Palladium-Catalyzed Intermolecular α-Arylation of Zinc Amide Enolates under Mild Conditions

• Published in: Journal of the American Chemical Society 2006-04, Vol.128 (15), p.4976-4985
• Main Authors: Hama, Takuo, Culkin, Darcy A, Hartwig, John F
• Format: Article
• Language: English
• Subjects: Amides - chemistry; Benzene Derivatives - chemical synthesis; Benzene Derivatives - chemistry; Catalysis; Hydrocarbons, Brominated - chemistry; Ketones - chemical synthesis; Ketones - chemistry; Lithium Compounds - chemistry; Morpholines - chemistry; Organometallic Compounds - chemistry; Palladium - chemistry; Vinyl Compounds - chemistry; Zinc - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja056076i

The intermolecular α-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 α-bromo amides, with Reformatsky reagents generated in situ from α-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 °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.