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

The selective delta-C(sp(3))-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 delta-site selectivity predominates over traditionally more favorable 5-membered cyclopalladation at competitive gamma-CH2. Experimental and DFT mechanistic studies provide important insights about the mechanism and the underlying factors controlling the chemo- and regioselectivity.

Automated summary

The selective delta-C(sp(3))-H acetoxylation of N-(SO2Py)-protected amino acid derivatives has been achieved using palladium-catalysis and PhI(OAc)(2) as both oxidant and acetoxy source. The unique structural and electronic features of SO2Py are crucial in overriding the more favorable intramolecular C-H amination.