ORGANIC
LETTERS
2003
Vol. 5, No. 17
3037-3039
Palladium-Catalyzed Intermolecular
r-Arylation of N-Protected
2-Piperidinones
Janine Cossy,* Arnault de Filippis, and Domingo Gomez Pardo
Laboratoire de Chimie Organique associe´ au CNRS, ESPCI, 10 rue Vauquelin,
75231 Paris Cedex 05, France
Received June 5, 2003
ABSTRACT
The r-arylation of the zinc enolate of N-protected 2-piperidinones with aryl bromides in the presence of a palladium catalyst is described as
a general method.
The addition of nucleophiles to aryl halides can occur by
three pathways: addition-elimination (via a Meisenheimer
complex), elimination-addition (benzyne), or electron trans-
fer (radical, anion-radical).1 More recently, palladium-
catalyzed coupling reactions of aryl halides or pseudohalides
with nucleophiles have been developed.2 It has been shown
that the palladium-catalyzed intermolecular coupling of
halides and keto enolates or ester enolates is a useful method
for synthesizing R-aryl ketones3 and R-aryl esters.4 Arylation
of other carboxylic acid derivatives such as amides are less
common.5 Intermolecular arylation of the lithium enolate of
N,N-dimethylamides with aryl halides in the presence of a
palladium catalyst occurs in moderate yields and is not
general.5a Intramolecular arylation of N-(2-halophenyl)amides
was also reported and led to R-phenylpyrrolidinones.5
To our knowledge, only one example of palladium-
catalyzed intermolecular coupling of aryl halides with a
cyclic amide, the N-methylpyrrolidinone, has been reported.5a
Here, we would like to report a general method for the
R-arylation of piperidinone enolates (Scheme 1).
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10.1021/ol0350036 CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/24/2003