ORGANIC LETTERS
Unexpected Formation of Aryl Ketones by Palladium-Catalyzed Coupling of Aryl Bromides with Vinylic Acetates
2007 Vol. 9, No. 18 3623-3625
Mickae1 l Jean,§ Jacques Renault,§ Philippe Uriac,*,§ Marc Capet,† and Pierre van de Weghe*,§,‡ EA Substances Liche´ niques et Photoprotection, Faculte´ de Pharmacie, UniVersite´ de Rennes 1, 2 aVenue du Professeur Le´ on Bernard, F-35043 Rennes Cedex, France, Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP96205, F-35762 Saint-Gre´ goire, France and Laboratoire de Chimie Organique et Bioorganique associe´ au CNRS, ENSC-Mu, UniVersite´ de Haute Alsace, 3 rue A. Werner, F-68093 Mulhouse Cedex, France
[email protected];
[email protected] Received June 25, 2007
ABSTRACT
A palladium-catalyzed coupling reaction of aryl bromides with vinylic acetates in the presence of tributyltin methoxide has been described. Unexpected formation of aryl ketones was obtained. Preliminary mechanistic studies indicated that the reaction proceeded by the addition of the aryl moiety in the coordination sphere of palladium to a ketene.
In 1983 Migita disclosed R-phenylation of ketones via tin enolates catalyzed by a palladium complex. The reaction of tributyltin enolates, prepared in situ from tributyltin methoxide and enol acetates, with aryl bromides in the presence of dichlorobis(tri-o-tolylphosphine)palladium was found to give R-aryl ketones in good yields.1 In spite of its synthetic interest, few developments and applications of this reaction were reported.2 Recently Buchwald and Hartwig described independently another Pd-catalyzed R-arylation of ketones, the enolates being generated in situ from ketones and bases like NaO-t-Bu.3 To our knowledge, there has been no report §
Faculte´ de Pharmacie, Universite´ de Rennes 1. Bioprojet-Biotech. ‡ COB, Universite ´ de Haute Alsace. (1) (a) Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita, T. J. Chem. Soc., Chem. Commun. 1983, 344-345. (b) Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita, T. Bull. Chem. Soc. Jpn. 1984, 57, 242-246. (2) Selected examples: (a) Gupta, M.; Nair, V. Tetrahedron Lett. 2005, 46, 1165-1167. (b) Nicolaou, K. C.; Xu, H. Chem. Commun. 2006, 600602. (3) (a) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108-11109. (b) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 12382-12383. (c) Culkin, D. C.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234-245. (d) Hartwig, J. F. Synlett 2006, 1283-1294. †
10.1021/ol7015065 CCC: $37.00 Published on Web 08/01/2007
© 2007 American Chemical Society
concerning R-arylation of aldehydes. Here, we first describe that palladium complexes efficiently catalyze intermolecular addition of aryl bromides to various vinylic acetates in the presence of tributyltin methoxide leading to aryl ketones. In a preliminary experiment, we treated 1a with vinyl acetate 2a and Bu3SnOMe in the presence of dichlorobis(tri-o-tolylphosphine)palladium in toluene at 100 °C. No R-arylation of the aldehyde was observed, but acylation of the benzothiazole was achieved affording 3a in a moderate yield (Scheme 1). Because of this surprising inversion of selectivity we decided to study this reaction. We began to focus on optimizing the reaction conditions using the 2-bromonaphthalene 1b as starting material (Table
Scheme 1.
Preliminary Experiment
Table 1. Palladium-Catalyzed Coupling of Aryl Bromides with Vinylic Acetates
As shown in Table 1, the Pd-catalyzed coupling of aryl bromides with vinylic acetates provided a general method for the preparation of various aryl ketones. When the reaction was carried out with vinylic acetates 2a and 2b, we obtained lower yields than with 2c and 2d. The yield was improved by using 5-10 equiv of these volatile enolates (bp
