Catalytic Asymmetric Synthesis of 3-(alpha-Hydroxy-beta-carbonyl) Oxindoles by a Sc-III-Catalyzed Direct Aldol-Type Reaction

A direct catalytic asymmetric aldol-type reaction of 3-substituted-2-oxindoles with glyoxal derivatives and ethyl trifluoropyruvate, catalyzed by a chiral N,N'-dioxide Sc(OTf)(3) (Tf=tri-fluoromethancsulfonyl) complex, has been developed that tolerates a wide range of substrates. The reaction proceeds in good yields and excellent enantioselectivities (up to 93 % yield, 99:1 diastereomeric ratio (dr), and >99 % enantiomeric excess (ee)) under mild conditions, to deliver 3-(alpha-hydroxy-(3-carbonyl) oxindoles with vicinal quaternary-tertiary or quatei nary quaternary-stereocenters. Even with 1 mol % catalyst loading or on scaleup (10 mmol of starting material), maintenance of ee was observed, which showed the potential value of the catalyst system. In studies probing the reaction mechanism, a positive no effect was observed and Sc-III-based enolate intermediates were detected by using ESIMS. On the basis of the experimental results and previous reports, a possible catalytic cycle was assumed.