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(sp(3))-H arylation at the remote delta-position via challenging six-membered ring cyclometalation, the requirement of blocking the more reactive gamma-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 delta-C-H arylation of a-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.

Automated summary

The use of a removable N-(2-pyridyl)sulfonyl directing group provides a viable solution to overcome the limitation of blocking the more reactive gamma-position, allowing for the expansion of the scope of Pd-catalyzed delta-C-H arylation. This method is compatible with complex, multifunctional structures at either reaction partner. Experimental and density functional theory studies offer insights into the factors controlling site selectivity.