Origin of the Enantioselectivity in Organocatalytic Michael Additions of β‐Ketoamides to α,β‐Unsaturated Carbonyls: A Combined Experimental,Spectroscopic and Theoretical Study |
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| Authors: | Dr Adrien Quintard Dr Diana Cheshmedzhieva Dr Maria del Mar Sanchez Duque Dr Anouk Gaudel‐Siri Dr Jean‐Valère Naubron Dr Yves Génisson Dr Jean‐Christophe Plaquevent Dr Xavier Bugaut Prof Jean Rodriguez Prof Thierry Constantieux |
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| Institution: | 1. Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille (France). Fax: (+33)?491‐289‐187;2. Aix Marseille Université ‐ CNRS, Institut de Chimie Radicalaire (UMR‐7273), Marseille (France).;3. Present address : Faculty of Chemistry and Pharmacy, University of Sofia, 1164 Sofia (Bulgaria).;4. Spectropole ‐ Aix Marseille Université, 13397, Marseille (France).;5. Université Paul Sabatier ‐ Toulouse III, CNRS, UMR 5068 LSPCMIB, Toulouse (France). |
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| Abstract: | The organocatalytic enantioselective conjugate addition of secondary β‐ketoamides to α,β‐unsaturated carbonyl compounds is reported. Use of bifunctional Takemoto’s thiourea catalyst allows enantiocontrol of the reaction leading either to simple Michael adducts or spirocyclic aminals in up to 99 % ee. The origin of the enantioselectivity has been rationalised based on combined DFT calculations and kinetic analysis. This study provides a deeper understanding of the reaction mechanism, which involves a predominant role of the secondary amide proton, and clarifies the complex interactions occurring between substrates and the catalyst. |
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| Keywords: | density functional calculations enantioselectivity Michael addition organocatalysis reaction mechanisms |
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