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.

Non-nucleophilic bases include:

Moderate Basicity (pKa of conjugate acid around 10-13)

• Carbonate Salts, K₂CO₃ and for better solubility in organic solvents Cs₂CO₃ -- a favorite for cross-coupling reactions.
• Triethylamine, or TEA
• N,N-Diisopropylethylamine, or DIPEA (also called Hünig's Base)
• 1,8-Diazabicycloundec-7-ene, or DBU—a favorite for the E2 elimination reaction.

High Basicity (pKa of conjugate acid around 17)

• Sodium tert-butoxide
• Potassium tert-butoxide

Great Basicity (pKA of conjugate acid around 35-40)

• Tert-Butyllithium
• Sodium hydride
• Lithium diisopropylamide, or LDA
• Silicon-based amides, such as sodium and potassium bis(trimethylsilyl)amide (NaHMDS and KHMDS respectively)
• Lithium tetramethylpiperidide, or LiTMP

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

This reaction (deprotonation with LDA) is commonly used to generate enolates.