pronucleophile

A pronucleophile is a substrate that is not a nucleophile in its ground state but can become nucleophilic upon activation. In organic chemistry, pronucleophiles are precursors to nucleophiles: they are typically neutral or weakly reactive and require a triggering step to generate a reactive carbon-centered species, such as an enolate or carbanion, that can attack an electrophile. Activation methods commonly include coordination to a Lewis acid or deprotonation by a base, which reveals the latent nucleophilic site.

In practice, pronucleophiles enable reactions where the nucleophilic character is formed in situ, providing a route to modulate reactivity and stereoselectivity. A classic example is silyl enol ethers, which act as pronucleophiles in Mukaiyama-type aldol reactions. Upon activation with a Lewis acid like BF3·OEt2 or TiCl4, they generate enolate-like nucleophiles that attack carbonyl compounds. Other latent or masked nucleophiles, such as certain enol silanes or allyl-derived pronucleophiles, can similarly be activated to reveal their nucleophilic centers.

The concept of pronucleophiles helps chemists conceptualize and design reactions where a reactive nucleophile is produced only after an activation step, allowing careful control over reactivity and selectivity. It is closely associated with enolate chemistry and Lewis acid–catalyzed transformations in organic synthesis.