Advances of KO <i>t</i> Bu‐Involved Reactions in Organic Synthesis From 2020 to 2025

Potassium tert-butoxide (KOtBu), a strong non-nucleophilic base with a pKa value of 17.5, has emerged as a versatile and indispensable reagent in modern organic synthesis. Notably, KOtBu can promote a wide range of bond-forming transformations that conventionally rely on transition-metal catalysis, enabling the efficient construction of carbon-carbon (CC), carbon-heteroatom (CX), and heteroatom-heteroatom (XY) bonds under relative mild reaction conditions. KOtBu-mediated reactions predominantly proceed via two well-established mechanistic pathways, namely ionic and radical manifolds, wherein the reactivity of key intermediates is highly dependent on reaction conditions and exogenous additives. Compared to transition-metal catalysts, KOtBu offers prominent advantages in terms of economic cost and environmental compatibility. In this review, we systematically summarize recent advances in KOtBu-involved reactions, covering the construction of carbon-carbon (CC), carbon-nitrogen (including CN and CONH), carbon-oxygen (CO), carbon-silicon (CSi), as well as miscellaneous bonds including carbon-sulfur (CS), carbon-seleno (CSe), carbon-iodo (CI), carbon-deuterium (CD), etc. We focus on reaction development, plausible mechanistic pathways, and potential synthetic applications of these protocols in the synthesis of pharmaceuticals, agrochemicals, and functional materials. This review aims to provide an up-to-date overview of KOtBu-enabled organic transformations for organic, medicinal, and materials chemists, and to facilitate further exploration and expansion of their synthetic utility.