De Roma, Antonella (2008) Ligands derived from natural substances for asymmetric catalysis. [Tesi di dottorato] (Inedito)

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Abstract

The interaction between biological systems and synthetic chiral molecules has a huge impact on contemporary everyday life and applications range from flavors, fragrances, and food additives to agrochemicals and life-saving drugs. The development of efficient methodologies for the synthesis of the individual enantiomers of a chiral target compound is therefore of continuous interest to scientists in both industry and academia. Among various methods for the preparation of enantiopure molecules, the application of asymmetric catalysis is an attractive option. In the last decades considerable progress has been made in the development of metal-catalyzed asymmetric transformations based on enantiopure ligands complexed to a (transition) metal centre. However, the identification of suitable asymmetric catalysts still poses one of the most challenging endeavours of contemporary chemistry. The research described in this thesis aimed to develop a new class of privileged chiral ligands for asymmetric catalysis, by functionalization of natural molecules such as carbohydrates. Sugars were chosen as building blocks since an appropriate derivatization of the hydroxyls present in their skeleton is suited for the achievement of finely tailored ligands. In particular, the first part of the work was addressed towards the synthesis of new ligands derived from glucose, mannose or galactose. Ligands, which are structurally analogous to the privileged Trost ligands, were examined in the Pd-catalysed asymmetric desymmetrization of meso-2-cyclopenten-1,4-diol biscarbamate in traditional conditions. This intramolecular allylic substitution affords the key precursors of mannostatines, and is also a standard test for the assessment of the stereo-orienting properties of new ligands. In order to demonstrate the applicability of the ligands in other catalytic processes, their use was investigated also in the asymmetric Cu-catalyzed 1,4-conjugate addition of organozinc reagents to acyclic enones. High reactivities and good enantioselectivities (ee values up to 98%) were achieved in both processes. The second part of the actitity aimed at combining the high chemical performance of these catalysts with the increasing need of sustainability demanded by the modern industrial chemistry. For this reason “tagged” versions of the ligands were prepared in order to extend their use in the innovative multiphasic homogeneous conditions. It should be remember that the methodology requires heterogenization of the catalyst, through either its anchorage to a solid support or its selective immobilization in a liquid phase immiscible with the products phase. In these conditions, the catalyst is easily recycled at the end of the reaction by simple phase separation. Thus, the desymmetrization of meso-cyclopenten-2-ene-1,4-diol biscarbamate was performed in the ionic liquid and in homogeneous supported catalysis. The promising results achieved in both cases (up to 4 recycles) give more emphasis to the quality of the new sugar-based ligands, and further stimulates investigation on their use in asymmetric catalysis.

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