Advances in Mechanochemical Methods for One-Pot Multistep Organic Synthesis

Mechanochemical synthesis has emerged as a powerful and more sustainable alternative to conventional solution-based methods, offering advantages such as no or only minimal solvent use, reduced reaction times, and simplified operational conditions. The integration of multiple steps into a single reaction vessel further enhances these benefits by eliminating workup and purification steps, reducing waste, and often improving overall efficiency. This review highlights recent advancements in mechanochemical one-pot multistep reactions in organic synthesis, focusing on protocols with sequential one-pot operation. Diverse transformations are covered, including heterocycle formation, functional group interconversions, and the synthesis of active pharmaceutical ingredients, while discussing both the operational and environmental advantages of these methodologies, along with their remaining challenges. Overall, mechanochemical one-pot synthesis has the potential to streamline transformations and therefore contribute to more sustainable approaches in modern organic synthetic chemistry.