Application of asymmetric C-H activation and cyclopropanation reactions via rhodium carbenoid transformations towards pharmaceutical agents
France, Jessica Ellen
MetadataShow full item record
Formation of C-C bonds through catalytic intermolecular C-H activation can serve as a surrogate to some of the classic reactions of organic synthesis by providing an alternative disconnection strategy. One such example of this approach is the selective C-H activation α to nitrogen with donor/acceptor substituted rhodium carbenoids which serves as the surrogate to the Mannich reaction. The first chapter of this thesis explores the use of this methodology to build a library of methylphenidate analogs. The goal of the project was to build a series of methylphenidate analogs and determine if a potential medication could be developed for the effective treatment for cocaine addiction. The second chapter focuses on the development of novel methyl aryldiazoacetates that contain various functional groups that can serve as coupling partners. Cyclopropanation and C-H insertion reactions were successfully conducted in a highly diastereo- and enantioselective manner with these new methyl aryldiazoacetates. These diazo compounds are synthetically useful because they allow further functionalization, through coupling reactions, to be carried out with the resulting products. This new methodology was applied toward the synthesis of cyclopropyl tamoxifen analogs.