Access to Unnatural α-Amino Acids via Visible-Light-Mediated Decarboxylative Conjugate Addition to Dehydroalanine

Abstract

An expedient synthesis of β-alkyl α-amino acids is reported via application of decarboxylative photocatalysis. The method utilizes abundant, diverse, and inexpensive carboxylic acids to provide radicals for conjugate addition to dehydroalanine ester. High-throughput experimentation revealed an acridinium-based photocatalyst, tetraMeO-Acri-N-diMeOPh, to be the optimal choice enabling a general method that is tolerant to a wide range of functional groups. A scalable batch protocol and a parallel library synthesis for accessing diverse unnatural α-amino acids are described.