Chiral amine is an interesting motive, commonly seen in pharmaceuticals and in chiral auxiliaries and ligands. They are often made from imines and N-heteroarenes by hydrogenation or nucleophilic addition. Traditionally metallic Lewis acids, with chiral ligands, have been used to catalyse these reactions. Recently, interest has grown towards metal-free catalytic systems and this thesis will focus on two emerging fields: chiral counter-ion directed catalysis and asymmetric hydrogenations with frustrated Lewis pairs.
In chiral counter-ion directed catalysis, the chiral catalyst is an organic ion that can bind together with a reagent of opposite charge, where the main binding force is electronic interaction of the ion-pair. Common motives are deprotonated phosphates and disulphonamides. They allow close contact between the ion-pair, which is beneficial for high enantioselectivity. They can also act as a proton shuttle, which speeds up the reaction. Usually the catalyst has a chiral pocket, where the charged group is deeply embedded and surrounded by bulky aromatic groups. These bulky groups orient the reagent, so that the nucleophilic addition is blocked from one side. Imines and N-heteroarenes are excellent reagents for chiral anion catalysis, since they can be easily made cationic by protonation or acetylation. All major reaction types of these substrates can be done with acceptable yields and enantioselectivity.
Frustrated Lewis pair consists of a Lewis acidic and basic group together in one molecule or in two separate ones. Classical Lewis reactivity is kinetically blocked by bulky substituents and therefore they can exist together in a solution. The pair has high thermodynamical energy, which can be used to activate small molecules, for example by splitting dihydrogen into hydride and proton. The activated hydrogen can be catalytically transferred to imines and N-heteroarenes to reduce them. Detailed mechanisms for general hydrogen activation and hydrogen transfer are presented, with some insights into structure-activity relationships. If a chiral group is introduced to the frustrated Lewis pair, chiral amines can be obtained. Generally, the activity and enantioselectivity are lower than with organometal catalyst alternatives, but with certain small imines and N-heteroarenes results are the best seen in asymmetric catalytic hydrogenation. The field hasn’t been yet much explored, but these exceptional results should encourage further studies.
