Synthesis Of A New Hypervalent Iodine-based Trifluoromethylating Reagent And Research On Electrophilic Trifluoromethylation

The introduction of trifluoromethyl(CF3) groups into organic compounds substantially changes their acidity, lipophilicity, chemical and metabolic stability. Trifluoromethyl-containing compounds have been widely used in the field of pesticides, pharmaceuticals and materials, etc.Incorporation of trifluoromethyl groups into organic compounds using electrophilic trifluoromethylating reagent is one of the most important methods. The well known electrophilic trifluoromethylation reagents include Umemoto reagent and Togni reagent. With the advancement of technology and the growing social needs, the development of more effective trifluoromethylating reagents has become an urgent demand. In this paper, synthesis of novel trifluoromethylating reagents, and incorporation of trifluoromethyl groups into organic compounds using electrophilic trifluoromethylating reagent have been studied.In the first part, we synthesized a new kind of hypervalent iodine-based trifluoromethylating reagent bearing a pyridine heterocycle in 15% total yield over five steps. Then, we used this new reagent to study the trifluoromethylation of oxygen-centered nucleophiles. However, after comparing the reactivity with Togni reagent, our novel trifluoromethylation reagent was not very satisfactory.In the second part, a new synthetic method of trifluoromethylated phosphonates was developed via electrophilic trifluoromethylation with Togni reagent. A variety of β-keto phosphonates were converted into the corresponding α-trifluoromethyl-β-keto phosphonates in moderate to good yields. This protocol could also be extended to other fluoroalkylation reactions,such as pentafluoroethylation.