Cheng-Pan Zhang

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.

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.

Copper-catalyzed trifluoromethylation of alkenes with an electrophilic trifluoromethylating reagent

Summary An efficient method for the copper-catalyzed trifluoromethylation of terminal alkenes with an electrophilic trifluoromethylating reagent has been developed. The reactions proceeded smoothly to give trifluoromethylated alkenes in good to excellent yields. The results provided a versatile approach for the construction of Cvinyl–CF3 bonds without using prefunctionalized substrates.

A Metal-Free Diverse Synthesis of Difluoromethylthioethers and Difluorobis(arylthio)methanes from RSX (X = SR, Cl, SO2Ph) and TMSCF2H

Construction of difluoromethylthioethers (2) and difluorobis(arylthio)methanes (3) from RSX (X = SR, Cl, SO2Ph) and TMSCF2H in the absence of transition metals has been explored. The reaction is dramatically influenced by the nature of the base and the molar ratio of the reactants. Reactions between RSX and TMSCF2H in the presence of CsF provided 2 in good yields, whereas the reaction of RSX with TMSCF2H in the presence of t-BuOK afforded 3 in good yields. These protocols allow for convenient and efficient access to both difluoromethylthioethers and difluorobis(arylthio)methanes.

Enantioselective aldol reaction of cyclic ketones with aryl aldehydes catalyzed by a cyclohexanediamine derived salt in the presence of water

Water was found to be a suitable reaction medium for the direct asymmetric aldol reaction of various cyclic ketones with aryl aldehydes catalyzed by a primary-tertiary diamine-Bronsted acid.

Expeditious trifluoromethylthiolation and trifluoromethylselenolation of alkynyl(phenyl)iodoniums by [XCF3]− (X = S, Se) anions

Trifluoromethylthiolation and trifluoromethylselenolation of alkynyl(phenyl)iodonium tosylates by [XCF3]- (X = S, Se) ions was accomplished in 5-10 minutes at room temperature under a N2 atmosphere and provided a variety of alkynyl trifluoromethyl sulfides and selenides in good yields. Compared to the known methods, this approach has several advantages such as short reaction times and metal- and additive-free conditions without needing excess [Me4N][XCF3] reagents. Moreover, the less efficient reactions of (phenylethynyl)benziodoxol(on)e with [Me4N][XCF3] under the standard conditions demonstrate that acyclic alkynyl(phenyl)iodoniums are more powerful alkynyl sources in the conversion. This protocol allows for a fast and convenient access to numerous alkynyl trifluoromethyl sulfides and selenides.

Palladium-catalyzed Mizoroki–Heck-type reactions of [Ph2SRfn][OTf] with alkenes at room temperature

The first Pd-catalyzed Mizoroki-Heck-type reaction of [Ph2SRfn][OTf] with alkenes is described. The reaction of [Ph2SRfn][OTf] (Rfn = CF3, CH2CF3) with alkenes in the presence of 10 mol% Pd[P(t-Bu)3]2 and TsOH at room temperature provided the corresponding phenylation products in good to high yields. The bases that benefit the traditional Mizoroki-Heck reactions severely inhibited the transformation with [Ph2SRfn][OTf], whereas acids significantly improved the reaction. This protocol supplies a new class of cross-coupling partners for Mizoroki-Heck-type reactions and gains important insights into the reactivity of phenylsulfonium salts either with or without fluorine-containing alkyl groups as the promising phenylation reagents in organic synthesis.

Palladium-Catalyzed Arylation of Arylboronic Acids with Yagupolskii–Umemoto Reagents

A Pd-catalyzed Suzuki cross-coupling of arylboronic acids with Yagupolskii-Umemoto reagents was explored. In contrary to trifluoromethylations, the Pd-catalyzed reaction of R-B(OH)2 and [Ar2 SCF3 ](+) [OTf](-) provided the arylation products (R-Ar) in good to high yields. The reaction confirms that the S-Ar bonds of [Ar2 SCF3 ](+) [OTf](-) can be readily cleaved in the presence of Pd complexes. The relatively electron-poor aryl groups of asymmetric [Ar(1) Ar(2) SCF3 ](+) [OTf](-) salts are more favorably transferred compared to the electron-rich ones. This reaction represents the first report of utilization of [Ar2 SCF3 ](+) [OTf](-) as arylation reagents in organic synthesis.

Recent progress on fluorination in aqueous media

Advances in aqueous fluorination during the last few decades are summarized in this review. Fluorinated compounds have dominated a large percentage of agrochemicals and pharmaceuticals and a mass of functional materials. The incorporation of fluorine atoms into organic molecules has become one of the mainstream technologies for their functional modification. Water is very environmentally friendly and has advantageous physicochemical properties. Fluorination reactions in aqueous media are highly sought-after, and have attracted great attention in research areas ranging from medicinal chemistry to materials science. In early times and for a long time, fluorination was thought to be diametrically opposed to water or moisture. However, recent examples have conflicted with this viewpoint. The successful merger of “untamed” fluorine and “mild” water in chemical reactions has set up a new prospect for green chemistry. A considerable amount of remarkable research works have been carried out using water as a (co)solvent and/or a reactant for transformations including electrophilic, radical, or nucleophilic fluorination. We hope that this review will serve as a guide to better understand and to further broaden the field of fluorine chemistry in aqueous conditions.

Sonogashira Reaction Using Arylsulfonium Salts as Cross-Coupling Partners

Triarylsulfonium, alkyl- and fluoroalkyl(diaryl)sulfonium, and aryl(dialkyl)sulfonium triflates are successfully used as a new family of cross-coupling participants in the Sonogashira reaction as aryldiazonium, diaryliodonium, and tetraphenylphosphonium salts. It was found that terminal alkynes reacted mildly with triarylsulfonium or (2,2,2-trifluoroethyl)diphenylsulfonium triflate at room temperature under Pd- and Cu-cocatalysis to give the corresponding arylalkynes in up to >99% yield. This protocol represents the first use of arylsulfonium salts as cross-coupling partners in the Pd/Cu-catalyzed Sonogashira reaction.