Acid-Catalyzed Solvent-Switchable Chemoselective N-Alkylation and para C-Alkylation of Unprotected Arylamines...

Nitrogen-containing compounds, such as anilines, represent some of the most prevalent and valuable chemical entities within the field of chemistry. However, their high reactivity, which frequently lacks selectivity, has constrained their application in various chemical transformations, including the alkylation of alcohols. In the present study, we successfully accomplished site-selective para and N-H alkylation of anilines by utilizing ortho-quinone methides under mild conditions. The regioselective para-alkylation was conducted with unprotected anilines in a metal-free environment, while N-H alkylations were effectively performed under similarly mild conditions. DFT calculations were carried out to understand the distinctive chemoselectivity of N-alkylation and C-alkylation of unprotected arylamines with different nonpolar (toluene) and polar protic (HFIP) solvents. Furthermore, the different transition state models identified in our calculations shed light on the intricate interplay between solvent effects and reaction selectivity.