Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides

Abstract

Unnatural α- and γ-amino acids display a diverse range of biological activities and serve as crucial intermediates in pharmaceutical production. Specifically, the synthesis of such molecules has been highly sought after in both academia and industry. Nevertheless, their direct synthesis from simple bulk feedstocks has remained largely unexplored, and the switchable synthesis of α- and γ-amino acids through a shared intermediate has never been documented. We disclose herein a four-component reaction involving readily available bulk chemicals to facilitate the switchable synthesis of α- and γ-amino acids from a shared extended p-quinone methide through a tailored amination strategy. A diverse array of amines, including several unmodified drug molecules, along with various other nucleophiles, are readily utilized as suitable substrates in this reaction. We believe this work could inspire future intensive efforts toward the switchable synthesis of amino acids in a practical and efficient manner.