Synthesis of Tetrasubstituted Olefins Through Nucleophilic Addition–Oxidation Cascade Reaction via Base Catalysis

Abstract An efficient addition‐oxidation cascade reaction has been developed between α‐ aminomaleimide and vinylogous oxindole with strong electron‐withdrawing group (‐CN or ‐COCOOR), enabling the synthesis of a diverse array of tetrasubstituted olefins with high yields and exceptional diastereoselectivities (up to 98% yield and up to >20:1 Z / E ). The tolerance of free amine has been investigated, and the results demonstrated that most free amine could not affect the nucleophilic addition step except for aliphatic primary amines. Mechanistic investigations confirmed the formation of an addition intermediate (detected by HRMS), providing key insights into the reaction pathway. Futher study on thermodynamic calculations indicated that the stereoselectivity of oxidation reaction was promoted by generating more thermodynamically stable Z ‐tetrasubstituted olefins. The cascade reactions also proceeded smoothly on large scale, further proving their synthetic value. This strategy, in addition to the authors’ previous work, facilitates substrate‐directed switchable chemodivergent transformations, enhancing synthetic flexibility and broadening potential applications.