Al(OTf)₃ catalyzed adamantylation of N-nucleophiles

Various adamantylated nitrogen-containing compounds are known primarily as substances exhibiting antiviral properties. Along with the well-known and sufficiently studied adamantyl-containing amines - amantadine and rimantadine, antiviral activity is manifested by representatives of such types of compounds as adamantylated azoles, amides, sulfamides, urethanes, and a number of other. In addition, adamantylated nitrogen-containing compounds are interesting as intermediates for the synthesis of other compounds with practically significant properties. Known methods for obtaining such compounds are usually bases on the adamantylation of various N-nucleophiles by 1-halogen adamantanes or 1-adamantanol, in the presence of Lewis or Brønsted acids, i.e. in conditions that ensure the generation of 1-adamantyl cation. Despite the diversity of the existing methods of adamantylation, most of them have a number of significant drawbacks, which include non-stoichiometric use of reactants (a double or triple excess of one of the reactants is often used). Some catalysts or reagents used in these reactions are aggressive or highly toxic substances, which makes such methods inconsistent with the principles of "green" chemistry. In our work, it was shown that the interaction of 1-adamantanol in the presence of 5 molar % of aluminum triflate in nitromethane medium with such N-nucleophiles as primary carboxylic or sulfonic acid amides, ethylurethane, low-basic aromatic amines and 1,2,3-benzotriazole, provides the desired N-adamantilated products with a good yields. The proposed method of adamantylation has several advantages over those previously described and can be used in the preparation of practically significant intermediates for the synthesis of biologically active adamantyl-containing compounds.