Organocatalytic Stereoselective Synthesis of 3-Alkyl-3-hydroxy-2-oxindoles Catalyzed by Novel Water-compatible Axially Unfixed Biaryl-based Bifunctional Organocatalysts

In this work, six novel axially unfixed biaryl‐based water‐compatible bifunctional organocatalysts were designed and synthesized for the organocatalytic access to a variety of 3‐alkyl‐3‐hydroxy‐2‐oxindole derivatives via aldol reactions in water. Organocatalyzed by 5a, the direct aldol reactions of isatins with enolisable ketones underwent readily in water, furnishing the structurally diverse 3‐alkyl‐3‐hydroxy‐2‐oxindoles in various stereoselectivities (up to>99% dr and >99% ee). Moreover, a plausible transition state of the conducted aldol reactions was hypothesized to shed light on the observed stereoselectivities of the obtained 3‐alkyl‐3‐hydroxy‐2‐oxindoles. Catalyzed by axially unfixed biaryl‐based bifunctional organocatalys 5a, the direct aldol reactions of isatins with ketones provided a variety of 3‐alkyl‐3‐hydroxy‐2‐oxindole derivatives in high chemical yields (up to >99%) with excellent stereoselectivities (up to >99:1 dr and >99% ee).