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 = 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.
Shen
Ke
K
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China.
Liu
Xiaohua
X
Zheng
Ke
K
Li
Wei
W
Hu
Xiaolei
X
Lin
Lili
L
Feng
Xiaoming
X
D002384:Catalysis; D056831:Coordination Complexes / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008698:Mesylates / Q000737:chemistry; D000078183:Oxindoles; D012538:Scandium / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
D056831:Coordination Complexes; D007211:Indoles; D008698:Mesylates; D000078183:Oxindoles; C022960:2-oxindole; C012077:trifluoromethanesulfonic acid; D012538:Scandium