Synthesis of CF3-containing cyclopropanes in a formal [2+1] cycloaddition using Sulfonium- and Ammonium-Ylides

This thesis deals with the development of new methods for the synthesis of trifluoroacetylated cyclopropanes in a formal [2+1]-cycloaddition. Due to the altered properties of fluorine containing medicals or agrochemicals many approaches were made to find ways to synthesize such compounds. A major advantage of a hydrogen-fluorine exchange is the fact that the fluorine doesnt change the steric demand very much, but other properties like the acidity/basicity or the lipophilicity get changed. Such property changes are very important in medicinal chemistry. For example, fluorinated compounds with higher lipophilicity are able to pass the blood-brain barrier. These altered properties however make them difficult to be synthesized with conventional methods. The synthesis with fluorine gas or with hydrofluoric acid is very dangerous and needs many special laboratory inventory. Because of these difficulties, methods are needed to synthesize fluorinated compounds in regular labs. The target molecule herein is a fluorine-containing cyclopropane. These are compounds which react very easily because of their high ring strain. The synthesis of highly functionalized cyclopropanes in a stereochemically defined manner is a very important task. The acceptor was made via a Knoevenagel or a Claisen-Schmidt condensation. The used ylides get formed in situ during the cyclopropanation reaction. The precursor for the ylides are different achiral sulfonium and chiral and achiral ammonium salts. The reaction conditions like the used base, the solvent, the base concentration and others were optimized to increase the yield and the diastereoselectivity. The acetophenone-based onium salt reactions gave yields up to 84 % and a diastereoselectivity up to 92 %. With different bases and ylides the selectivity can be directed to a certain diastereomer. The reaction scope was elucidated with the best suited conditions and asymmetric reactions were performed with an ee up to 70 %. The resulting diastereomers, which were formed during the reaction were identified with NMR and X-ray single crystal structure analysis. Additionally, some isomerization tests were made to proof the stability of the compounds and it was shown that the products isomerize in the presence of a base. The ester-based onium salts gave a very good diastereoselectivity and in the most reactions only one diastereomer was formed. Unfortunately, the yield of these reactions were very low at approximately 30 %. The reactions with the amide-based onium salts gave nearly no product formation.eingereicht von Michael Winter, BScUniversität Linz, Masterarbeit, 2018(VLID)258189