2
ar
ar
ar
2
2
44
4
2
4
9
4; H, 9.60; N, 11.72.
scopic data corresponds to that reported in the literature.
4
.1.5. General procedure for amination of 4-chlorotoluene
with aniline. An ampoule was charged with catalyst
4.2.3. Methyl-(4-phenyl)-benzoate (entries 11–15). The
coupling of methyl-4-chlorobenzoate and phenylboronic
acid was complete after 16 h. After cooling the reaction
mixture to ambient temperature, it was diluted with diethyl
ether and filtered through a small amount of silica gel. The
insoluble residues were washed with diethyl ether. The
solvent was removed in vacuo and the crude product was
purified by column chromatography (petroleum ether/ethyl
acetate 90:10). This afforded the title compound as a white
(
(
0.016 mmol) and KOt-Bu (133 mg, 1.19 mmol). Dioxane
4 mL) was added, followed by aniline (87 mL, 0.95 mmol)
and 4-chlorotoluene (93 mL, 0.79 mmol). The reaction
mixture was stirred at 100 8C for 5 h. After this time, the
mixture was cooled to room temperature, diluted with
diethyl ether and filtered through a small amount of silica
gel. The insoluble residues were washed with diethyl ether.
The solvent was removed in vacuo and the crude product
was purified by column chromatography (petroleum ether/
ethyl acetate 95:5). This yielded the product, phenyl-p-
tolylamine, as an off-white solid. Mp: 82–84 8C (lit. mp 88–
2
5 1
solid. Mp: 109 8C (lit. mp 117–118 8C). H NMR (CDCl3,
300 MHz): d 8.04 (d, JZ8.6 Hz, 2H), 7.61–7.52 (m, 4H),
7.43–7.29 (m, 3H), 3.87 (s, 3H). C NMR (CDCl3,
1
3
75 MHz): d 167.4 (COOMe), 146.1 (C ), 140.4 (C ),
ar
ar
2
2 1
8
7
1
8.5 8C).
.00 (d, 2H), 6.95–6.85 (m, 5H), 6.75 (t, 1H), 5.50 (br s,
H NMR (CDCl , 300 MHz): d 7.10 (d, 2H),
130.1 (CH ), 129.3 (CH ), 129.3 (C ), 128.5 (CH ), 127.7
ar ar ar ar
3
(CH ), 127.6 (CH ), 52.6 (OCH ). LRMS m/z (EI) 212
ar
ar
3
1
H), 2.20 (s, 3H). C NMR (CDCl , 75 MHz): d 144.3
3
C
C
3
[M ], 181 [M KOCH ]. Spectroscopic data corresponds
3
25
to that reported in the literature.
(
C ), 140.7 (C ), 131.3 (C ), 130.3 (CH ), 129.7 (CH ),
ar
ar
ar
ar
ar
1
LRMS m/z (EI) 183 [M ], 167 [M KCH ]. Spectroscopic
20.7 (CH ), 119.3 (CH ), 117. 3 (CH ), 21.1 (CH ).
ar ar ar 3
C
C
3
2
3
data corresponds to that reported in the literature.
Acknowledgements
4.2. Suzuki–Miyaura reactions of aryl chlorides using
bis-carbene palladium complex catalysts
We thank the EPSRC for financial support of this work. We
also thank AstraZeneca, CEM, BBSRC, Novartis and GSK
for support of our programme. We also gratefully acknowl-
edge the contributions of Dr. A. G. Avent, Dr. A. Abdul-
Sada and Dr. P. B. Hitchcock.
General procedure. To an ampoule charged with phenyl-
boronic acid (67 mg, 0.550 mmol) and tetra-n-butylammo-
nium bromide (TBAB) (16 mg, 0.050 mmol) was added the
catalyst (0.015 mmol) and KOMe (105 mg, 1.50 mmol).
Toluene (3 mL) was then transferred to the ampoule. After
the addition of the aryl chloride (0.50 mmol), the reaction
mixture was stirred at 40 8C. The reaction was monitored by
TLC to check for the disappearance of the aryl chloride. The
solution was cooled to ambient temperature and ethyl
acetate (10 mL) and sodium hydroxide (1 M, 10 mL) were
added. This mixture was filtered and the aqueous phase was
removed. The organic layer was washed with sodium
chloride (20% w/v, 2!5 mL). The organic layer was then
References and notes
1. (a) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998. (b) Tsuji, J.
Palladium Reagents and Catalysts; Wiley: Chichester, 1995.
2. Stanforth, S. P. Tetrahedron 1998, 54, 263–303.
3. Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G.
Applications of Organotransition Metal Chemistry; University
Science Books: Mill Valley, CA, 1987.
dried over MgSO and concentrated in vacuo. The crude
4
product was purified by column chromatography.
4
. Zapf, A.; Beller, M. Chem. Commun. 2005, 431–440.
4
4
2
.2.1. 4-Methoxybiphenyl (entries 1–5). The coupling of
-chloroanisole and phenylboronic acid was complete after
2–23 h. The crude residue was purified by column
5. For reviews: (a) Regitz, M. Angew. Chem., Int. Ed. 1996, 35,
725–728. (b) Bourissou, D.; Guerret, O.; Gabbai, F. P.;
Bertrand, G. Chem. Rev. 2000, 100, 39–91. (c) Arduengo, A. J.,
III Acc. Chem. Res. 1999, 32, 913–921.
chromatography, eluting with petroleum ether/ethyl acetate
7:3, to furnish the title compound as an off-white powder.
Mp: 86 8C (lit. mp 91 8C). H NMR (CDCl , 300 MHz): d
9
6. For reviews: (a) Herrmann, W. A. Angew. Chem., Int. Ed.
2002, 41, 1291–1309. (b) Jafarpour, L.; Nolan, S. P. Adv.
Organomet. Chem. 2001, 46, 181–222. (c) Weskamp, T.;
B o¨ hm, V. P. W.; Herrmann, W. A. J. Organomet. Chem. 2000,
600, 12–22.
2
4 1
3
7
2
.50–7.45 (m, 2H), 7.37–7.31 (m, 2H), 7.16 (d, JZ9.7 Hz,
H), 6.90 (m, 1H), 6.75 (d, JZ9.0 Hz, 2H), 3.70 (s, 3H).
C
C
LRMS m/z (EI) 184 [M ], 169 [M KCH ]. Spectroscopic
3
2
4
data corresponds to that reported in the literature.
.2.2. 4-Phenyltoluene (entries 6–10). The coupling of
7. Titcomb, L. R.; Caddick, S.; Cloke, F. G. N.; Wilson, D. J.;
McKerrecher, D. Chem. Commun. 2001, 1388–1389.
8. Caddick, S.; Cloke, F. G. N.; Clentsmith, G. K. B.; Hitchcock,
4