Asymmetric Synthesis of Small Molecule Inhibitors of IL-17A via Crystallization-Induced Diastereoselective Strecker Reaction

Crystallization-induced asymmetric transformations can dramatically alter the product ratio from a reaction with inherently poor or undesired selectivity. Reported herein is a rare example of a dynamic crystallization-induced diastereoselective Strecker reaction which overrides the inherent substrate bias in the preparation of aryl-substituted tetrahydrofuran-derived non-natural amino acids. Discovery of a new non-hydrogenative auxiliary cleavage method enables application of the Strecker reaction to the large-scale syntheses of small molecule inhibitors of IL-17A.