Mechanochemical Pd‐Catalyzed Cross‐Coupling of In‐Situ Generated Reformatsky Zn‐Enolates

Abstract Transition‐metal‐catalyzed α‐arylations of carbonyl compounds have shown to be a useful strategy for the late‐stage synthesis of α‐arylesters. However, the use of strong basic conditions and difficult handling necessary for the in‐situ preparation of enolates is a major disadvantage. On the other hand, using Reformatsky zinc‐enolates can overcome these challenges. Moreover, mechanochemical in‐situ activation of zinc is even more beneficial. Herein, we report mechanochemical Pd‐catalyzed cross‐coupling between in‐situ generated Reformatsky Zn‐enolates and aryl halides. This operationally simple procedure affords α‐arylated esters or amides using an affordable catalytic system. Reactions were carried under air and ambient conditions using granulated zinc without the need for its pre‐activation. Less reactive and commercially more affordable aryl bromides afforded the desired products in good to excellent yields in comparison to aryl iodides. The optimized conditions were applied in scale‐up reaction and in the synthesis of α‐arylated esters, amides, and derivatives of natural products.