Wan, Hayley (2003) A generic parallel combinatorial strategy to water tolerant asymmetric catalysis. Doctoral thesis, Durham University.
Employing parallel and combinatorial strategies, a new water-tolerant ruthenium based method for the in situ oxidation of a hydroxylamine to the corresponding nitroso compound has been developed. It has been discovered that 0.1 mol % of a ruthenium(II)-salen derived complex is able to catalyse the oxidation reaction of an N-Boc-hydroxylamine to the corresponding 7V-Boc-nitroso compound, which can then be trapped out in a [4+2] cycloaddition reaction with a 1,3-conjugated diene. The reaction is complete within 1 hour at room temperature and produces the corresponding cycloadduct, after work up and purification by column chromatography, in an 81 % yield. These same catalytic conditions have also been applied to cycloaddition reactions of the N-Boc-nitroso dienophile with other cyclic and acyclic 1,3-conjugated dienes. One of the fundamental aims of the project was to discover a catalyst that would not only catalyse the oxidation of the hydroxylamine to the nitroso species but also catalyse the cycloaddition reaction of the nitroso species with the conjugated 1,3-diene. Hence, the asymmetric ruthenium(ll)-salen derived catalyst was prepared and tested in the reaction. Unfortunately, although this catalyst works well for the oxidation step, it did not produce asymmetric induction for the cycloaddition reaction. A catalytic cycle and hypotheses for the lack of enantioselectivity have been proposed. It was also discovered that 15 % e.e. could be obtained when a ruthenium(ll)- DIOP system was used in the oxidation-cycloaddition reaction between N-Boc- hydroxylamine and cyclohexadiene, in the presence of 3 equivalents of TBHP. Unfortunately, only a 14 % yield of the corresponding cycloadduct was obtained. The use of nitrosobenzene and ortho-methoxynitrosobenzene as dienophiles in the nitroso Diels-Alder reaction has also been demonstrated. Attempts were made to also discover a water-tolerant asymmetric catalyst for these cycloaddition reactions. Work has also been earned out to show the applications of the acyl-nitroso Diels-Alder cycloaddition reactions towards the synthesis of spider venoms. A synthetic route towards substituted piperidine spider venoms was proposed but due to time constraints, work could not be completed in this area.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||09 Sep 2011 10:01|