2,2′-Bipyridine-α,α′-trifluoromethyl-diol ligand: synthesis and application in the asymmetric Et2Zn alkylation of aldehydes

A chiral 2,2 '-bipyridine ligand (1) bearing alpha,alpha '-trifluoromethyl-alcohols at 6,6 '-positions was designed in five steps affording either the R,R or S,S enantiomer with excellent stereoselectivities, i.e. 97% de, >99% ee and >99.5% de, >99.5% ee, respectively. The key step for reaching high levels of stereoselectivity was demonstrated to be the resolution of the alpha-CF3-alcohol using (S)-ibuprofen as the resolving agent. An initial application for the 2,2 '-bipyridine-alpha,alpha '-CF3-diol ligand was highlighted in the Zn-II-catalyzed asymmetric ethylation reaction of aromatic, heteroaromatic, and aliphatic aldehydes. Synergistic electron deficiency and steric hindrance properties of the newly developed ligand afforded the corresponding alcohols in good to excellent yields (up to 99%) and enantioselectivities (up to 95% ee). As observed from single crystal diffraction analysis, the complexation of the 2,2 '-bipyridine-alpha,alpha '-CF3-diol ligand generates an unusual hexacoordinated Zn-II.

Automated summary

By designing a novel chiral ligand, high levels of stereoselectivity can be achieved in synthetic reactions. The unique properties of the new ligand can enhance both reaction yields and enantioselectivities.