ORGANIC
LETTERS
2004
Vol. 6, No. 24
4395-4398
Unexpected Cross-Coupling Reaction
between o-Chloroaryl Ketones and
Organomanganese Reagents
Ge´rard Cahiez,* Denis Luart, and Fabien Lecomte
Laboratoire de Chimie Organique Se´lectiVe et de Chimie Organome´tallique (SOSCO),
UMR 8123 CNRS-UCP-ESCOM, 13, BouleVard de l’Hautil,
F-95092 Cergy-Pontoise, France
Received June 18, 2004 (Revised Manuscript Received September 7, 2004)
ABSTRACT
Alkyl- and arylmanganese reagents react with o-chloro or o-bromoaryl ketones to give the substituted ketones in high yields. The cross-
coupling reaction is performed under mild conditions (
−60 to
+
40
°
C, 30 min to 4 h) and takes place with excellent chemoselectivity.
The discovery of new economically and environmentally
friendly alternatives to palladium and nickel catalyzed-cross-
coupling reactions between an organic halide and an organo-
metallic compound is of current interest, especially for large-
scale application. In this field, we have recently reported the
first manganese-catalyzed cross-coupling reaction between
activated aryl halides (X ) Cl, Br, F) or activated aryl methyl
ethers and organomagnesium reagents.1
reacts with o-chlorovalerophenone or o-chlorobenzophenone
to lead to the corresponding coupling products in good yields
(88-89%, Scheme 1).
Scheme 1. Mn-Catalyzed Cross-Coupling Reaction between
PhMgCl and o-Chloroaryl Ketones
Recently, we have tried to extend this reaction to a new
family of activated aryl halides: the o-chloro or o-bromoaryl
ketones.2
The first preliminary experiments were quite encouraging
since in THF at 0 °C, phenylmagnesium chloride quickly
* Corresponding author: Fax: +33(01)30756201.
(1) (a) Cahiez, G.; Lepifre, F.; Ramiandrasoa, P. Synthesis 1999, 12,
2138. It should be noted that organomanganese reagents have been used to
perform various coupling reactions. For some leading references see the
following. Acylation: (b) Cahiez, G.; Laboue, B. Tetrahedron Lett. 1989,
30, 7369; 1992, 33, 4439. (c) Cahiez, G.; Razafintsalama, L.; Laboue, B.;
Chau, F. Tetrahedron Lett. 1998, 39, 849. (d) Cahiez, G.; Me´tais, E.
Tetrahedron: Asymmetry 1996, 8, 1373. Cu-catalyzed alkylation and Fe-
catalyzed alkylation: (e) Cahiez, G.; Marquais, S. Pure and Appl. Chem.
1996, 68, 53. Pd-catalyzed arylation: (f) Riguet, E.; Alami, M.; Cahiez, G.
J. Organomet. Chem. 2001, 624, 376. For reviews, see: (g) Cahiez, G.
Butyl Manganese Chloride in Encyclopedia of Reagents for Organic
Synthesis; Paquette, L., Ed.; Wiley: Chichester, 1995; Vol. 2, p 925. (h)
Cahiez, G. Manganese (II) Chloride. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L., Ed.; Wiley: Chichester, 1995; Vol. 5, p
3227. (i) Cahiez, G. An. Quim. 1995, 91, 561.
Unfortunately, all of our attempts to perform the reaction
with a more reactive organomagnesium compound such as
(2) Until now, only very few examples of coupling reactions were
described with o-halogenoaryl ketones. Boronic acids/Pd catalyses: (a) Shen,
W. Tetrahedron Lett. 1997, 32, 5575. (b) Bei, X.; Crevier, T.; Guram, A.
S.; Jandeleit, B.; Powers, T. S.; Turner, H. W.; Uno, T.; Weinberg, W. H.
Tetrahedron Lett. 1997, 20, 3855. (c) Wolfe, J. P.; Singer, R. A.; Yang, B.
H.; Buchwald, S. L. J. Am. Chem. Soc. 1943, 65, 504. (d) Bei, X.; Turner,
H. W.; Weinberg, W. H.; Guram, A. S. J. Org. Chem. 1953, 18, 6797. (e)
Feuerstein, M.; Doucet, H.; Santelli, M. Synlett 2001, 9, 1458. (f) Jensen,
J. F.; Johannsen, M. Org Lett. 2003, 5, 3025. Vinylstannanes/Ni catalyses:
(g) Shirakawa, E.; Yamasaki, K.; Hiyama, T. J. Chem. Soc., Perkin Trans.
1 1997, 2449; Synthesis 1998, 1544.
10.1021/ol048842g CCC: $27.50
© 2004 American Chemical Society
Published on Web 11/05/2004