Alkali/alkaline earth metal-mediated mechanochemical Wurtz reactions

Abstract

The Wurtz reaction is a classical C(sp³)–C(sp³) bond-forming reaction involving alkyl halides and alkali metals. However, this reaction generally requires molten or dispersed metals in large amounts of solvent, and has poor functional-group tolerance. Herein, we report a mechanochemical Wurtz reaction by the direct ball-milling of bulk Li, Na, and Ca with haloalkanes. The mechanochemical grinding of these bulk metals with a small amount of a liquid additive (THF) generates highly dispersed reactive metal species, enabling efficient C–C bond formation at room temperature even under air. Under optimized reaction conditions with Li and Na, various primary and secondary haloalkanes are converted into higher-order alkanes. Furthermore, the mechanochemical grinding of Ca is particularly effective for the Wurtz reaction of bromoalkanes bearing various functional groups such as fluoro, chloro, keto, and ester groups, achieving unprecedented C–C coupling and one-step furan synthesis. The developed reaction also allows gram-scale synthesis with a minimal amount of solvent, offering a practical and complementary method to the classical in-solution Wurtz reaction.