New approaches to metal free asymmetric catalysis

• Main Author: Ruda, Antonio M.
• Published: Cardiff University 2007
• Subjects: 541.39
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.584184

This thesis embraces three main sections: the development of new molecular scaffolds for the organocatalytic Diels-Alder reaction, extension of the studies upon the a-effect and ji-stacking interactions to acyl-ammonium catalysis and development of novel molecular structures for the aminocatalysed Baylis-Hillman reaction. Chapter 1 describes some of the recent advances made in metal-free asymmetric catalysis and sets the work involved within this thesis into context. Chapter 2 describes the investigation of the a-effect and the modulation of face-face ji-jt interactions as a platform for the development of a novel family of catalyst for the aminocatalysed Diels-Alder reaction. After initial investigation on the effect of different counter anions and alternative electron withdrawing groups within achiral catalysts, the a-effect and the face-face ji-jt interactions design concepts were combined within the structure of a series of arenes based on the 8-aryl menthamine scaffold. Experiments performed utilising (L)-cinnamaldehyde and cyclopentadiene provided clear indications that the ji-stacking interaction incorporated within the architecture of the catalyst cloud drive the geometric control of the Diels-Alder adducts, showing a 54% ee (25) utilising the naphthyl group as the aryl unit and a 30% ee (2R) with the 4-TVyV-dimethyl aniline based catalyst. Within Chapter 3 investigations into the a-effect was extended to an acyl-ammonium catalysis by preparation of a series of 4-aminopyridines containing a heteroatom in the ct-position to the N'-1 nitrogen atom. Examination of this series of catalysts in the acylation of 1-cyclohexanol with acetic anhydride revealed that the a-effect has a detrimental effect in terms of reactivity. Moreover, alternative electronic interactions were examined to improve the nucleophilicity of 4aminopyrimidines. Preparation of a novel set of catalysts for the enantioselective acylation of alcohols was also attempted. Chapter 4 describes an investigation into the organocatalysed Baylis-Hillman reaction. Starting from previous work reported in literature, an initial analysis of solvent conditions showed that the presence of small amounts of water in organic solvents significantly improves the reactivity for the reaction catalysed by (5)-proline and imidazole to give up to a 80%. A series of (S)-proline and (5)-histidine derivatives were also investigated as an alternative to the catalytic system (S)-proline/imidazole for the asymmetric Baylis-Hillman reaction, providing an enantiomeric excess of 22% ee (R) with the 2-(2,3,4,5,6-pentafluorobenzamido)-(5)-histidine methyl ester derivative. Minor modification to this class of catalyst also showed that the presence of second amide unit significantly improved the reaction efficiency providing a pleasing 79% yield for the reaction performed in tetrahydrofuran. Finally, the catalytic system of (5)-proline/imidazole was combined into the structure of the dipeptide (S)- proline-(S)-histidine and was also examined as a potential catalyst for the asymmetric Baylis-Hillman reaction.