One-pot and sequential asymmetric hydrogenation of β,δ-diketoesters into functionalized 1,3-diols:: From anti- to syn-stereoselectivity

The asymmetric hydrogenation of methyl 3,5-dioxohexanoate (1) into mixtures of 3,5-dihydroxyesters (2) and 3-hydroxylactones (3) has been reinvestigated with a variety of ruthenium catalysts. Catalysts bearing diphosphanes which possess axial chirality such as (S)-MeO-Biphep give predominantly (3R,5S)-anti-2 in up to 78% de and 95% ee, affording an efficient synthesis of (S)-6-methyl-5,6-dihydro-2-pyrone [(S)-5] in up to 95% enantiomeric excess. On the contrary, some Ru-{amidophosphane-phosphinite} complexes catalyze sluggishly the formation of syn-2 in up to 92% de but with poor enantiomeric excesses. In all cases, methyl (R)-3-hydroxy-5-oxohexanoate [(R)-11] is the exclusive primary hydrogenation product, which can be isolated in high yields and enantiomeric excesses up to 78%. Further hydrogenation of enantiomerically enriched (R)-11 in a separate experiment affords (3R,5R)-syn-2 in high diastereomeric and enantiomeric excesses (up to 80% and 98%, respectively), provided a Ru-(R)-Binap-type catalyst is used.