title: Pd-catalyzed monoselective ortho-C-H alkylation of N-quinolyl benzamides: evidence for stereoretentive coupling of secondary alkyl iodides.
abstract: We report a method for the monoselective alkylation of ortho-C-H bonds of N-quinolyl benzamides with both primary and secondary alkyl halides under palladium catalysis. With promotion by NaHCO3 and (BnO)2PO2H or (PhO)2PO2H, symmetric benzamide substrates can be selectively ortho-alkylated to give either mono- or dialkylated products by simply adjusting the amount of NaHCO3 applied. The use of phosphate notably improves the alkylation yield, although it may not be directly involved in C-H palladation or the subsequent functionalization step. Kinetic isotope effect studies indicate that C-H palladation is not the rate-limiting step. Examination of the reactions of an isolated palladacycle intermediate with both cis- and trans-4-methylcyclohexyl iodides revealed surprising stereoretentive couplings of these alkyl iodides. This evidence strongly suggests that the functionalization of the palladacycle with secondary alkyl iodides proceeds via a rarely precedented concerted oxidative addition pathway.
authors.affiliation: Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: He
authors.forename: William A
authors.initials: WA
authors.lastname: Nack
authors.forename: Gong
authors.initials: G
authors.lastname: Chen