Efficient synthesis of alpha-aryl esters by room-temperature palladium-catalyzed coupling of aryl halides with ester enolates.
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.
Jørgensen
Morten
M
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, USA.
Lee
Sunwoo
S
Liu
Xiaoxiang
X
Wolkowski
Joanna P
JP
Hartwig
John F
JF
D000085:Acetates / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D004952:Esters / Q000138:chemical synthesis*; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D013696:Temperature
D000085:Acetates; D000588:Amines; D004952:Esters; D006841:Hydrocarbons, Aromatic; D006846:Hydrocarbons, Halogenated; D008024:Ligands; D009942:Organometallic Compounds; D010165:Palladium; C089834:tert-butyl acetate