Quaternary ammonium salts as alkylating agents in C-H activation chemistry

Abstract

This thesis focuses mainly on Rh(I)-catalyzed C-H alkylation reactions. Transition metal catalyzed direct alkylation reactions of benzylic amines using alkyl halides and olefins were already investigated in our group. Preliminary results showed, that it is possible to use quaternary ammonium salts as alkylating reagents in this reaction. The olefin is generated in-situ by Hofmann elimination. The formed olefin is able to undergo a direct C-H alkylation reaction of benzylic amines at the benzylic carbon atom directed by 3-substituted pyridin-2-yls. Olefins as alkylating agents are often used in organic chemistry, however short chained olefins like ethylene, propylene or butylene are gaseous at room temperature and highly flammable. Overcoming these drawbacks by substituting olefins with quaternary ammonium salts was the goal of this thesis. Quaternary ammonium salts are solid at room temperature, not particular dangerous and cheap. Therefore this compounds are easy to work with in the organic lab. In the progress of this thesis, we managed to find a working protocol exploiting quaternary ammonium salts as alkylating agents. Furthermore, the reaction conditions were optimized allowing us to perform this reaction with longer chained salts up to C8, generating in that case 1-octene in the reaction mixture upon elimination. Furthermore, a scope of different substituted benzylic amines could be successfully alkylated. Moreover we tried our newly developed method with other literature known C-H alkylation reactions using olefins as alkylating agents. Different substrates and catalysts could be successfully alkylated by our method, showing that this reaction has more applications in the field of direct C-H alkylation reactions. Additional studies to gain a deeper understanding of this reaction were conducted. Kinetic studies into the Hofmann elimination step gained insight on the needed conditions to perform an efficient elimination. Also, experiments towards the correct catalytic active species were performed in cooperation with the Institute of Chemical Technologies and Analytics. Giving us further hints towards proposed reaction mechanism of this Rh(I)-catalyzed alkylation reaction.