Sulfonamide-Promoted Palladium(II)-Catalyzed Alkylation of Unactivated Methylene C(sp3)-H Bonds with Alkyl Iodides

The alkylation of unactivated beta-methylene C(sp(3))-H bonds of alpha-amino acid substrates with a broad range of alkyl iodides using Pd(OAc)(2) as the catalyst is described. The addition of NaOCN and 4-Cl-C6H4SO2NH2 was found to be crucial for the success of this transformation. The reaction is compatible with a diverse array of functional groups and proceeds with high diastereoselectivity. Furthermore, various beta,beta-hetero-dialkyl-and beta-alkyl-beta-aryl-alpha-amino acids were prepared by sequential C(sp(3))-H functionalization of an alanine-derived substrate, thus providing a versatile strategy for the stereoselective synthesis of unnatural beta-disubstituted alpha-amino acids.