Efficient Synthesis of α-Aryl Esters by Room-Temperature Palladium-Catalyzed Coupling of Aryl Halides with Ester Enolates

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 α-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 α,α-disubstituted esters were developed with LiNCy₂ 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.