Herein we disclose an efficient and experimentally straightforward method for the stereoselective synthesis of a variety of α‐substituted Mannich salts. This direct three‐component Mannich reaction operates on readily available reagents in almost stoichiometric ratio and enables the preparation of both enantiomers. Crystallization controlled epimerization allows isolation of the target compounds in high enantio‐ and diastereomeric purities by a simple filtration. The efficiency of this chromatography‐free approach predestines it for the gram‐scale synthesis and industrial applications.
An intriguing example of a crystallization‐induced stereochemical switch in the configuration of aza‐Michael reaction products is described. Depending on both the stereochemical purity and stoichiometric ratio of the chiral amine used, the reaction delivers crystalline diastereomers of a different stereochemistry. The optically pure diastereomer smoothly converts to its racemic epimer salt upon the addition of a complementary chiral amine.
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