Palladium-Catalyzed PIDA-Mediated δ-C(sp 3 )-H Acetoxylation of Amino Acid Derivatives: Overriding Competitive Intramolecular Amination.

The selective δ-C(sp 3 )-H acetoxylation of N-(SO 2 Py)-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 SO 2 Py 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-CH 2 . Experimental and DFT mechanistic studies provide important insights about the mechanism and the underlying factors controlling the chemo- and regioselectivity.