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 selectivityWe thank the Ministerio de Economía, Industria y Competitividad (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER, UE) (Project CTQ2015-66954-P) and Ministerio de Ciencia e Innovación (MICINN)/FEDER, UE (Agencia Estatal de Investigación/Project PGC2018- 098660-B-I00) for the financial suppor