Novel asymmetric catalysts for the activation of a, beta-unsaturated carbonyl compounds

This thesis embraces two main sections - studies towards the synthesis of a family of indole-based ligands for Lewis acid catalysis and the development of new molecular scaffolds for organocatalytic transformations. Chapter 1 describes some of the recent advances made in metal-free asymmetric catalysis and sets the work involved within this thesis into context. The rational design and synthesis of ligands for Lewis acid catalysis is presented in Chapter 2. The preparation of mono- and bis-(indol-3-yl)ethane-l,2-diols is described along with our initial studies into their use in the asymmetric catalysis of the Diels-Alder reaction. Chapter 3 describes our investigations into the development of the first acyclic system for aminocatalysis via an irninium ion pathway by utilisation of the a-effect, which was shown to be an effective platform for the acceleration of this class of reaction. We went on to apply our new molecular scaffold to a family of chiral aminocatalysts based upon 8-phenylmenthamine, as described in Chapter 4. The catalysts described in Chapter 4 were proposed to affect the diastereoselective discrimination of a,beta-unsaturated carbonyl compounds, owing to the postulated presence of face-face 7t-7t interactions between the double bond of the a,beta-unsaturated moiety in the resulting irninium ion, and an aromatic ring incorporated into the structure of the catalyst. Investigation into the proposed 7C-7C stacking was achieved by the synthesis of catalysts with electron withdrawing and electron donating groups attached to the aromatic ring, followed by utilisation of this family of novel aminocatalysts to promote asymmetric Diels-Alder reactions. A trend was discovered in which the stereoselectivity of the Diels-Alder cycloaddition increased as the electron density of the aromatic ring incorporated into the structure of each catalyst increased the enantiomeric excess of the (2i)-adduct formed between cyclopentadiene and £-cinnamaldehyde improved from 7% using a 4-trifluoromethyl substituent on the aromatic ring to 21% utilising a 4-methoxy group and 39% with a tetrahydronaphthyl-based catalyst. A hypothetical model which readily explains the stereochemical outcome of these aminocatalytic Diels-Alder cycloadditions is proposed