Quaternary ammonium salts are stable, safe to handle, and readily prepared by the reaction of amines with excess alkyl electrophiles such as methyl iodide and methyl trifluoromethyl sulfonate. Compared with the corresponding amines, the ammonium salts show much higher C-N reactivity due to strong C-N bond polarity and release of electronically neutral amines in the process of reaction. In addition, quaternary ammonium salts can be prepared from primary, secondary and tertiary amines, whereas diazonium salts and katritzky salts are prepared from only primary amines, and amides are prepared from primary or secondary amines. Hence the transformation method via quaternary ammonium salts is suitable for a wider range of amines. These features make quaternary ammonium salts an attractive electrophilic substrate for various organic transformations.
Quaternary ammonium salts as chemical intermediate is widely used in many reactions, the common reactions are as follows:
- Cross-Coupling Reaction of Aryl Ammonium Salts
The cross-coupling of aryl ammonium salts with aryllithium reagents can be carried out under the similar conditions to those developed by Reeves et al. for the coupling of aryl ammonium salts with aryl Grignard reagents, but requires a higher loading of Pd(PPh3)2Cl2 (5 mol%) and a longer reaction time (12 h). In this reaction, the counter anion of the ammonium salt plays a crucial role in determining the yield of the coupling, and I− is the best. Functional groups including OMe, SiMe3, F, CF3 and acetal groups are tolerated.
Figure 1. Pd-Catalyzed cross-coupling of aryllithium reagents with aryltrimethylammonium iodides.
- Alkylation of Aryltrimethylammonium Triflates Reaction
Ni(dppp)Cl2 was demonstrated to catalyze the alkylation of aryltrimethylammonium triflates with trialkylaluminums. β-Hydrogen-containing alkylaluminum reagents are applicable. The catalyst and reaction conditions were also used for the coupling of triarylaluminums. However, only limited aryltrimethylammonium triflates can be successfully used in this transformation. The Ni(PCy3)2Cl2-catalyzed reaction of ArAlBui2 with aryltrimethylammonium triflates exhibits a wider range of arylammonium salts, affording biaryls in good to excellent yields.
Figure 2. Ni-Catalyzed cross-coupling of aryltrimethylammonium triflates with ArAlBui2.
- Sonogashira Coupling of Terminal Alkynes Reaction
Sonogashira-type coupling between aryltrimethylammonium triflates and terminal alkynes occurs in the presence of ButONa and palladium catalyst. The reaction proceeds under mild conditions with a stoichiometric ratio of reactants. The alkyne substrates with alkyl, aryl, and heteroaryl substituents can be used, and functional groups such as OMe, NHPiv, Cl, F, CF3, and CN are tolerated. DFT calculations reveal that the reaction process involves oxidative addition, alkyne coordination, deprotonation, and C–C reductive elimination.
Figure 3. Mechanism for the palladium-catalyzed coupling of aromatic ammonium salts with terminal alkynes.
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- Wang Z.-X.; et al. Chemical transformations of quaternary ammonium salts via C-N bond cleavage. Org. Biomol. Chem., 2020, 18(6): 1057-1072.