title: Palladium-catalyzed alpha-arylation of esters and amides under more neutral conditions.
abstract: Two procedures for the alpha-arylation of carbonyl compounds under conditions that are more neutral than those of reactions of aryl halides with alkali metal enolates are reported. The first procedure rests upon the development of catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) and the highly reactive dimeric Pd(I) complex {P(t-Bu)3]PdBr}2. By this procedure, zinc enolates prepared from alpha-bromo esters and amides react with aryl halides to form alpha-aryl esters and amides in high yields under mild conditions with 1-2 mol % catalyst and with remarkable functional group tolerance. By the second procedure, silyl ketene and silyl ketimine acetals react with aryl bromides in the presence of substoichiometric zinc fluoride, 1 mol % Pd(dba)2, and 2 mol % P(t-Bu)3 in DMF solvent at 80 degrees C. Reactions of zinc tert-butyl acetate and propionate enolates and trimethylsilyl ketene acetals of tert-butyl propionate and methyl isobutyrate with aryl bromides bearing electron-donating and potentially reactive, base-sensitive electron-withdrawing groups and with pyridyl bromides are reported. In addition, the diastereoselective coupling of phenyl bromide with an imide enolate bearing the Evans auxiliary is reported, and this study shows that racemization of base-sensitive stereocenters does not occur during the coupling process under these more neutral conditions.
authors.affiliation: Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, USA.
authors.forename: Takuo
authors.initials: T
authors.lastname: Hama
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Liu
authors.forename: Darcy A
authors.initials: DA
authors.lastname: Culkin
authors.forename: John F
authors.initials: JF
authors.lastname: Hartwig
mesh_terms: D000577:Amides / Q000737:chemistry*; D002384:Catalysis / Q000187:drug effects; D003500:Cyclization; D004952:Esters / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000577:Amides; D004952:Esters; D010165:Palladium