Enabling Site-Selective C-H Functionalization of Aliphatic Alcohols and Amines with exo-Directing Groups by Tether-Tunable Design of Pd^II/Pd^IV Catalysis

We report herein a general platform for palladium catalysis using a library of cyclic diacyl peroxides, achieving site-selective C-H functionalization of aliphatic alcohols and amines. Experimental studies and theoretical calculations indicate that bystanding cyclic diacyl peroxides minimize unwanted reductive elimination events and enable controlled C-H cleavage. The protocol is simple and scalable and offers high selectivity and a broad range of substrates and nucleophiles, including complex molecules. The findings advance understanding of high-valent palladium chemistry, providing a tool for creating chemically diverse vicinal diols and amino alcohols and opening new possibilities in C-H functionalization.