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

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