Catalytic asymmetric synthesis of 3-(alpha-hydroxy-beta-carbonyl) oxindoles by a Sc(III)-catalyzed direct aldol-type
Ke Shen1, Xiaohua Liu, Ke Zheng
1Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China.
Abstract:
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 = trifluoromethanesulfonyl) 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-beta-carbonyl) oxindoles with vicinal quaternary-tertiary or quaternary-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 nonlinear 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.
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