Palladium-Catalyzed Amide-Directed Hydrocarbofunctionalization of 3‑Alkenamides with Alkynes

A Pd-catalyzed carboxamide-directed hydrocarbofunctionalization reaction of unactivated alkenes with different alkynes has been developed. An 8-aminoquinoline auxiliary was utilized to increase the reactivity of the alkene and control the regioselectivity via the formation of thermodynamically favored five-membered palladacycle intermediate. 3-Alkene carboxamides bearing a C4-substituted alkene group reacted with a variety of terminal alkynes in the presence of an ortho-phenyl benzoic acid promoter, yielding γ-alkynylated products with high yields and regioselectivity. 3-Butenamide underwent a three-component coupling reaction with internal alkynes and carboxylic acids to give vinyl ester products. Preliminary mechanistic studies indicate that the intramolecular migratory insertion of alkynyl or vinyl palladium species into the CC bond is responsible for the γ-selective alkynylation or alkenylation of the alkene group.

本研究开发了一种以酰胺为导向基团的钯催化氢碳官能化反应，可实现未活化烯烃与多种炔烃的偶联。研究中采用8-氨基喹啉助剂，通过生成热力学有利的五元钯环中间体，提升烯烃的反应活性并精准控制区域选择性。带有C4位取代烯烃基团的3-烯基酰胺，可在邻苯基苯甲酸促进剂作用下与多种端炔发生反应，以高收率和优异区域选择性得到γ-炔基化产物。3-丁烯酰胺可与内炔及羧酸发生三组分偶联反应，生成乙烯基酯类产物。初步机理研究表明，炔基或乙烯基钯物种向烯烃碳碳双键的分子内迁移插入，是实现烯烃γ-位选择性炔基化或烯基化的关键步骤。