As the name suggests, a non-nucleophilic base is a sterically hindered organic base that is a poor nucleophile. Normal bases are also nucleophiles, but often chemists seek the proton-removing ability of a base without any other functions. Typical non-nucleophilic bases are bulky, such that protons can attach to the basic center but alkylation and complexation is inhibited.
A variety of amines and nitrogen heterocycles are useful bases of moderate strength (pK<sub>a</sub> of conjugate acid around 10-13)
Non-nucleophilic bases of high strength are usually anions. For these species, the pK<sub>a</sub>s of the conjugate acids are around 35âÂÂ40.
Other strong non-nucleophilic bases are sodium hydride and potassium hydride. These compounds are dense, salt-like materials that are insoluble and operate by surface reactions.
Some reagents are of high basicity (pK<sub>a</sub> of conjugate acid around 17) but of modest but not negligible nucleophilicity. Examples include sodium tert-butoxide and potassium tert-butoxide.
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.