Mechanochemical activation of metallic lithium for the generation and application of organolithium compounds in air

Abstract

The development of mechanochemical synthetic methods that use ball milling has garnered increased interest in recent years. In organometallic synthesis, this method can eliminate the need for complicated operational set-ups involving inert gases and dry organic solvents, and can enhance reactivity by activating the surface of zero-valent metals. However, the mechanochemical generation of organolithium compounds has not yet been explored despite their widespread use in organic synthesis. Here we report a mechanochemical method for the direct generation of organolithium reagents from readily available organic halides and unactivated lithium metal (lithium wire) under bulk-solvent-free conditions. These reactions rapidly generate a diverse array of organolithium compounds at room temperature without special precautions against moisture and without temperature control. The addition of these compounds to various electrophiles proceeds smoothly in a one-pot fashion. This approach enables reactions with poorly soluble aryl halides and direct C–F bond lithiation that are inefficient under conventional solution-based conditions. (Figure presented.)