Strategies Towards Asymmetric Conjugate Trifluoromethylation of α,β-Unsaturated Ketones and the Asymmetric Conjugate Addition of Boronates to β-Trifluoromethyl α,β-Unsaturated Ketones

Abstract

Currently, there are no reported methods in the literature for the conjugate addition of the trifluoromethyl group to α,β-unsaturated ketones. A bulk of this thesis focused on developing a method to overcome this problem. Strategies included the preparation of binaphthol-modified trifluoromethylboronates, rhodium-catalyzed conjugate addition of trifluoromethyl bearing reagents and the copper-catalyzed conjugate addition of the trifluoromethylborates. When these methods all proved to be unsuccessful, a different approach was taken towards the ultimate goal of obtaining chiral β-CF3 compounds. The development of the asymmetric conjugate additions to β-trifluoromethyl α,β-unsaturated ketones proved to be an efficient method for obtaining optically active β-CF3 compounds. Successful protocols for the addition of alkenyl, alkynyl and aryl groups are on the verge of being optimized based on the groundwork in this thesis. Because so few protocols currently exist for the synthesis of chiral β-CF3 ketones, these methods will provide a valuable toolkit for the synthesis of novel chiral compounds bearing a trifluoromethyl group.