Mechanochemical transformations have made chemists enter unknown territories, forcing a different chemistry perspective. While questioning or revisiting familiar concepts belonging to solution chemistry, mechanochemistry has broken new ground, especially in the panorama of organic synthesis. Not only does it foster new "thinking outside the box", but it also has opened new reaction paths, allowing to overcome the weaknesses of traditional chemistry exactly where the use of well-established solution-based methodologies rules out progress. In this Review, the reader is introduced to an intriguing research subject not yet fully explored and waiting for improved understanding. Indeed, the study is mainly focused on organic transformations that, although impossible in solution, become possible under mechanochemical processing conditions, simultaneously entailing innovation and expanding the chemical space.This publication is part of a joint Special Collection of Chemistry-Methods and ChemSusChem including invited contributions focusing on "Methods and Applications in Mechanochemistry". Please visit chemsuschem.org/ collections to view all contributions.

Mechanochemical activation of iron cyano complexes by ball milling results in the formation of HCN, which can be trapped and incorporated into α-aminonitriles. This prebiotic impact scenario can be extended by mechanochemically transforming the resulting α-aminonitriles into α-amino amides using a chemical route related to early Earth conditions.

A family of acyclic squaramide receptors (L1-L5) have been synthesised with the aim to bind anions in competitive solvent mixture and to evaluate how the presence of different heteroatoms on...

Discovered over a century ago, Beckmann rearrangement is still today fully compliant with all the green chemistry principles and consistent with the key aspects of sustainable development. Herein, we report on a sustainable mechanochemical procedure allowing the design of new amide frameworks via an eco-efficient “cut-and-paste” process of C–C and C–N bonds on the oxime backbone. We combined inexpensive and readily available reagents, such as p-tosyl imidazole (p-Ts-Im) and oxalic acid, to prepare smoothly and in good to high yields a library of structurally different amides, including value-added marketed compounds such as ε-caprolactam and the active pharmaceutical ingredient (API) paracetamol. This solvent-free mechanochemical procedure has also been optimized and successfully extended to several ketones serving as oxime precursors.

All at once: The simultaneous synthesis and enantioselective functionalization of an indole core is achieved with the assistance of chiral cationic AuI complexes. A range of vinyloxazino‐[4,3‐a]indoles is obtained by a cascade process in a highly enantioselective manner (see scheme; L=chiral diphosphine).