The alkylation of unactivated β-methylene C(sp(3))-H bonds of α-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 β,β-hetero-dialkyl- and β-alkyl-β-aryl-α-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 β-disubstituted α-amino acids.
Keywords: CH activation; alkylation; amino acids; palladium; synthetic methods.
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