Asymmetric α-amination of aldehydes at low catalytic loading: application to the synthesis of solriamfetol and nateglinide

Abstract

We report an asymmetric α-amination of aldehydes using a nonsilyl bicyclic secondary amine organocatalyst at 0.1 mol % in the presence of propanoic acid (100 mol %). Catalyst stability toward dibenzyl azodicarboxylate is investigated by 1 H NMR spectroscopy under varying acid loadings. This method exhibits a broad substrate scope, affording products in up to 96% yield and 94% ee. This scalable methodology is applied to the concise asymmetric synthesis of solriamfetol and nateglinide.