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Investigation into the use of 1,2-diamines in fused heterocycle synthesis

Noble, A; (2012) Investigation into the use of 1,2-diamines in fused heterocycle synthesis. Doctoral thesis, UCL (University College London). Green open access

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Abstract

The introductory chapter of this thesis gives a brief outline of the literature concerning the importance of 1,2-diamines. This includes their biological significance, their successful application to synthetic chemistry, especially in asymmetric synthesis, and methods available for their preparation. One particular method, the nitro-Mannich reaction, is reviewed in more detail. The synthetic utility of the products of the nitro-Mannich reaction is demonstrated by their application to the synthesis of natural products and pharmaceutical agents. Improvements to the scope of the nitro-Mannich reaction through the development of conjugate addition nitro-Mannich reactions are also discussed, including a brief outline of the methods available for asymmetric conjugate additions to nitroalkenes. The introductory chapter closes with the importance of 1,2-diamine-containing fused heterocycles, especially in pharmacological compounds, and describes some of the methods available for their preparation. The results and discussion chapter gives a detailed account of the work that has been performed towards the development of an expedient synthesis of 1,2-diamine-containing fused heterocycles. The synthesis utilises a highly anti-selective reductive nitro-Mannich reaction to form structurally complex β-nitroamines in high yield. These are subsequently reduced to the corresponding 1,2-diamines, which undergo a palladium catalysed intramolecular N arylation to synthesise an array of fused heterocyclic compounds. This cyclisation reaction can be performed highly selectively to form both 2-aminomethylene indolines and 3-aminotetrahydroquinolines through the use of a trifluoroacetyl protecting group. Details of the optimisation studies for the nitro-Mannich, nitro reduction and intramolecular N-arylation reactions are given. Investigations into the further derivatisation of the heterocyclic products are also presented. Finally, investigations into the development of an alternative synthesis of tetrahydroquinolines utilising an intramolecular nitro-Mannich reaction are discussed. The conclusions drawn from the research have been summarised and future investigations to be carried out discussed, including the application of this new methodology to the synthesis of schizozygine. The experimental section presents detailed preparative methods and analytical data for all novel compounds. Finally, X-ray crystallographic data and a comprehensive list of references are provided in the appendices section.

Type:Thesis (Doctoral)
Title:Investigation into the use of 1,2-diamines in fused heterocycle synthesis
Open access status:An open access version is available from UCL Discovery
Language:English
UCL classification:UCL > School of BEAMS > Faculty of Maths and Physical Sciences > Chemistry

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