Metal‐Catalyzed Organic Reactions by Resonant Acoustic Mixing**
Lori Gonnet, Cameron B. Lennox, Jean‐Louis Do, Ivani Malvestiti, Stefan G. Koenig, Karthik Nagapudi, Tomislav Friščić
Abstract
Abstract We demonstrate catalytic organic synthesis by Resonant Acoustic Mixing (RAM): a mechanochemical methodology that does not require bulk solvent or milling media. Using as model reactions ruthenium‐catalyzed ring‐closing metathesis and copper‐catalyzed sulfonamide‐isocyanate coupling, RAM mechanosynthesis is shown to be faster, operationally simpler than conventional ball‐milling, while also providing the first example of a mechanochemical strategy for ruthenium‐catalyzed ene‐yne metathesis. Reactions by RAM are readily and directly scaled‐up without any significant changes in reaction conditions, as shown by the straightforward 200‐fold scaling‐up of the synthesis of the antidiabetic drug Tolbutamide, from hundreds of milligrams directly to 30 grams.