Palladium-catalyzed alkylation of unactivated C(sp3)–H bonds with primary alkyl iodides at room temperature: facile synthesis of β-alkyl α-amino acids

Abstract

An efficient protocol for the synthesis of β-alkyl α-amino acids via palladium-catalyzed β-C(sp³)–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 β-alkyl α-amino acid products, including some difficult to access by other means, can be quickly prepared from readily available primary alkyl iodides and alanine precursors.