| A highly regio- and chemoselective methodology for the ligand-directed palladium-catalyzed C-H activation/acetoxylation of sp3 C-H bonds was developed. The reaction was found to be general with a variety of directing groups such as oxime ethers, isoxazolines and pyridines. In addition, the reaction exhibited high selectivity for the acetoxylation of 1° sp 3 C-H bonds.;The ligand directed palladium-catalyzed C-H activation/acetoxylation of sp2 and sp3 C-H bonds was shown to be effective with alternative oxidants such as Oxone and K2S2O 8 in place of PhI(OAc)2. The use of these peroxide based oxidants over PhI(OAc)2 is advantageous because they are cheaper and do not release toxic byproducts such as iodobenzene.;A comprehensive investigation to elucidate the factors affecting the C-H activation/acetoxylation by one ligand over another was conducted. It was determined that in the presence of multiple chelating functionalities in a reaction, the substrate bearing the most basic ligand would lead to the predominant product under our reaction conditions. These transformations are believed to proceed via a PdII/IV catalytic cycle. Mechanistic studies implicate that ligand directed palladium mediated C-H activation is the rate-limiting step in these reactions.;Finally, Pd-alkyl intermediates generated via aminopalladation were intercepted using strong oxidants such as PhI(OAc)2 to afford 1,2-difunctionalized products. Under our optimal conditions, the use of alkenes bearing tethered alcohols, acids, or amines led to the formation of substituted tetrahydrofuran rings, lactones, or pyrrolidines. |
