Multifunctional map-based structures in organo- and metal-catalysed reactions

Asymmetric catalysis is essential to meeting increasing demands of chiral molecules and substances for pharmaceutical and material industries. Combination of major catalytic approaches to achieve efficient asymmetric catalysis is of current interest but often limited by the design of compatible and cooperative catalytic systems. MAP-based trifunctional systems, containing phosphine as a Lewis base, amine as a Brønsted base, and an aromatic Brønsted acid group, are proficient in cooperative organocatalytic aza-MBH processes and can potentially also serve as multidentate ligands in metal-catalysed reactions for developing hybrid catalysts in sequential organo- and metal-catalysed processes. The application of a single structure as an organocatalyst and ligand in a complex process may present new opportunities for addressing the compatibility issue of hybrid catalysis. 

In this thesis, we report the design, synthesis, and catalytic investigations of new MAP-based trifunctional catalysts for organo- and metal-based catalysis, in single or cascade reactions. First, a new series of trifunctional organocatalysts with various pyrrole-type Brønsted acids were investigated in the aza-MBH reaction to improve catalytic cooperativity and reaction scope. The main representatives of trifunctional MAP-based systems were then tested as ligands in asymmetric allylic substitution and demonstrated the potential to enantiodivergent catalysis, based on the additional ligand-induced H-bonding interactions. A model trifunctional system possessing a phenolic Brønsted acid was also investigated on its organizational ability to translate chirality in cascade or sequential processes. The findings on the organisational properties of MAP-based trifunctional catalytic systems should lead to new design principles in the development of cascade and hybrid catalysis for efficient asymmetric synthesis.