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 (pKa of conjugate acid
Non-nucleophilic bases of high strength are usually anions. For these species, the pKas of the conjugate acids are around 35–40.
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.