Synthesis of Ugi 4-CR and Passerini 3-CR Adducts under Mechanochemical Activation

The successful application of a mechanochemical activation strategy that employs high‐speed ball milling (HSBM) conditions for isocyanide‐based multicomponent reactions (IMCRs) was developed. The syntheses of valuable Ugi (by a liquid‐assisted grinding process) and Passerini (under solvent‐free conditions) adducts were achieved by using this method. The protocol disclosed herein allows for the modular synthesis of various compounds according to green chemistry principles, specifically, environmentally friendly conditions, high atom economy, and the absence of toxic byproducts. A mechanochemical activation strategy that uses high‐speed ball milling (HSBM) conditions was applied to isocyanide‐based multicomponent reactions (IMCRs) to yield both Ugi and Passerini adducts. This method allows for a combinatorial synthesis of various compounds by using green chemistry principles (i.e., solvent‐free conditions, high atom economy, absence of toxic byproducts). HSBM = high‐speed ball milling, CR = component reaction.