Secondary Amine‐Catalyzed Asymmetric γ‐Alkylation of α‐Branched Enals via Dienamine Activation |
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Authors: | Mattia Silvi Carlo Cassani Antonio Moran Paolo Melchiorre |
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Institution: | 1. ICIQ – Institute of Chemical Research of Catalonia, Avenida Pa?sos Catalans 16 ‐ ES‐43007 Tarragona, (phone: +34?977?920?807);2. ICREA – Institució Catalana de Recerca i Estudis Avan?ats, Passeig Lluís Companys 23 – ES‐08010 Barcelona |
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Abstract: | The direct and enantioselective γ‐alkylation of α‐substituted α,β‐unsaturated aldehydes proceeding under dienamine catalysis is described. We have found that the Seebach modification of the diphenyl‐prolinol silyl ether catalyst in combination with saccharin as an acidic additive promotes an SN1 alkylation pathway, while ensuring complete γ‐site selectivity and a high stereocontrol. Theoretical and spectroscopic investigations have provided insights into the conformational behavior of the covalent dienamine intermediate derived from the condensation of 2‐methylpent‐2‐enal and the chiral amine. Implications for the mechanism of stereoinduction are discussed. |
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Keywords: | Enantioselective synthesis Aldehydes α ‐substituted α β ‐unsaturated Organocatalysis Dienamine activation Secondary amine Alkylation X‐Ray crystallography |
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