An Energetic Guide for Estimating Trifluoromethyl Cation Donor Abilities of Electrophilic Trifluoromethylating Reagents: Computations of X–CF₃ Bond Heterolytic Dissociation Enthalpies

Abstract

This work established an energetic guide for estimating the trifluoromethyl cation-donating abilities (TC(+)DA) of electrophilic trifluoromethylating reagents through computing X-CF3 bond (X = O, S, Se, Te, and I) heterolytic dissociation enthalpies. TC(+)DA values for a wide range of popular reagents were derived on the basis of density functional calculations (M06-2X). A good correspondence has been identified between the computed TC(+)DA values and the experimentally observed relative trifluoromethylating capabilities of the reagents. Substituent effects hold good linear free energy relationships on the TC(+)DAs of the most widely used reagents including Umemoto reagent, Yagupolskii-Umemoto reagent, and Togni reagents, which allow their trifluoromethylating capabilities to be rationally tuned by substituents and thus extend their synthetic utility. All the information disclosed in this work would contribute to future rational exploration of the electrophilic trifluoromethylation chemistry.

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

“…All of these sulfonium-based reagents possess a similar aromatic core structure. In the process of studying derivatives of 409 , it was found that the reactivity can be further enhanced by the introduction of electron-withdrawing groups; 260 moreover, sulfonate groups have been used to increase the reagents’ solubility in water and thus simplify purification. 267 As shown in Scheme 68b, nucleophiles can be directly engaged in fluoroalkylation reactions in polar solvents and under mild conditions.…”

Enantiospecific Trifluoromethyl‐Radical‐Induced Three‐Component Coupling of Boronic Esters with Furans

“…We began by investigating a range of commercially available trifluoromethylating agents and found that trifluoromethyldibenzothiophenium salt A (Umemoto's reagent) was optimum 11, 12. Thus, reaction of A with the boronate complex generated from furan‐2‐yllithium and cyclohexylboronic ester 1 a gave the desired product 2 a (ca.…”

Computational I(III)—X BDEs for Benziodoxol(on)e‐based Hypervalent Iodine Reagents: Implications for Their Functional Group Transfer Abilities

“…[15] Such substituent effects remarkably differ from our previously reported linear Hammett dependence of the trifluoromethyl cation-donating ability on substituent constants for Togni's reagents 1f. [16] It can be easily rationalized by the insensitivity of neutral free radicals to electronic effects. When two MeO are located at the 4 and 5 positions (1d8), the BDE increases by 3 kcal/mol.…”