Stereoselective synthesis of CF3-containing spirocyclic-oxindoles using N-2,2,2-trifluoroethylisatin ketimines: an update

Abstract

The introduction of fluorine-containing groups into organic molecules either changes or improves the characteristics of the target compounds. On the other hand, spirocyclic-oxindoles featuring C-3 functionalized sp³-hybridized carbon atoms of three-dimensional orthogonally shaped molecules were well recognized in the core structure of varied natural products and synthetic pharmaceutical targets. Consequently, the construction of spirooxindoles by an elegant synthetic approach with efficient stereocontrol has received tremendous interest over the past decades. In this context of the synergic combination of the features associated with fluorine-containing compounds and the synthetic and medicinal efficiency associated with spirooxindoles, the stereodivergent installation of CF₃ groups embedded with spirooxindoles is of increasing academic and scientific interest. This mini-review article is dedicated to demonstrating a critical overview of the recent stereoselective synthesis of spirocyclic-oxindoles featuring trifluoromethyl groups by employing the reactivity of N-2,2,2-trifluoroethylisatin ketimines as an efficient and easily prepared synthon, and covers the literature reports from 2020 to date. Besides exploring the advancements accomplished in this area, we also investigate the limitations associated with reaction discovery, mechanistic rationalization, and future applications.