Palladium-catalyzed intermolecular alpha-arylation of zinc amide enolates under mild conditions.
The intermolecular alpha-arylation and vinylation of amides by palladium-catalyzed coupling of aryl bromides and vinyl bromides with zinc enolates of amides is reported. Reactions of three different types of zinc enolates have been developed. The reactions of aryl halides occur in high yields with isolated Reformatsky reagents generated from alpha-bromo amides, with Reformatsky reagents generated in situ from alpha-bromo amides, and with zinc enolates generated by quenching lithium enolates of amides with zinc chloride. This use of zinc enolates, instead of alkali metal enolates, greatly expands the scope of amide arylation. The reactions occur at room temperature or 70 degrees C with bromoarenes containing cyano, nitro, ester, keto, fluoro, hydroxyl, or amino functionality and with bromopyridines. Moreover, the reaction has been developed with morpholine amides, the products of which are precursors to ketones and aldehydes. The arylation of zinc enolates of amides was conducted with catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) or the highly reactive, dimeric, Pd(I) complex [[P(t-Bu)3]PdBr]2.
Hama
Takuo
T
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, USA.
Culkin
Darcy A
DA
Hartwig
John F
JF
D000577:Amides / Q000737:chemistry*; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D006842:Hydrocarbons, Brominated / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D018020:Lithium Compounds / Q000737:chemistry; D009025:Morpholines / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D000577:Amides; D001555:Benzene Derivatives; D006842:Hydrocarbons, Brominated; D007659:Ketones; D018020:Lithium Compounds; D009025:Morpholines; D009942:Organometallic Compounds; D014753:Vinyl Compounds; D010165:Palladium; C037574:morpholine; D015032:Zinc