Non-nucleophilic base

As the name suggests, a non-nucleophilic base is an organic base that is a very strong base but at the same time a poor nucleophile. In thermodynamic reaction control an electron donor molecule acts as a nucleophile, in kinetic reaction control the electron donor abstracts a proton (or rather the proton gets harpooned, hence its alternative name harpoon base). For this reason these bases are said to be involved in kinetic deprotonation.

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Non-nucleophilic bases include:

• Lithium diisopropylamide
• Silicon-based amides, such as sodium and potassium bis(trimethylsilyl)amide (NaHMDS and KHMDS respectively)
• Lithium tetramethylpiperidide
• Sodium tert-butoxide

The following diagram shows how the hindered base, lithium diisopropylamide, is used to form to deprotonate an ester to give the enolate in the Claisen ester condensation, instead of undergoing a nucleophilic substitution.