Ji-Chang Xiao

Copper-mediated trifluoromethylation of heteroaromatic compounds by trifluoromethyl sulfonium salts.

Trifluoromethylated organic compounds are becoming increasingly important in organic chemistry. Such compounds often behave in a unique manner because of the special inductive and resonance effects caused by fluorine, and the resilience of the trifluoromethyl group to metabolism. Drug candidates and crop protection agents containing trifluoromethyl groups usually possess improved physical and chemical properties. For example, the strategic introduction of a trifluoromethyl group into fluoxetine (an antidepressant) and efavirenz (an antiviral) was critical to their applications in medicinal chemistry.

Chiral N-heterocyclic carbene catalyzed annulation of α,β-unsaturated aldehydes with 1,3-dicarbonyls

Chiral N-heterocyclic carbene catalyzed annulations of ynals and enals with 1,3-dicarbonyls have been described. The two reactions provided direct and efficient methods for enantioselective synthesis of functionalized dihydropyranones. Comparatively, the reactions starting from ynals were atom-economical; furthermore the reactions of enals demonstrated broader substrate compatibility.

Progress in fluoroalkylation of organic compounds via sulfinatodehalogenation initiation system

The sulfinatodehalogenation reaction represents one of the most important methodologies to incorporate fluorine into organic molecules. Using inexpensive sulfur-containing reactants such as Na(2)S(2)O(4) under mild conditions, per- and polyfluoroalkyl halides (R(F)X, X = Br, I, CCl(3)) can be transformed smoothly into the corresponding sulfinate salts. This method is also used for the perfluoroalkylation of alkenes, dienes, alkynes and aromatics. Notably, after 1998, the sulfinatodehalogenation of perfluoroalkyl chlorides (R(F)Cl) has been realized by using dimethylsulfoxide (DMSO) as a solvent instead of CH(3)CN/H(2)O in the Na(2)S(2)O(4)/NaHCO(3) initiation system. Perfluoroalkyl chlorides, ethyl chlorofluoroacetates and chlorodifluoroacetates, and even nonfluorinated compounds, such as ethyl chloro- or dichloroacetates and chloroform, were either converted into the corresponding sulfinate salts or alkylated alkenes, alkynes and aromatics (including porphyrins). The sulfinatodehalogenation reaction has remarkable advantages. With the increasing demands to utilize the unique properties of fluorine and fluorinated functional groups in medicinal, agricultural and material sciences, we believe that there will continue to be useful developments in sulfinatodehalogenation chemistry and it will be applied more widely in the future.

Direct Trifluoromethylthiolation of Unactivated C(sp3)H Using Silver(I) Trifluoromethanethiolate and Potassium Persulfate

A practical and efficient method for the direct trifluoromethylthiolation of unactivated C(sp(3) )H bonds by AgSCF3 /K2 S2 O8 under mild conditions is described. The reaction has a good functional-group tolerance and good selectivity. Initial mechanistic investigations indicate that the reaction may involve a radical process in which K2 S2 O8 plays key roles in both the activation of the C(sp(3) )H bond and the oxidation of AgSCF3 .

Synthesis and decarboxylative Wittig reaction of difluoromethylene phosphobetaine

A key intermediate, difluoromethylene phosphobetaine, in the Wittig reaction of ClCF2CO2Na-Ph3P with aldehydes was synthesized and characterized, which confirmed the reaction mechanism. The decarboxylation of this stable intermediate was a convenient approach for Wittig difluroolefination. Its reactivity could be adjusted by the modification of the substituent on the phosphorus.

Conversion between Difluorocarbene and Difluoromethylene Ylide

The interconversion between difluoromethylene ylide and difluorocarbene is described. The difluoromethylene ylide precursor, Ph3P(+)CF2CO2(-), could be turned into an efficient difluorocarbene reagent, whereas the classical difluorocarbene reagents, HCF2Cl and FSO2CF2CO2TMS, could generate highly reactive difluoromethylene ylide. Thus the Wittig difluoro-olefination and difluorocyclopropanation could be selectively realized by using the same reagent. In addition, the ylides obtained from different carbene sources showed different reactivity in Wittig reactions.

Monofluorovinyl tosylate: a useful building block for the synthesis of terminal vinyl monofluorides via Suzuki-Miyaura coupling.

Monofluorovinyl tosylate was developed as a practical vinyl fluoride building block to couple with a variety of arylboronic acids in the presence of a palladium catalyst. The high stereoselectivity of 2-aryl-1-fluoroethene derivatives was achieved. This approach is also applicable to the synthesis of 2,2-diaryl-1-fluoroethenes in good yields.

Efficient Heck reactions catalyzed by a highly recyclable palladium(II) complex of a pyridyl-functionalized imidazolium-based ionic liquid†

The reactions of 2-(2-pyridyl)imidazole with alkyl iodides at 25 degrees C in the presence of base gave rise to 1-alkyl-2-(2-pyridyl)imidazole. Subsequent neat reactions with alkyl or polyfluoroalkyl halides at 100 degrees C, followed by anion exchange with LiN(SO(2)CF(3))(2), generated the mono-quaternary ionic liquids. All of them have excellent thermal stability and wide liquid range. Most of the salts with asymmetric N-substituents are liquid at room temperature. The effect of N-substituent variation and symmetry on NMR, TGA and DSC is discussed. Reaction of with palladium(II) chloride produced a mononuclear palladium ionic liquid complex, the structure of which was confirmed by single-crystal X-ray diffraction analysis. The Heck cross-coupling reactions using in ionic liquid demonstrated excellent stability and recyclability.

2,2,2-Trifluoroethylation of Styrenes with Concomitant Introduction of a Hydroxyl Group from Molecular Oxygen by Photoredox Catalysis Activated by Visible Light

The visible-light-induced photoredox difunctionalization reactions of styrenes with 1,1,1-trifluoro-2-iodoethane under an oxygen atmosphere in the presence of water give γ-trifluoromethyl alcohols. In this radical reaction, the oxygen atom in the product originates from molecular oxygen, and water is shown to be important to promote the reaction.

Difluorocarbene-Derived Trifluoromethylthiolation and [18F]Trifluoromethylthiolation of Aliphatic Electrophiles

The first trifluoromethylthiolation and [(18)F]trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external (radioactive) fluoride ion is described. This transition-metal-free approach is high yielding, compatible with a variety of functional groups, and operated under mild reaction conditions. The conceptual advantage of this exogenous-fluoride-mediated transformation enables unprecedented syntheses of [(18)F]CF3S-labeled molecules from most commonly used [(18)F]fluoride ions. The rapid radiochemical reaction time (≤1 min) and high functional-group tolerance allow access to a variety of aliphatic [(18)F]CF3S compounds in high yields.