Journal of the American Chemical Society 2002-10-23

Efficient synthesis of alpha-aryl esters by room-temperature palladium-catalyzed coupling of aryl halides with ester enolates.

Morten Jørgensen, Sunwoo Lee, Xiaoxiang Liu, Joanna P Wolkowski, John F Hartwig

Index: J. Am. Chem. Soc. 124(42) , 12557-65, (2002)

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Abstract

A catalytic amount of Pd(dba)(2) ligated by either carbene precursor N,N'-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolium (1) or P(t-Bu)(3) mediated the coupling of aryl halides and ester enolates to produce alpha-aryl esters in high yields at room temperature. The reaction was highly tolerant of functionalities and substitution patterns on the aryl halide. Improved protocols for the selective monoarylation of tert-butyl acetate and the efficient arylation of alpha,alpha-disubstituted esters were developed with LiNCy(2) as base and P(t-Bu)(3) as ligand. In addition, tert-butyl esters, such as those of Naproxen and Flurbiprofen, were prepared from tert-butyl propionate and aryl bromides in high yields in the presence of Pd(dba)(2) and the hindered, saturated heterocyclic carbene ligand precursor.