B(C6F5)3 Catalysed Functionalisation and Dehydrogenation of Nitrogen-Based Heterocycles

The catalytic transformation of α-amino C-H bonds to provide α-substituted amines have gained much attention due to the potential to deliver biologically active compounds. Alternatives to classic strategies using transition metals have been sought, and the use of B(C₆F₅)₃ has become more common. The ability of B(C₆F₅)₃  to abstract a hydride in the α-N position of amines has been previously reported in the literature and provides iminium ion and borohydride species 2.34. We will use the formation of intermediate 2.34 to our advantage in order to achieve different transformations.

Chapter 2 describes the C-H bond activation of amines via hydride abstraction using B(C₆F₅)₃, trapping the generated iminium with indoles as nucleophiles to yield in the desired 4-(3-indolyl)butylamines, scaffolds present in the structure of biologically active compounds. Some of the proposed synthesis for these butylamines compounds suffer from lengthy and costly reactions. We propose a C3 alkylation followed by a ring opening reaction between a wide range of amines and different nucleophiles to access the functionalised products after an extensive optimisation study.

Chapter 3 describes a new strategy for the direct  ehydrogenation of pyrrolidines into pyrroles, based on the hydride abstraction ability of B(C₆F₅)₃. Pyrroles represent the core structure of important pharmaceutical products in medicine, hence new methods towards their synthesis are constantly being sought. However, most of the methods reported in the literature follow a similar Paal-Knorr reaction type, and the small number of direct dehydrogenation procedures that haven been reported suffer from some disadvantages.

Our proposed method affords a high number of different substituted pyrroles in high yields, by employing a silane alkene as a sacrificial acceptor assisting the direct dehydrogenation reaction.