Abstract
The N-arylation of tertiary amines to provide sp3 quaternary ammonium salts is a challenge in organic chemistry. To date, no general
method for such arylations has been established. Here, we summarize a variety of strategies
that have been tested, starting with harsh nucleophilic aromatic substitutions, through
to the use of copper catalysis and the application of strong electrophiles, such as
phenyl cations and benzynes. The achievements and limitations of each method are summarized,
and the challenges yet to be met in the synthesis of charged ammonium compounds are
described.
1 Introduction
2 Alkylation of Anilines: The Menshutkin Reaction
3 Arylations
3.1 Nucleophilic Aromatic Substitutions by Tertiary Amines
3.2 Preparation of N-Arylpyridinum Salts from Zincke and Pyrylium Salts
3.3 Arylations Using Phenyl Cations
3.4 Copper-Catalyzed Arylation of N-Heteroarenes
3.5 Benzynes as Aryl Electrophiles
4 Conclusions and Perspective
Key words
arylation - quaternary ammonium salts - benzyne chemistry - copper catalysis - nucleophilic
aromatic substitution - phenyl cations - Menshutkin reaction - Zincke reaction
