Enantioselective Ruthenium-Catalyzed 1,3-Dipolar Cycloadditions between C-Carboalkoxy Ketonitrones and Methacrolein: Solvent Effect on Reaction Selectivity and Its Rational

A catalytic 1,3-dipolar cycloaddition between carboalkoxy ketonitrones and methacrolein under the effect of chiral ruthenium Lewis acid (R,R-1) was developed with high regio-, diastereo-, and enantiocontrol. The diastereochemical outcome of the cyclo addition reaction is marked by a significant solvent effect, and a divergent endo or exo control can be tuned by an appropriate choice of both the solvent and the N- and O-substituents of the ketonitrone. A rationale of the solvent effect, based on the computational study of the interactions between the methacrolein-Ru complex and its counteranion (SbF6-), is proposed to explain the selectivities obtained.