Chiral ruthenium Lewis acid-catalyzed nitrile oxide cycloadditions

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][SbF₆], 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.