Search

Although transition metal carbenes have found widespread applications and difluorocarbene has served as a versatile intermediate, it is still quite challenging to make use of transition-metal difluorocarbenes in synthetic chemistry due to their unpredictable reactivities. In this Highlight, we review recent developments in the transition-metal-catalyzed or -mediated transfer of difluorocarbene and the reactivies and conversions of transition-metal difluorocarbene complexes. We start with the MCF2 bonding, then provide the progress in the transfer of difluorocarbene, and finally briefly discuss the conversions of MCF2 into other metal complexes. The understanding of the interesting reactivities of MCF2 may help design the catalytic transfer of difluorocarbene for various reactions.

Ag-alloyed Cu2ZnSn(S,Se)4 kesterite semiconductors have been attracting considerable attention recently because doping with Ag can suppress the CuZn related anti-site defects, which is the main factor that limits the efficiency of kesterite solar cells. Although the performance of the thin film and the device is enhanced (for example, better crystallinity, fewer deep level defects and longer lifetime of the minority carrier) by doping a small amount of Ag in the CZTS thin film, the density of the defects remains high, and the band alignment of CdS/CZTS is not fully optimized, and the interface carrier concentration is greatly decreased. These phenomena will limit any further improvement in efficiency. In this work, to further increase the performance of the device, the interface of CdS/CZTS for an Ag-alloyed CZTS thin film solar cell was doped with In or Al. Then the properties of the thin film, interface band structure and device performance were investigated. After doping the interface with In or Al, the concentrations of the n-type and p-type carriers at the CdS/CAZTS heterojunction were boosted, and the interface band alignment was optimized, resulting in over 11% efficiency for an Ag-alloyed CZTS (with Al interface doping) thin film solar cell. Moreover, low-cost Al-doped ZnO (AZO) was used to replace indium tin oxide (ITO) as the front electrode after optimization, and more than 10% efficiency of CAZTS device without In was obtained. This study demonstrates the feasibility of controlling the doping of the interface to improve the interface performance of a heterojunction by using a simple spin coating process, and also provided a suitable experimental basis for future low-cost thin film solar cells.

The fluorination of alkenes with electrophilic N-F type reagents usually occurs through a Markovnikov-type addition, and the anti-Markovnikov-type addition may require the use of a transition metal catalyst or an expensive catalyst. Herein we describe a convenient anti-Markovnikov iodofluorination of alkenes with Selectfluor/

For the dehydroxylation of aldoximes with 4-nitro-1-((trifluoromethyl)sulfonyl)-imidazole (NTSI), slight modifications of reaction conditions resulted in significantly different reaction paths to provide either nitriles or isonitriles. The challenging conversion of aldoximes into isonitriles was achieved under mild conditions.

Described herein is a Rh-catalyzed tunable defluorinative borylation of allylic gem-difluorides to provide allylborylated monofluoroalkenes or homoallylborylated monofluoroalkenes with excellent Z/E selectivities. Completely different reaction paths were observed by slightly changing the reaction conditions. Allylborylated monofluoroalkenes were further converted into dihydroxyl-containing monofluoroalkenes.

Difluoromethylation is a straightforward and widely applied strategy used to incorporate HCF2 into organic molecules. In contrast, cyanation reagents are typically volatile or highly toxic, or they require harsh reaction conditions. Incorporation of both CN and HCF2 into organic molecules, such as alkenes, is a worthwhile but challenging task. A method for photocatalyzed cyanodifluoromethylation of alkenes has been developed, which employs a Ph3 P+ CF2 CO2- /NaNH2 (or NH3 ) reagent system. Ph3 P+ CF2 CO2- functions as both the HCF2 and CN carbon source. A cyanide anion is generated in situ under mild conditions, thereby avoiding the use of toxic cyanation reagents. The photocatalytic method permits cyanodifluoromethylation of a range of alkenes under mild room temperature conditions. The CN group within the products may be further derivatized by standard methods.

Although cyanofluoroalkylation has received increasing attention, a toxic cyanation reagent is usually required. Herein, a Cu-catalyzed difluorocarbene-based cyanodifluoromethylation of alkenes with BrCF2CO2Et/NH4HCO3 under photocatalytic conditions is described. BrCF2CO2Et and NH4HCO3 serve as a carbon source and a nitrogen source of the nitrile group, respectively, avoiding the use of a stoichiometric toxic cyanation reagent. The Cu-complex plays a dual role. It is not only a photocatalyst, but also a coupling catalyst for the formation of a C-CN bond.

