This thesis describes the use of Brønsted acid catalysis to promote 6-exo-trig cyclisations in the synthesis of N-heterocyclic compounds. In Chapter one, a general overview of alkaloid structures is given, together with a number of general ways for their synthesis, with a particular focus on the Bischler-Napieralski and Pictet-Spengler methods. Hydroamination as a synthetic method is then briefly reviewed to set into context the present project to develop and optimize an acid-catalysed hydroamination method as an alternative protocol to the Picted-Spengler reaction. Chapter two describes different synthetic routes towards the construction of 2-vinylphenylethylamines and their subsequent cyclisations into tetrahydroisoquinoline alkaloids via the acid-catalysed hydroamination methodology. Key aspects of the diastereochemical outcome of the reaction are discussed, as well as the spectral features and limitations of the researched chemistry. Chapter three describes application of the acid-catalysed hydroamination in the making of more complex, polycyclic structures. Synthesis of polymethoxylated tetrahydroisoquinolines, benzhydryl derivatives and a relay synthesis of racemic salsolidine is described. An attempt to synthesise racemic alkaloid, crispine, is briefly discussed, as well as synthesis of an aporphine and a berberine skeleton. Chapter four covers the attempt to extend the acid-catalysed hydroamination chemistry to unprotected indoles and trans-annular cyclisations. Future work and areas of chemistry in which the acid-catalysed hydroamination underperformed or failed to deliver the desired results altogether are briefly discussed. Chapter five contains the experimental remarks and characterisation data.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:667894 |
| Date | January 2014 |
| Creators | Rutkowski, Piotr |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/77061/ |
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