The Synthesis of homochiral ligandsand their application to asymmetric fluorinating reagents

• Main Author: Bailey, David John
• Published: Durham University 1994
• Subjects: 547; Organic chemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262197

This thesis is concerned with the synthesis of homochiral ligands and their application to asymmetric fluorinations. Initial work focused on the synthesis of homochiral pyridine based ligands and the determination of their optical purity. 2-Acetylpyridine was reduced using bakers' yeast in the presence of an enzyme inhibitor to give a homochiral pyridyl alcohol. A double asymmetric reduction of 2,6-diacetylpyridine was also achieved using bakers' yeast and the resulting diol was also found to be homochiral. Derivatives of the above pyridyl alcohols were then reacted with 10% F2/N2 in the presence of a suitable counterion to form N-fluoropyridinium salts. These reagents were then used to fluorinate a range of silyl ketene acetals and metal enolates to assess their ability as asymmetric electrophilic fluorinating reagents. Although the reagents achieved fluorination, they were found to be poor asymmetric fluorinating reagents. A new synthetic route into the pyrrolidine based amine (2S)-(diphenyl)methylpyrrolidine was developed and its use in a number of asymmetric transformations was investigated. Both DAST and Ishikawa's reagent have proved successful in achieving the replacement of alcohol hydroxyl groups by fluorine. Development of a nucleophilic asymmetric fluorinating reagent based on DAST and Ishikawa's reagent was attempted using (2S)-(diphenyl)methylpyrrolidine as the precursor amine. The homochiral derivatives of DAST and Ishikawa's reagent which were developed, only achieved limited success as fluorinating reagents and the fluorinated products were found to be racemic.(2S)-(Diphenyl)methylpyrrolidine was also found to act as a chiral solvating reagent with certain carboxylic acids and alcohols, these showing chemical non-equivalence by NMK Two (2S)-(diphenyl)methylpyrrolidine units were also coupled together by a two and three carbon bridge forming two novel diamines. Initial studies on the ability of these amines to act as asymmetric catalysts in dihydroxylation reactions using osmium tetroxide and asymmetric addition reactions of Grignard reagents to aldehydes are also described.