Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• ). Interestingly, a satisfactory result (89% yield and >99% ee) was also obtained when the reaction was performed on a 7.0 mmol scale using 15% of catalyst loading. Similarly, Chen and co-workers reported that β-ICD, as a bifunctional catalyst, can also efficiently catalyze the MBH reactions of 7-azaisatins with

• maleimides, affording the corresponding products in excellent yields (up to 98% yield) and with excellent enantioselectivity (up to 94% ee, Scheme 37) [54]. Additionally, other activated alkenes such as methyl and ethyl acrylates and acrolein reacted smoothly with 7-azaisatins, giving the corresponding

• products in excellent yields and with excellent enantioselectivity. The authors found that 7-azaisatins are better electrophiles than isatins and could be used for accessing biologically important isatin analogs. In 2015, Ren et al. developed a novel quinidine catalyst (cat. 23) bearing a 2-aminopyrimidin

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• in diverse biologically active substances. Here 7-azaisatins turned out to be more efficient electrophiles than the analogous isatins in the enantioselective Morita–Baylis–Hillman (MBH) reactions with maleimides using a bifunctional tertiary amine, β-isocupreidine (β-ICD), as the catalyst. This route

• allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee). Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized. Keywords: 7-azaisatins; β-isocupreidine; bifunctional catalysis; maleimide; MBH

• , all these cases suffered from low reactivity and long reaction times were always required (usually > 48 h) for better conversions. 7-Azaisatins bearing an additional nitrogen atom at the 7-position of the 2-oxindole scaffold might be better electrophiles than isatins owing to the electron-withdrawing