Synfacts 2011(8): 0904-0904  
DOI: 10.1055/s-0030-1260840
Organo- and Biocatalysis
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric Michael Addition of α-Substituted β-Keto Amides

Contributor(s): Benjamin List, Manuel Mahlau
M. del Mar Sanchez Duque, O. Baslé, N. Isambert, A. Gaudel-Siri, Y. Génisson, J.-C. Plaquevent, J. Rodriguez*, T. Constantieux*
Aix-Marseille Université and Université Paul Sabatier Toulouse III, France
Further Information

Publication History

Publication Date:
20 July 2011 (online)

Significance

Rodriguez, Constantieux and coworkers report the enantioselective organocatalytic Michael addition of α-substituted β-keto amides to enones leading to all-carbon quaternary stereocenters. The reaction is catalyzed by a bifunctional amino-thiourea (A). In the proposed transition state the enolate resulting from α-deprotonation of the β-keto amide is stabilized by hydrogen bonding to the thiourea scaffold, while the ammonium form of the catalyst’s amine binds to the amide oxygen. These interactions block the si-face of the enolate leading to Michael addition via the re-face. When acrolein was used as electrophile spontaneous spiro-hemiacetalization was observed. After oxidation the corresponding spiro-imide was obtained with high enantioselectivity.