Chiral NHC Ligands for the Copper-Catalyzed Asymmetric Conjugate Addition of Grignard Reagents - Archive ouverte HAL
Article Dans Une Revue European Journal of Organic Chemistry Année : 2012

Chiral NHC Ligands for the Copper-Catalyzed Asymmetric Conjugate Addition of Grignard Reagents

Résumé

In this paper, we disclose our recent advances in the copper-catalyzed enantioselective conjugate addition of Grignard reagents to 3-substituted cyclic enones. Several new N-heterocyclic carbene (NHC) ligands have been synthesized in high yields by starting from inexpensive materials. These new NHCs were evaluated as ligands for copper, for the Michaeladdition of ethylmagnesium bromide leading to chiral 3,3-disubstituted cyclohexanones (up to 93 % ee). The best ligand was then engaged in conjugate additions of various Grignard reagents, allowing the formation of quaternary centers with high levels of regio- and enantioselectivity with only 0.75 mol-% catalyst loading. The reaction is also robust to scale-up. The addition of ethylmagnesium bromide for the construction of a 3,3-disubstituted cyclopentanone (up to 86 % ee), a synthetically useful chiral synthon, is noteworthy. A tentative mechanism for the catalytic cycle is also discussed.

Dates et versions

hal-00875360 , version 1 (21-10-2013)

Identifiants

Citer

Nicolas Germain, Magaly Magrez, Stefan Kehrli, Marc Mauduit, Alexandre Alexakis. Chiral NHC Ligands for the Copper-Catalyzed Asymmetric Conjugate Addition of Grignard Reagents. European Journal of Organic Chemistry, 2012, 2012 (27), pp.5301-5306. ⟨10.1002/ejoc.201200479⟩. ⟨hal-00875360⟩
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