Overcoming the Necessity of γ‑Substitution in δ‑C(sp3)–H Arylation: Pd-Catalyzed Derivatization of α‑Amino Acids

Despite the emergence of catalytic C­(sp3)–H arylation at the remote δ-position via challenging six-membered ring cyclometalation, the requirement of blocking the more reactive γ-position represents a restricting limitation. The use of the removable N-(2-pyridyl)­sulfonyl directing group provides a viable solution to this challenge, expanding the scope of the Pd-catalyzed δ-C–H arylation of α-amino acid and amine derivatives with (hetero)­aryl iodides. This method is compatible with complex, multifunctional structures at either reaction partner. Experimental and density functional theory studies provide insights about the underlying factors controlling site selectivity.