We optimized the structure of a new family of chiral diarylprolinol-type organocatalysts with improved performances in conjugate addition reactions performed in water and proceeding under the iminium activation manifold. The principles behind the catalyst design were, firstly, the incorporation of a tertiary amino group at the 4-position of the pyrrolidine scaffold, which can facilitate the reaction by providing a basic site that favors deprotonation of the pronucleophile, and, secondly, a bulky diaryltrialkylsilyloxymethyl group maintained at the 2-position to control the iminium ion geometry and to provide the required steric bias for face stereoselection. The nature of this 4-dialkylamino group and the relative 2,4-configuration was optimized and the resulting catalyst proved its efficiency in the catalytic enantioselective cyclopropanation of α,β-unsaturated aldehydes using water as the reaction solvent. Moreover, the reaction was studied by computational methods, which indicated that the overall transformation proceeded through a cascade Michael/α-alkylation sequence, in which the first iminium-mediated Michael addition reaction was the rate-determining step and also the step at which stereochemical information was transferred from the catalyst to the products.
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