Tuning diastereoselectivity with the solvent: the asymmetric hydrogenation of simple and functionalized 1,3-diketones with ruthenium(amidophosphine–phosphinite) catalysts

Abstract

Spectacular solvent effects in the asymmetric hydrogenation of methyl 3,5-dioxohexanoate (3) and 2,4-pentanedione (5) have been observed using Ru[(S)-Ph,Ph-oxoProNOP]X₂ complexes (X=η³-C₄H₇, IIa; CF₃CO₂, IIb; (R)-MTPA, IIc) as catalyst precursors. β-Diketones 3 and 5 are respectively reduced to the corresponding β-diols 4 and 6. In both cases, an almost complete reversal in the diastereoselectivity of the reaction is observed when changing the solvent from CH₂Cl₂ (syn-4 in up to 92% de; meso-6 in up to 84% de) to a 1:1 CH₂Cl₂–CH₃OH mixture (anti-4 and anti-6 in up to 84% de). The extent of this solvent effect is much less marked with Ru-atropisomeric diphosphine catalysts.