Synfacts 2007(2): 0193-0193  
DOI: 10.1055/s-2006-955803
Metal-Mediated Synthesis
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Aryl Ketones by Coupling of Aryl Bromides with an Acyl Equivalent

Contributor(s):Paul Knochel, Andrei Gavryushin
A. Takemiya, J. F. Hartwig*
Yale University, New Haven, USA
Palladium-Catalyzed Synthesis of Aryl Ketones by Coupling of Aryl Bromides with an Acyl Anion Equivalent
J. Am. Chem. Soc.  2006,  128:  14800-14801  
Further Information

Publication History

Publication Date:
23 January 2007 (online)


Significance

The Pd-catalyzed cross-coupling reaction of aryl halides with C-H acidic compounds has recently been widely used for the preparation of aryl ketones, esters and amides. Herein, a new elegant method of the synthesis of aryl ketones is reported. It utilizes acyl anion equivalents, readily available from the corresponding aldehydes. This approach avoids the use of strongly nucleophilic organometallic reagents, often incompatible with functional groups in the molecule. The preparation of tert-butylhydrazones from aldehydes is quite simple, and the coupling reaction is highly versatile and easy to perform.

Comment

Hydrazones of aldehydes as acyl anion equivalents were first introduced by J. E. Baldwin (J. E. Baldwin, R. M. Adlington, I. M. Newington J. Chem. Soc., Chem. Comm. 1986, 176-178). They were shown to react directly with organic electrophiles (C. W. Alexander, S. Y. Lin, R. K. Dieter J. Organomet. Chem. 1995, 503, 213-220). Their acidity is close to the acidity of an α-proton of carbonyl compounds. The addition of an electrophile to those hydrazones gives diaza­allyl intermediates. The chemistry of these reagents remains mostly unexplored. On changing the tert-butyl residue of the hydrazone to a phenyl group, its N-arylation proceeds under the same conditions.