Owing to the special effects of the fluorine element, including high electronegativity and small atomic radius, the incorporation of a fluorinated group into organic molecules may modify their physical, chemical, and biological properties. Fluorine-containing compounds have found widespread application in a variety of areas, and thus, the development of efficient reagents and methods for the incorporation of fluorinated groups has become a subject of significant interest.Described in this Account are our recent discoveries in the chemistry of fluorinated ylides/carbenes and related intermediates generated from phosphonium/sulfonium salts. Initially, we obtained the (triphenylphosphonio) difluoroacetate, Ph

As a versatile intermediate, difluorocarbene is an electron-deficient transient species, meaning that its oxidation would be challenging. Herein we show that the oxidation of difluorocarbene could occur smoothly to generate carbonyl fluoride. The oxidation process is confirmed by successful trifluoromethoxylation, 18O-trifluoromethoxylation, the observation of AgOCF3 species, and DFT calculations., Difluorocarbene is a versatile and efficient intermediate for fluorine incorporation. Here, the authors show that difluorocarbene can be oxidized to carbonyl fluoride and this process is confirmed in 18O-trifluoromethoxylation reactions, by observation of AgOCF3 species and theory.

As trifluoromethylthiolation has received increasing attention recently, many CF3S-reagents and trifluoromethylthiolation methods have been developed. Herein we describe trifluoromethylthiolation of alkyl halides by using Ph3P+CF2CO2− as a fluoride and difluorocarbene source. Difluorocarbene is a versatile intermediate, but its side reactions are usually ignored and the by-products would therefore be discarded. In this work, a side reaction of difluorocarbene, the generation of a fluoride anion from difluorocarbene, was developed into a synthetic tool. Although the trifluoromethylthiolation reaction involved multi-sequential steps, the cleavage of C–F bond, the formation of CF2=S bond, F-C(S)F2 bond, and C-SCF3 bond, the conversion proceeded fast and was completed within 10 min.

The reaction of thiocarbonyl fluoride, generated from difluorocarbene, with various amines under mild conditions is described. Secondary amines, primary amines, and o-phenylenediamines are converted to thiocarbamoyl fluorides, isothiocyanates, and difluoromethylthiolated heterocycles, respectively. Thiocarbamoyl fluorides were further transformed into trifluoromethylated amines by using a one-pot process. Thiocarbonyl fluoride is generated in situ and is rapidly fully converted in one pot under mild conditions; therefore, no special safety precautions are needed.

Trifluoromethylthiolation by sulfuration of difluorocarbene with elemental sulfur is described for the first time, which overrides long-standing trifluoromethyl anion-based theory. Mechanistic elucidation reveals an unprecedented chemical process for the formation of thiocarbonyl fluoride and also enables transition-metal-mediated trifluoromethylthiolation and [18 F]trifluoromethylthiolation of α-bromo carbonyl compounds with broad substrate scope and compatibility.

Cu-Promoted difluorocarbene-derived trifluoromethylselenolation of benzyl halides with the Ph3P+CF2CO2−/Se/F− system is described. Three new carbon–heteroatom bonds, a Se–CF2 bond, SeCF2–F bond, and C–SeCF3 bond, were sequentially formed in the reaction. This work represents the first trifluoromethylselenolation protocol involving an external fluoride for the generation of the key intermediate, CF3Se− anion.

The O-difluoromethylation of 1,3-diones with S-difluoromethyl sulfonium salt is described. The sulfonium salt was previously believed to be a direct difluoromethylation reagent, but our mechanistic investigation reveals that the O-difluoromethylation reaction proceeds not only via the direct transfer of the CF2H group, but also via a difluorocarbene process. This work represents the first protocol for mild O-difluoromethylation of acyclic 1,3-diones.

The hydroperfluoroalkylation of electron-deficient olefins with perfluoroalkyl iodides promoted by a zinc/viologen system is described. Interestingly, no iodoperfluoroalkylation product was observed without the presence of a radical H-donor.

The Ph3P/ICH2CH2I system-promoted dehydroxylative substitution of alcohols was achieved to construct C–O, C–N, C–S and C–X (X = Cl, Br, and I) bonds. Compared with the previous approaches such as the Appel reaction and Mitsunobu reaction, this protocol offers some practical advantages such as safe operation and a convenient amination process.

