Chiral Zn(II)-Bisamidine Complex as a Lewis-Brønsted Combined Acid Catalyst: Application to Asymmetric Mukaiyama Aldol Reactions of <em>α</em>-Ketoesters

Abstract

Focusing on the steric and electronic properties of the resonance-stabilized amidine framework, a cationic metal-bisamidine complex was designed as a conjugated combined Lewis-Brønsted acid catalyst. The chiral Zn(II)-bisamidine catalyst prepared from the 2,2'-bipyridyl derived bisamidine ligand, ZnCl₂, and AgSbF₆ promoted asymmetric Mukaiyama aldol reaction of <em>α</em>-ketoester and <em>α</em>,<em>α</em>-disubstituted silyl enol ether to afford the <em>α</em>-hydroxyester having sequential quarternary carbons in good yield, albeit with low enantioselectivity. Addition of 1.0 equivalent of the fluoroalcohol having suitable acidity and bulkiness dramatically increased the enantioselectivity (up to 68% <em>ee</em>). DFT calculations suggested that this additive effect would be caused by self-assembly of the fluoroalcohol on the Zn(II)-bisamidine catalyst.

Keywords

• Lewis-Brønsted combined acid
• bisamidine
• asymmetric Mukaiyama aldol reaction
• &lt;em&gt;α&lt;/em&gt;-ketoester