Chiral ruthenium Lewis acid-catalyzed nitrile oxide cycloadditions

Abstract

The synthesis of the chiral ligand ( R, R)-BIPHOP-F is detailed. Its coordination to a cationic cyclopentadienyl ruthenium fragment generates [Ru (acetone)( R, R)-BIPHOP-F)Cp][SbF 6], a transition metal Lewis acid that catalyzes the [3+2] dipolar cycloaddition reaction between aryl nitrile oxides and α,β-unsaturated aldehydes to give chiral 2-isoxazolines with yields of 43–98% and asymmetric purity of 60–93% ee. The stereochemistry of the major enantiomer is S, consistent with an approach of the nitrile oxide to the C α- Si face of the enal in the anti- s- trans conformation in the catalyst site.