Synthesis studies to single stereoisomers of the vicinal trifluoroalkane motif

Abstract

This thesis focuses on the construction of individual isomers of the R-CHF-CHF-CHF-R’ motif. The multi-vicinal fluorine motif is new in organic chemistry and therefore stereoselective methods giving rapid access to these motifs and with flexibility need to be explored. The research in the thesis succeeded in the preparation of (2S,3R,4S)-314 and (2S,3S,4R)-328. In Chapter 1, an overview of the impact of fluorine in organic molecules is given. Recent developments in asymmetric electrophilic and nucleophilic fluorination are described, as well as the preparation of multivicinal fluoroalkane motifs. Aldol reactions of either (R)- or (S)-N-(α-fluoropropyl)-2-oxazolidinones, mediated by TiCl 4 are reported in Chapter 2. Such aldol reactions gave rise to identical α-fluoro-β-hydroxy- aldol products with high diastereoselectivities (95% dr). After removal from the auxiliary α- fluoro-β-hydroxy- products were converted to the corresponding α,β-difluoro products. The synthesis of non symmetric vicinal trifluoro motifs (2S,3R,4S)-314 and (2S,3S,4R)-328 is described in Chapter 3. They were prepared by direct fluorination in three steps of the corresponding (2R,3R,4R)-erythro and (2R,3S,4S)-threo enantio-enriched epoxy-alcohols. The two erythro and threo epoxy-alcohol isomers behave very differently during the first fluorination step and then an attempt to study and rationalise this difference in behaviour is made.