Recent Advances in the Synthesis of Spiroindolines: Catalytic Strategies, Stereoselectivity, and Synthetic Utility (2020-2025).

The spiroindoline framework is a privileged scaffold in medicinal chemistry, appearing in natural products and in synthetic bioactive compounds, such as BAY 1214784, RO8994, and RK-287107, with reported activities ranging from antimitotic effects to kinase inhibition. This review covers the methods developed between 2020 and 2025 for constructing spiroindoline frameworks, organized first by the site of spirocyclization (C2 versus C3 of the indole) and then by catalyst class: second- and third-row transition metals, first-row transition metals and main-group Lewis acids, organocatalysis, and visible-light photoredox. For each method we discuss the reaction design, the accessible substrate scope, and mechanistic insights, with particular attention to how stereochemistry is controlled. We also highlight representative downstream transformations that demonstrate the synthetic utility of the produced spiroindolines. Progress over the past five years has been substantial, particularly in enantioselective methods that create a single stereocenter and in cascade designs that build complex polycyclic frameworks in a single operation. Asymmetric construction of multiple adjacent stereocenters, gram-scale demonstrations, and genuinely sustainable conditions remain less developed; these areas are priorities for future work.