Recent advances in the synthesis of 3-aryl-3-hydroxy-2-oxindoles
Xiao-Ju Si1, Qianqian Ren1, Teck-Peng Loh1,2
1College of Advanced Interdisciplinary Science and Technology, Henan University of Technology, Zhengzhou, 450001, China. caist_sxj@haut.edu.cn.
Abstract:
3-Aryl-3-hydroxy-2-oxindole is a bioactive chiral core widely distributed in natural alkaloids and drug candidates. Its biological activity is largely determined by the substitution and stereochemistry at the C3 quaternary carbon. In this review, five mainstream synthetic strategies toward 3-hydroxyoxindoles are summarized, including nucleophilic addition of various nucleophiles to isatins, intramolecular cyclization of α-ketoamides, direct C3 oxidative hydroxylation of indole/oxindole, one-pot tandem cyclization of acyclic aniline-derived substrates, and cyclization of heteroatom-substituted aromatics such as nitroarenes and α-diazoamides. Each route is systematically discussed in terms of catalytic systems, reaction mechanisms, substrate compatibility and stereocontrol performance. The merits and subtle limitations of metal catalysis, photoredox, electrochemistry and transition-metal-free protocols are comparatively analyzed. Current bottlenecks and future directions for economical, highly enantioselective synthesis of such privileged scaffolds are outlined to support related pharmaceutical and synthetic research.
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