1876
E. Maerten et al.
LETTER
reasonable times (TOF = 20 h–1 with 2,3-dichloropyri-
dine).10 Small amounts of the diketone product were also
formed from 2,6-dichloropyridine (two activated posi-
tions). Only the activated 4-position of 4,7-dichloroquin-
oline reacted to form ketone adduct (TOF = 7 h–1).10 As
usually observed with chloride substrates and Pd cata-
lysts, some reduction compounds were also obtained.
with N2, the autoclave was heated to 80 °C under stirring for 40 min.
Then, the autoclave was cooled to 20 °C and a solution of phenyl-
boronic acid (268 mg, 2.2 mmol) in dioxane (5 mL) was added un-
der N2. The autoclave was flushed with CO, pressurized to 50 bar
and heated to 140 °C for 22 h. After cooling to 20 °C, the solution
was analyzed by quantitative GLC. For isolating the products,
CH2Cl2 (15 mL) was added to the reaction mixture, the solution was
washed with aq brine and dried over MgSO4. The solvent was re-
moved in vacuo and the residue was purified by silica gel chroma-
tography to give analytically pure (1H and 13C NMR, MS) ketone
products.
In summary, we have extended the scope of the carbony-
lative coupling reaction to the attractive heteroaryl chlo-
rides. The use of N-heterocyclic carbene ligand enables to
overcome the poor reactivity of this class of substrates and
leads to good selectivities towards ketones. Other sub-
strates are currently being tested to generalize this method
and reaction conditions are still under investigation to op-
timize the process.
References
(1) For reviews, see: (a) Miyaura, N.; Suzuki, A. Chem. Rev.
1995, 95, 2457. (b) Suzuki, A. In Handbook of
Organopalladium Chemistry for Organic Synthesis, Vol 1;
Negishi, E. I., Ed.; John Wiley and Sons, Inc.: Hoboken,
2002, 249–262.
(2) For a recent review, see: Littke, A. F.; Fu, G. C. Angew.
Chem. Int. Ed. 2002, 41, 4176.
(3) (a) Ishiyama, T.; Kizaki, H.; Miyaura, N.; Suzuki, A.
Tetrahedron Lett. 1993, 34, 7595. (b) Ishiyama, T.; Kizaki,
H.; Hayashi, T.; Suzuki, A.; Miyaura, N. J. Org. Chem.
1998, 63, 4726.
(4) (a) Couve-Bonnaire, S.; Carpentier, J.-F.; Mortreux, A.;
Castanet, Y. Tetrahedron Lett. 2001, 42, 3689. (b) Couve-
Bonnaire, S.; Carpentier, J.-F.; Mortreux, A.; Castanet, Y.
Tetrahedron 2003, 59, 2793.
(5) (a) Zhang, C.; Huang, J.; Trudell, M. T.; Nolan, S. P. J. Org.
Chem. 1999, 64, 3804. (b) Grasa, G. A.; Viciu, M. S.;
Huang, J.; Zhang, C.; Trudell, M. L.; Nolan, S. P.
Organometallics 2002, 21, 2866. (c) McGuiness, D.;
Cavell, K. J. Organometallics 2000, 19, 741.
Y
Cl
Pd(OAc)2 - A
CO, PhB(OH)2
Cs2CO3
X
N
Cl
N
X = COPh, Y = ClH : 86%
X = Ph,CO Y = ClH : 10%
X = COPh, Y = HCl : 4%
23 h, 83% conv.
Y
Cl
Cl
Pd(OAc)2 - A
CO, PhB(OH)2
Cs2CO3
X
N
N
X = COPh, Y = ClH : 72%
X = Ph,CO Y = ClH : 13%
X = COPh, Y = HCl : 15%
4 h, 90% conv.
Pd(OAc)2 - A
CO, PhB(OH)2
Cs2CO3
X
Y
N
Cl
Cl
N
(d) Gstöttmayr, C. W. K.; Böhn, V. P. M.; Herdtweck, E.;
Grosche, M.; Herrmann, W. A. Angew. Chem. Int. Ed. 2002,
41, 1363.
X = COPh, Y = ClH : 51%
X = Ph,CO Y = ClH : 33%
X = COPh, Y = PhCl : 8%
X = COPh, Y = COPh : 8%
90 h, 71% conv.
(6) As our investigations neared completion, palladium-
imidazolium carbonylative coupling of more actived aryl
diazonium ions with aryl boronic acids was
Cl
N
X
Pd(OAc)2 - A
CO, PhB(OH)2
Cs2CO3
reported:Andrus, M. B.; Ma, Y.; Zang, Y.; Song, C.
Tetrahedron Lett. 2002, 43, 9137.
Cl
N
Y
(7) (a) Littke, A. D.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000,
122, 4020. (b) Yin, J.; Rainka, M. P.; Zhang, X.-X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1162.
(8) Arduengo, A. J. III; Krafczyk, R.; Schmutzler, R.; Craig, H.
A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M.
Tetrahedron 1999, 55, 14523.
X = COPh, Y = ClH : 66%
X = Ph,CO Y = ClH : 22%
22 h, 83% conv.
X = H,
unknown
Y = Cl : 8%
: 4%
Scheme 3 Carbonylative Suzuki cross-coupling of dichloroazines
(9) In a number of coupling reactions of aryl chlorides, it was
found that a 1:1 Pd-ligand ratio (ligand = N-heterocyclic
carbene, phosphine, …) led to optimum reaction rates (see
ref. 2 and ref. 5b for N-heterocyclic carbene ligands).
(10) TOF: turnover frequencies defined as the number of moles
of substrate transformed per mole of catalyst and per hour
calculated after one hour of reaction.
Typical Procedure
In a typical experiment, a 50 mL stainless steel autoclave equipped
with a magnetic stirring bar was charged with Pd(OAc)2 (13.5 mg,
0.06 mmol), the imidazolium salt (0.12 mmol) (A and B from Strem
Chemical, C from Acros), 1b (200 mL, 2.1 mmol), Cs2CO3 (1.3 g,
4.0 mmol) and 1,4-dioxane (10 mL). After flushing the atmosphere
Synlett 2003, No. 12, 1874–1876 © Thieme Stuttgart · New York