DBU-promoted trifluoromethylation of aryl iodides with difluoromethyltriphenylphosphonium bromide (DFPB) in the presence of copper source is described. In this transformation, DBU not only acts as base to deprotonate the difluoromethyl group in DFPB to generate difluoromethylene phosphonium ylide Ph3P+CF2−, but also converts the difluorocarbene generated from ylide Ph3P+CF2− into trifluoromethyl anion, finally resulting in the trifluoromethylation of aryl iodides. The reactions proceeded smoothly to afford expected products in moderate to good yields.

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.

Difluoromethylation of the activated X-H bond (X = N, O and S) and aliphatic thiols, and gem-difluorocyclopropenation of alkynes with difluorocarbene generated in situ from difluoromethylene phosphobetaine (Ph3P(+)CF2CO2(-)) by decarboxylation occurred smoothly without the presence of any base or other additives.

Difluoroethylsulfonium salt, Ph2S+CH2CF2H OTf−, was developed into a convenient difluoromethylcarbene reagent for the iron-catalyzed cyclopropanation of terminal olefins, giving various difluoromethyl–cyclopropanes with excellent diastereoselectivities and in high yields.

Difluoromethylene phosphobetaine (Ph3P+CF2CO2−, PDFA), a known difluorocarbene reagent, was found to be able to efficiently trifluoromethylate terminal alkynes in the presence of Cu(I) and potassium fluoride. The transformation proceeded smoothly to afford the corresponding trifluoromethylated acetylenes in moderate yields.

We have developed an efficient method to achieve N-gem-difluorocyclopropylation of N-heterocycles with the use of gem-difluorocyclopropyl tosylate as a building block under mild conditions. gem-Difluorocyclopropyl tosylates could be easily prepared on a large scale and exhibit great stability.

The copper-mediated trifluoromethylation of terminal alkynes with S-(trifluoromethyl)diarylsulfonium salt has been carefully investigated. The reactions proceeded smoothly to afford trifluoromethylated acetylenes in moderate to good yields. This approach

Organic phosphonium salts have served as important intermediates in synthetic chemistry. But the use of a substituent on the positive phosphorus as a nucleophile to construct C–C bond remains a significant challenge. Here we report an efficient transition-metal-free protocol for the direct nucleophilic arylation of carbonyls and imines with tetraarylphosphonium salts in the presence of caesium carbonate. The aryl nucleophile generated from phosphonium salt shows low basicity and good nucleophilicity, as evidenced by the successful conversion of enolizable aldehydes and ketones. The reaction is not particularly sensitive to water, shows wide substrate scope, and is compatible with a variety of functional groups including cyano and ester groups. Compared with the arylmetallic reagents that are usually moisture sensitive, the phosphonium salts are shelf-stable and can be easily handled., Carbon based nucleophiles often are synthetically limited by the high basicity/reactivity of the starting materials. Here, the authors show that tetraarylphosphonium salts can be induced to act as C-aryl nucleophiles for the addition to carbonyls and imines.

Boron trihalide-promoted ring-opening reactions of gem-difluorocyclopropyl ketones to give the corresponding β-trifluoromethyl ketones and β-halodifluoromethyl ketones were described. It was found that boron trihalides act as both Lewis acids and nucleophiles and the proximal bond prefers to cleave in this transformation.

(2,2,2-Trifluoroethyl)diphenylsulfonium triflate was found to be an efficient ylide reagent for the Johnson–Corey–Chaykovsky reaction to afford trifluoromethyl epoxides, cyclopropanes and aziridines. Interestingly, excellent but different diastereoselectivity was observed for these transformations. Both trifluoromethyl epoxides and cyclopropanes were obtained with trans-selectivity, whereas aziridines were obtained with cis-selectivity.

An efficient method was developed for the synthesis of pentafluoroiodoethane from chloropentafluoroethane. Sulfinatodechlorination of CF3CF2Cl was carefully investigated. Subsequent iodination can be conducted in one pot without further purification, giving the corresponding CF3CF2I in practically acceptable yield.

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.

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.

The CF3SO3H-promoted ring opening of gem-difluorocyclopropyl ketones prefers to undergo proximal bond cleavage and the subsequent cyclization with nitriles occurred smoothly to give 2-fluoropyrroles.

CF(3)- or -CF(2)-containing tetrahydroquinolines have been asymmetrically synthesized from the reaction of fluorinated N-arylimines with benzyl N-vinylcarbamate in the presence of a chiral phosphoric acid.