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Synthetic Methodology for Asymmetric Ferrocene Derived Bio-conjugate Systems via Solid Phase Resin-based Methodology
Published on: March 12, 2015
Synthesis of Anti-β-Hydroxytryptophans by Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution
Scott R Pollack1, Michael R Berwanger1, Sylvie L Pailloux1
1Department of Process Research & Development, Merck & Co, Inc., Rahway, NJ 07065, United States.
Abstract:
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.
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