Organic synthesis in water - Investigations of Lewis acid catalysis and chiral hydrophobic auxiliaries in aqueous Michael additions

University dissertation from Organic Chemistry, Lund University

Abstract: Asymmetrisk katalys har under de senaste decennierna utvecklats kraftigt. År 2001 delade Knowles, Noyori och Sharpless Nobelpriset i kemi för sina banbrytande bidrag inom just detta område. Utmaningen idag är att utveckla nya metoder inom asymmetrisk katalys som även tar hänsyn till vår växande miljöpåfrestning. Nästan alla av dagens kirala katalysatorer är utvecklade för syntes i organiska lösningsmedel, vilket innebär en negativ effekt på både miljö och hälsa In recent years, the improvement of new and practical strategies in asymmetric catalysis has been in the forefront of organic chemistry. The challenge for organic chemists in the 21st century is to apply these strategies to Green Chemistry, such as being resource-efficient and to minimize the production of waste. When the interest in water as a solvent was rejuvenated in the 1990's the concept ?Green Chemistry? was first introduced. Water as a nontoxic, cheap and environmentally benign reaction medium has called for the development of new and practical methods of asymmetric catalysis in aqueous media. The Michael addition is one of the most important C-C bond-forming reactions and since the reaction often leads to a stereogenic center, efforts have been devoted to making the reaction enantioselective. The primary intention with the work presented in this thesis, was to investigate the potential of natural ?-amino acids as chiral ligands in asymmetric Yb(OTf)3-catalyzed Michael additions in aqueous media. We have tried to clarify the details of this reaction through kinetic data as well as studies on how yield and selectivity were influenced by variations in metal/ligand ratio, pH, temperature and ?-amino acids. We found large ligand acceleration for the ?-amino acid complexed Yb(OTf)3-catalysts as well as reversed temperature effects on selectivity for almost all ?-amino acids tested. Various chiral hydrophobic auxiliaries were also synthesized and stereoselectivity in aqueous Michael reactions was observed for some of them.