Access to Hetero-Benzyl Scaffolds via Transient-Ligand-Enabled Direct γ-C(sp3)-H Arylation of 3-Methylheteroarene-2-Carbaldehydes.

An efficient and straightforward method has been developed for the synthesis of β-benzyl-substituted 5-membered heterocyclic carbaldehydes via transient directing-group-enabled direct γ-C(sp3)-H arylation of 3-methylheteroarene-2-carbaldehydes. A wide range of 3-methylheteroarene carbaldehydes undergo coupling with a variety of aryl iodides, including less reactive iodo pyridine derivatives to provide a library of highly selective functionalized products in good to excellent yields. Some of these products have been successfully utilized in synthesizing useful synthetic intermediates.