Investigations using chiral scandium (III) Lewis acids

Abstract

Lewis acidic chiral scandium(III) catalysts have been developed and tested with a range of bidentate substrates in both Diels-Alder and aza-Michael reactions. Scandium(III) complexes incorporating bipybox, phenbox (a new class oftetradentate chiral ligand) and pybox ligands, have been found to give significant enantioselectivity in reactions involving 3-acyloxazolidinones and 3-formylpyrone- containing substrates. Molecular modelling has been used to understand more about the action of these catalysts and to design new ligands which can lead to higher levels of enantioselectivity in these reactions. For acyloxazolidinone-containing substrates it was found that scandium(III)/pybox catalysts gave the same sense of stereocontrol in both Diels-Alder and aza-Michael reactions. It was observed that the sense of enantiocontrol with a particular class of ligand was determined by the stereochemistry of the R -substituent on the ligand and the degree of this stereocontrol was influenced by its size. These observations have lead to a proposal of how the substrates bind to the chiral scandium(III) catalysts for each ligand type and how the enantioselectivity of the products is derived. The chiral scandium(III) Lewis acid catalysts were also used to promote an endo- selective intramolecular Diels-Alder reaction of a 3-formylpyrone-containing substrate, the key step in a synthesis of solanapyrone D. This natural product was prepared in up to 77 % ee with all four contiguous formed in this final step of the synthesis. The highest levels of enantioselectivity for this reaction were given by scandium(III)-pybox catalysts. A greater understanding of chiral scandium(III) catalysts, particularly the substrate- catalyst interactions, has been gained in this thesis and can hopefully be used in the future to aid further development of asymmetric catalysis with scandium(III). 11.EThOS - Electronic Theses Online ServiceGBUnited Kingdo