title: Palladium-catalyzed arylation of trimethylsilyl enolates of esters and imides. High functional group tolerance and stereoselective synthesis of alpha-aryl carboxylic acid derivatives.
abstract: A general procedure for the palladium-catalyzed arylation of trimethylsilyl enolates of esters and imides is reported. In the presence of ZnF2 or Zn(O-t-Bu)2 as an additive, the trimethylsilyl enolates of esters, including those bearing alpha-alkoxy derivatives, underwent arylation in high yield with high functional group tolerance. This arylation chemistry was extended to ester derivatives bearing chiral auxiliaries to form new tertiary stereocenters. The arylation of imides bearing the Evans auxiliary proceeded with selectivities up to 90% de. Further, the arylation of the ketal developed by Ley provided alpha-aryl glycolates with excellent diastereoselectivities (90 to >98% de). This reaction provides a convenient route to the synthesis of enantiopure alpha-aryl-alpha-hydroxy esters. Reactions conducted with Zn(O-t-Bu)2 as an additive occurred at room temperature to give enhanced diastereoselectivities with both chiral reagents. Mechanistic studies showed that the reaction conditions are neutral enough that the observed diastereomeric ratios reflect kinetic selectivities.
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut 06510 USA.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Liu
authors.forename: John F
authors.initials: JF
authors.lastname: Hartwig
mesh_terms: D000080:Acetals / Q000737:chemistry; D000478:Alkylation; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis; D004952:Esters / Q000737:chemistry*; D005030:Ethylenes / Q000737:chemistry; D006016:Glycolates / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D006846:Hydrocarbons, Halogenated / Q000737:chemistry; D007094:Imides / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism; D014297:Trimethylsilyl Compounds / Q000737:chemistry*; D017967:Zinc Compounds / Q000737:chemistry; D020002:tert-Butyl Alcohol / Q000031:analogs & derivatives
chemical_list: D000080:Acetals; D002264:Carboxylic Acids; D004952:Esters; D005030:Ethylenes; D006016:Glycolates; D006841:Hydrocarbons, Aromatic; D006846:Hydrocarbons, Halogenated; D007094:Imides; D007659:Ketones; D009942:Organometallic Compounds; D014297:Trimethylsilyl Compounds; D017967:Zinc Compounds; D010165:Palladium; C008223:ketene; D020002:tert-Butyl Alcohol