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Updated: Jun 27, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Isothiourea-Catalysed Acylative Dynamic Kinetic Resolution of Tetra-substituted Morpholinone and Benzoxazinone
Haoxiang Zhu1, Alejandro Manchado1,2, Abdikani Omar Farah3
1EaStCHEM, School of Chemistry, University of St Andrews, St Andrews, Fife, KY16 9ST, UK.
Abstract:
The development of methods to allow the selective acylative dynamic kinetic resolution (DKR) of tetra-substituted lactols is a recognised synthetic challenge. In this manuscript, a highly enantioselective isothiourea-catalysed acylative DKR of tetra-substituted morpholinone and benzoxazinone-derived lactols is reported. The scope and limitations of this methodology have been developed, with high enantioselectivity and good to excellent yields (up to 89 %, 99 : 1 er) observed across a broad range of substrate derivatives incorporating substitution at N(4) and C(2), di- and spirocyclic substitution at C(5) and C(6), as well as benzannulation (>35 examples in total). The DKR process is amenable to scale-up on a 1 g laboratory scale. The factors leading to high selectivity in this DKR process have been probed through computation, with an N-C=O⋅⋅⋅isothiouronium interaction identified as key to producing ester products in highly enantioenriched form.
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