Sustainable Reductive Aminations Catalysed by Triaryl Borane Frustrated Lewis Pairs

Wright, Noah and Doulcet, Julien (2024) Sustainable Reductive Aminations Catalysed by Triaryl Borane Frustrated Lewis Pairs. PhD thesis, Lancaster University.

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Abstract

Over the past 18 years, frustrated Lewis pairs (FLPs) have advanced significantly from concept to catalysis, however their broad use, for example in reductive aminations has been hampered by their moisture sensitivity and the lack of efficiency for asymmetric catalysis. The work described in this thesis aimed to expand the scope of FLP catalysed reductive amination reactions using moisture tolerant boranes. For this, two axes of focus were chosen: 1) application of FLP-borane catalysed reductive amination to novel substrates, which offer the opportunity for asymmetric reactions; 2) development of continuous flow conditions suitable for reductive amination reactions using hydrogen (this aim was further encouraged by the collaboration with Autichem Ltd. who produces flow reactors). The initial part of this project, described in chapter two, focused on the synthesis of three known moisture tolerant FLP-boranes. The three boranes were obtained in multigram quantities following adaptation of literature procedures. The moisture tolerant boranes synthesised were used to catalyse reductive aminations (and imine reductions) using silanes and hydrogen in batch (chapter three) and using hydrogen in continuous flow (chapter four). Focusing on novel reductive aminations to produce 2-substituted pyrrolidines. Chapter four focused on the development of a proof-of-concept reductive amination system in continuous flow using hydrogen, and despite issues with metal contamination of the flow equipment used, the work performed confirmed that FLPboranes do catalyse imine reduction in flow. To the best of our knowledge this is the first example of such a reaction performed in flow using hydrogen. Finally, chapter five focused on the synthesis of a novel FLP-borane using an azide-alkyne click route. It was envisaged that upon demonstrating the feasibility of this synthetic route, it could be applied to the synthesis of solid supported boranes. Synthesis of the click-borane proved complex; an impure product, assumed to be the desired borane, was obtained but it could not be further purified and further attempts to synthesise it were unsuccessful. Nonetheless, the catalytic activity of the obtained product was demonstrated, and synthesis of an intermolecular analogue demonstrated that triazoles can be effective Lewis bases for imine reduction using hydrogen.