Accessing the less traveled path: Regioselective synthesis of 3-oxindoles

Abstract

Indoxyls, commonly known as 3-oxindoles, are privileged heterocyclic scaffolds found in natural products, bioactive molecules, and functional materials. Despite their close structural relationship to 2-oxindoles, selective access to 3-oxindoles, particularly 2-functionalized variants remains significantly more challenging, making regioselective control a central synthetic issue. While methods for constructing 3-functionalized 2-oxindoles are well established, the synthesis of indoxyl frameworks has emerged as a rapidly expanding and conceptually distinct area of research. This review traces the advances made in twenty-first century in the construction of 3-oxindole frameworks, emphasizing regioselective and asymmetric strategies. Developments in metal catalysis, organocatalysis, photocatalysis, electrocatalysis, and hypervalent iodine chemistry are discussed, showcasing approaches to C2-functionalization, spirocyclization, and dimerization. Collectively, these advances demonstrate the growing potential of indoxyl chemistry to expand chemical space and inspire future developments in synthesis and total synthesis.