Catalytic enantioselective conjugate addition reactions using chiral Bis(oxazoline) metal complex

Abstract

Catalytic and stereoselective conjugate addition reactions to electron-deficient double bonds is an important organic reaction. In metal-catalyzed conjugate addition reactions, not only bidentates, chelating Michael acceptors are required but also particularly effective metal-substrate coordination is needed for optimum selectivity. $C_2-Symmetric$ Cu(II)-bis(oxazoline) ligands are well-known effective chiral catalysts. In looking for novel substrates, we focused on the suitability of β -ketophosphonates and β -ketosulfones as they are strongly electrophilic and could act as a regiocontrol element for the reaction. Herein we present our results on asymmetric conjugate addition reactions, Friedel-Crafts alkylation, Mukaiyama-Michael reaction, and aza-Michael reactions to α’ -phosphoric enones and α’-sulfonyl enones using chiral Cu(II)-bioxazoline complex. First of all, we studied the asymmetric Friedel-Crafts alkylation of indoles with α’-phosphoric enones using chiral catalyst $[(S)-In-Box]Cu(OTf)_2$. We have been interested in utilizing β -ketophosphonate moieties for chelating to the chiral Lewis acids. The enantioselectivities of the Friedel-Crafts alkylation of indoles to α’ -phosphoric enones were obtained up to 98\% ee. The Friedel-Crafts adducts can be converted into the methyl ketones and α, β -unsaturated ketones by dephosphonylation and the Honer-Emmons reaction. Since the indole skeleton can be used as an important substructure in both natural products and therapeutic agents, this reaction could be an efficient method for the synthetic natural chemistry. Our continuing interest has been focused on the α’ -sulfonyl enones as a good substrate having efficient chelating template for the enantioselective Friedel-Crafts alkylation using $[(S)-In-Box]Cu(OTf)_2$. In most cases, the chemical yields of adducts of the Friedel-Crafts alkylation of indole was good. However, the rate of the reaction and enantioselectivities was not good compared to the α’ -ph...