Cleaving Carbon-Carbon Bonds by the Release of Trifluoroacetate to Remodel Molecules and Assemble Fluorinated Structures

Abstract

Cleaving carbon-carbon bonds is a significant synthetic challenge. The release of trifluoroacetate presents a powerful force to break these strong bonds. Herein, a brief review of the role of the release of trifluoroacetate in remodeling organic molecules and synthesizing fluorinated compounds is presented.Trifluoroacetate is used as an activating group to induce the elimination of alcohols and is a common counterion in many synthetic reactions. Additionally, a trifluoroacetyl group can serve as a protecting group. The advantages of a trifluoroacetyl group over an acetyl group are due to the exchange of each of the α-protons with electronegative fluorine atoms. Specifically, these fluorine atoms strongly polarize the adjacent carbonyl group and terminate the tendency of enolate formation from base compared with an acetyl group. Trifluoroacetate has another powerful, yet widely underexplored application, namely it can promote the cleavage of carbon-carbon bonds during its release from an organic molecule. Although breaking carbon-carbon bonds is quite difficult and rarely explored by synthetic chemists, 1-6 studying bond cleavage through trifluoroacetate release presents opportunities to remodel molecular structures as well as generate reactive intermediates. 3 In this review, key advances in the scission of carbon-carbon bonds through the release of trifluoroacetate are presented, along with the applications of the respective reactive intermediates in organic synthesis and medicinal chemistry. The release of trifluoroacetate poses two major pathways to cleave bonds, elimination and fragmentation (Scheme 1). The first part of this review will describe examples of trifluoroacetate release by elimination to generate cationic intermediates to remodel organic structures, and the second part will detail cases of trifluoroacetate release by fragmentation to produce anions to assemble fluorinated molecules.