Palladium-catalyzed alkylation of unactivated C(sp(3))-H bonds with primary alkyl iodides at room temperature: facile synthesis of beta-alkyl alpha-amino acids

An efficient protocol for the synthesis of beta-alkyl alpha-amino acids via palladium-catalyzed beta-C(sp(3))-H alkylation of aminoquinoline-coupled phthaloyl alanine is developed. The new TFA-promoted reaction conditions provide excellent C-H alkylation reactivity with alkyl iodides bearing moderately electron-withdrawing groups at room temperature. A range of beta-alkyl alpha-amino acid products, including some difficult to access by other means, can be quickly prepared from readily available primary alkyl iodides and alanine precursors.