Palladium-Catalyzed PIDA-Mediated δ-C(sp3)−H Acetoxylation of Amino Acid Derivatives: Overriding Competitive Intramolecular Amination

Abstract

The selective δ-C(sp3)−H acetoxylation of N-(SO2Py)-protected amino acid derivatives has been accomplished by using palladium-catalysis and PhI(OAc)2 (PIDA) as both terminal oxidant and acetoxy source. The distinct structural and electronic features of the SO2Py compared to more traditional carbonyl-based directing groups is essential to override the otherwise more favourable competitive intramolecular C−H amination. The δ-site selectivity predominates over traditionally more favorable 5-membered cyclopalladation at competitive γ-CH2. Experimental and DFT mechanistic studies provide important insights about the mechanism and the underlying factors controlling the chemo- and regioselectivity.