Stereoselective Nucleophilic Halogenation at CF₃‑Substituted Nonclassical Carbocation

CF3-substituted cyclopropyl carbinol derivatives undergo regioselective and diastereoselective nucleophilic halogenation at the quaternary carbon center to provide acyclic products as a single diastereomer. The selectivity of the substitution is rationalized by the formation of a nonclassical cyclopropylcarbinyl cation intermediate, reacting at the most-substituted carbon center. Tertiary alkyl chlorides, bromides, and fluorides adjacent to a stereogenic C–CF3-motif are diastereomerically pure and can be obtained in few catalytic steps from commercially available alkynes

Trifluoromethyl Sulfoxides from Allylic Alcohols and Electrophilic SCF₃ Donor by [2,3]-Sigmatropic Rearrangement

An electrophilic trifluoromethylthiolation of allylic alcohols produces the corresponding allylic trifluoromethanesulfenates, which spontaneously rearrange into trifluoromethyl sulfoxides via a [2,3]-sigmatropic rearrangement. The reaction is straightforward and proceeds in good to high yields for the preparation of various allylic trifluoromethyl sulfoxides

Regio- and Diastereoselective Cu-Mediated Trifluoromethylation of Functionalized Alkenes

α- and β-substituted <i>N</i>,<i>N</i>-diethylacrylamides undergo copper-mediated direct β-trifluoromethylation. The amide moiety acts as a directing group for the regio- and the stereo-controlled introduction of the trifluoromethyl group. The reaction is carried out under acidic conditions in the presence of Umemoto’s reagent. This method does not require prefunctionalized substrates and delivers excellent stereoselectivity

Synthesis of α-CF₃-Substituted Carbonyl Compounds with Relative and Absolute Stereocontrol Using Electrophilic CF₃-Transfer Reagents

Evans-type chiral lithium imide enolates undergo diastereoselective α-trifluoromethylation with a hypervalent iodine–CF₃ reagent with up to 91% combined isolated yield and 97:3 dr. The resulting isolated diastereopure products can be further transformed into valuable products without racemization

Palladium(II)-Catalyzed Directed Trifluoromethylthiolation of Unactivated C(sp³)–H Bonds

The synthesis of trifluoromethyl­thiolated aliphatic acid derivatives by Pd-catalyzed C­(sp³)–H bond functionalization was developed. Using a bidentate directing group, the direct and selective introduction of a SCF₃ moiety was possible on a range of amides with remarkable selectivity for C­(sp³)-centers with an electrophilic SCF₃ source and pivalic acid as an additive. This work constitutes an example of the unactivated C­(sp³)–SCF₃ bond formation by C–H activation offering a new access to relevant molecules

10-Phenylphenothiazine-Organophotocatalyzed Bromo-Perfluoroalkylation of Unactivated Olefins

In this study, we have developed a smooth metal-free visible-light-induced bromo-perfluoroalkylation of unactivated olefins with the aid of 10-phenylphenothiazine (PTH) as an organic photoredox catalyst. The reaction is 100% atom-economic redox-neutral and proceeds with stoichiometric amounts of olefin and perfluoroalkyl bromide. To show the potential of these unexplored motifs, we carried out various postfunctionalizations taking advantage of the bromine atom, including gram-scale experiments

Decarboxylative Allylation of Trifluoroethyl Sulfones and Approach to Difluoromethyl Compounds

Allyl carbonates undergo palladium-catalyzed decarboxylative allylation of trifluoroethyl phenyl sulfones. The success of the allylation, which is not efficient under typical strong base-mediated conditions, is the result of mild conditions thanks to a progressive delivery of ethoxide. Indeed, ethyl allyl carbonates act as a latent source of ethoxide for generation of the trifluoroethyl carbanion that reacts with the π-allylpalladium complex. The utility of the method is illustrated in a new approach to difluoromethyl compounds