Synthesis of Anti-β-Hydroxytryptophans by Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution

A general approach to anti-β-hydroxytryptophans via the corresponding α-amino-β-keto esters through a Ru-catalyzed asymmetric transfer hydrogenation-dynamic kinetic resolution (ATH-DKR) cascade is described. The requisite starting materials are prepared through a robust, scalable, and chromatography-free three-step approach from indole-3-carboxylic acids. A thorough HTE screening/optimization of the ATH-DKR reaction, with regard to protecting groups and substitution patterns, was undertaken to prepare an array of analogs in very good yields and with high enantio- and diastereoselectivity.