Solid-state reactions using mechanochemical activation have emerged as solvent-free atom-efficient strategies for sustainable chemistry. Herein we report a new mechanochemical approach for the amide

An expansion of the solvent‐free synthetic toolbox is essential for advances in the sustainable chemical industry. Mechanochemical reactions offer a superior safety profile and reduced amount of waste compared to conventional solvent‐based synthesis. Herein a new mechanochemical method was developed for nucleophilic substitution of alcohols using fluoro‐N,N,N′,N′‐tetramethylformamidinium hexafluorophosphate (TFFH) and K2HPO4 as an alcohol‐activating reagent and a base, respectively. Alcohol activation and reaction with a nucleophile were performed in one milling jar via reactive isouronium intermediates. Nucleophilic substitution with amines afforded alkylated amines in 31–91 % yields. The complete stereoinversion occurred for the SN2 reaction of (R)‐ and (S)‐ethyl lactates. Substitution with halide anions (F−, Br−, I−) and oxygen‐centered (CH3OH, PhO−) nucleophiles was also tested. Application of the method to the synthesis of active pharmaceutical ingredients has been demonstrated.

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Herein, we present a new strategy for the preparation of a broad range of brassinosteroid biosynthetic precursors/metabolites differing by the ring A fragment. The protocol is based on the use of readily available phytohormones of this class bearing a 2α,3α-diol moiety (epibrassinolide or epicastasterone) as starting materials. The required functionalities (Δ2-, 2α,3α- and 2β,3β-epoxy-, 2α,3β-, 2β,3α-, and 2β,3β-dihydroxy-, 3-keto-, 3α- and 3β-hydroxy-, 2α-hydroxy-3-keto-) were synthesized from 2α,3α-diols in a few simple steps (Corey–Winter reaction, epoxidation, oxidation, hydride reduction, etc.).