M.Sc Thesis

M.Sc StudentHirsch Maayan
SubjectSelective Arylation of Tertiary Amines to N-Aryl Quaternary
Ammonium Salts
DepartmentDepartment of Chemistry
Supervisor ASSOCIATE PROF. Charles E. Diesendruck
Full Thesis textFull thesis text - English Version


N-arylation of tertiary amines to sp3 quaternary ammonium salts is a challenge in organic chemistry. Previous studies on this subject suggested a variety of methods to do so, with the use of heterocycles, phenyl cations, and copper catalysts. However, all these studies require harsh, expensive or unpractical methods, or have a very limited scope, making them undesirable.

A milder arylation approach is to use benzynes to arylate amines. Several studies explore the arylation of tertiary amines, but in all those cases, their goals were in producing an altered tertiary amine, while only using the salt as an unstable intermediate that would undergo a secondary reaction.

In our work, a transition-metal-free procedure for the N-arylation of tertiary amines to sp3 quaternary ammonium salts has been described through the in situ generation of benzyne. Contrary to previous studies, the presented conditions allow for the isolation of various quaternary ammonium salts, including trialkylaryl, dialkyldiaryl and novel triarylalkyl ammonium salts, including N-chiral quaternary ammonium salts, which have potential applications in asymmetric phase-transfer catalysis. The reaction is triggered by the CsF mediated desilylative elimination of triflate, resulting in the benzyne intermediate which undergoes intermolecular nucleophilic attack by tertiary amines to form betaine intermediates. These, in turn, abstract hydrogen from the environment or from a proton donor to stabilize the product, inhibiting dealkylation reactions. This approach is general and works at room temperature, open to air with electron rich or poor benzyne precursors and different tertiary amines, allowing the synthesis of a broad range of N-aryl ammonium salts.