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Updated: Jun 27, 2025
Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
Synthesis of Tetra-Substituted 3-Hydroxyphthalide Esters by Isothiourea-Catalysed Acylative Dynamic Kinetic
Shubham K Agrawal1, Pankaj K Majhi1, Alister S Goodfellow1
1EaStCHEM, School of Chemistry, University of St Andrews, St Andrews, Fife, KY16 9ST, UK.
Abstract:
A general and highly enantioselective method for the preparation of tetra-substituted 3-hydroxyphthalide esters via isothiourea-catalysed acylative dynamic kinetic resolution (DKR) is reported. Using (2S,3R)-HyperBTM (5 mol %) as the catalyst, the scope and limitations of this methodology have been extensively probed, with high enantioselectivity and good to excellent yields observed (>40 examples, up to 99 %, 99 : 1 er). Substitution of the aromatic core within the 3-hydroxyphthalide skeleton, as well as aliphatic and aromatic substitution at C(3), is readily tolerated. A diverse range of anhydrides, including those from bioactive and pharmaceutically relevant acids, can also be used. The high enantioselectivity observed in this DKR process has been probed computationally, with a key substrate heteroatom donor O⋅⋅⋅acyl-isothiouronium interaction identified through DFT analysis as necessary for enantiodiscrimination.
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