C-F Activation of hydrofluorocarbons (HFCs) mediated by aluminum reagents

In the presence of various aluminum reagents, the difluoromethylene group (CF₂) in selected hydrofluorocarbons (HFCs) undergoes a Friedel-Crafts type reaction with aromatic compounds in satisfactory yields.     

Nucleophilic fluoroalkylation of terminal vinyl triflones with SO2CF3 as a removable activating group

Terminal vinyl triflones served as excellent Michael addition acceptors which readily reacted with difluoromethylene phosphabetaine and di- or mono-fluoroalkyl bromides to afford compounds containing CF₂ or CF groups. This fluoroalkylation is characterized by mild reaction conditions, ready availability of reagents and excellent functional-group tolerance.     

Introducing difluoromethylene sulfonamide group via nucleophilic addition of difluoromethylene anion with aromatic aldehydes

A new fluorine-containing synthon, R¹COCF₂SO₂R² (2, R¹, R²=morpholino, piperidino, etc.), was developed for the introduction of difluoromethylene sulfonamide or difluoromethylene group. Under different conditions, 2 reacted readily with aromatic aldehydes to give the corresponding difluoromethylene-containing alcohols or diols in moderate to good yields in the presence of potassium tert-butoxide. Difluoromethylene sulfonamide group was introduced into organic compounds directly for the first time by this method.     

Preparation,stability and acidity of difluoromethylene bis phosphonic acid

Hydrolysis of difluoromethylene phosphonate esters quantitatively yields difluoromethylene $\text{bis}$ phosphonic acid as a dihydrate. $\text{In vacuo}$ drying leads to either the monohydrate or the anhydrous acid. Titration of either the free acid or its disodium salt and computer fit of the data gives all four pKas. The disodium salt and the free acid are thermally stable, and the disodium salt is extremely stable even to strong base.     

Reaction of Diazo Compounds with Difluorocarbene: An Efficient Approach towards 1,1‐Difluoroolefins

A transition‐metal‐free difluoromethylenation of diazo compounds that proceeds under mild conditions has been developed and is based on the use of TMSCF₂Br as the difluoromethylene source and tetrabutylammonium bromide (TBAB) as the promoter. The chemoselective formal carbene dimerization reaction is achieved owing to the electronic properties and the relative stability of the difluorocarbene intermediate.     

有机分子中引入二氟亚甲基方法的最新进展

本综述从直接氟化法和间接氟化法两个方面就近些年来在有机化合物中引入二氟亚甲基的方法进行了概括。直接氟化法中，主要介绍了利用亲核和亲电两类氟化试剂在分子中导入-CF~2-的一些最新进展；间接氟化法则主要介绍了一些新的含-CF~2-的合成砌块在合成二氟亚甲基化合物中的应用。     

Preparation,stability, reactivity and synthetic utility of a cadmium stabilized complex of difluoromethylene phosphonic acid ester

Diethyl bromodifluoromethyl phosphonate reacts readily with cadmium metal to form a stable cadmium complex. Depending on solvent, this functionalized organocadmium reagent exhibits stability for days to months. It reacts with a variety of electrophiles and serves as a synthetically useful source for the introduction of the difluoromethylene phosphonate group into organic compounds.The synthetic utility of a wide variety of fluoromethylene phosphonium ylides has been a major effort in our laboratory over the past several years [1]. The generation and capture of difluoromethylene ylides ($\text{1}$) as a general route to difluoromethylene olefins has been of especial interest to us [2]. In an effort to increase the nucleophilicity of the ylide, we have attempted to prepare the analogous phosphonate ylide ($\text{2}$). Although we have achieved modest success [3] by $\text{insitu}$ capture of ($\text{2}$) in the reaction of

sodium dialkyl phosphites with diethyl bromodifluoromethylphosphonate ($\text{3}$), attempts to pregenerate ($\text{2}$), either from diethyl difluoromethylphosphonate ($\text{4}$) or ($\text{3}$), have met with little success. ($\text{2}$) appears to have minimal stability even at low temperatures, and scale up processes of synthetic value would seem to be difficult.     

Rh-catalyzed intramolecular sp2 C-H bond difluoromethylenation

A new Rh-catalyzed intramolecular coupling reaction of a CF(2)Br group with a 2-aryl of indole or pyrrole via C-H bond activation is presented. This reaction represents a new way of incorporating difluoromethylene groups into organic compounds. Preliminary mechanistic studies suggest that this reaction might not occur via a conventional free radical pathway.     

The thermal rearrangements of 1,1,2,2,4,4-hexafluorospiropentane and perfluorospiropentane

The title compounds were synthesized $\text{via}$ CF₂: addition to the respective methylenecyclopropanes. The hexafluorospiropentane thermally rearranges to 2,2,4,4-tetrafluoro-1-(difluoromethylene)cyclobutane in competition with CF₂: extrusion, whereas perfluorospiropentane decomposes exclusively by CF₂: extrusion.     

Single C−F Bond Cleavage of Trifluoromethylarenes with an ortho‐Silyl Group

The transformation of a single C−F bond of trifluoromethylarenes bearing a hydrosilyl group at the ortho position was achieved. The activation of the hydrosilyl group with a trityl cation in the presence of nucleophiles allowed for selective C−F bond functionalization, for example, by allylation, carboxylation, or chlorination. Further derivatization of the resulting fluorosilylarenes afforded various aromatic difluoromethylene compounds.     

Diels-Alder cycloaddition of novel buta-1,-3-diene derivatives possessing a (diethoxyphosphinoyl)difluoromethyl unit

A series of new buta-1,3-diene derivatives possessing a (diethoxyphosphinoyl)difluoromethylene unit at the terminal carbon was prepared to examine the reactivity for Diels-Alder cycloaddition with various representative dienophiles.     

Synthesis of Diverse α-Fluoroalkoxyaryl Derivatives and Their Use for the Generation of Fluorinated Macrocycles

Introduction of difluorinated functionality has emerged as a powerful means for conformational design with minimal steric footprint. Synthetic approaches for the preparation of aryl difluoromethylene ether containing novel building blocks were established, enabling the inclusion of the aryl difluoromethylene ether system into macrocyclic scaffolds for the first time.     

Plasma polymerization of trifluoromethyl substituted aromatic compounds

Thin film coatings were prepared by polymerizing trifluoromethyl-substituted aromatic compounds in a glow discharge with low power levels and medium pressures. Smooth, continuous films which are adherent and insoluble in conventional solvents were produced. A significant amount of the fluorine content from the monomer was retained in the polymer. The trifluoromethyl group was not removed by the plasma conditions and appeared in the film as trifluoromethyl and difluoromethylene groups. The films were slightly less wettable than those of the unfluorinated films.     

AIBN-initiated radical addition of gem-difluorinated alkyl iodides to alkynes and the Pd-catalyzed Sonogashira coupling reaction of E-phenyl difluoromethylene vinylic iodides with terminal alkynes

The addition of gem-difluorinated alkyl iodides to alkynes initiated by AIBN neatly gave the corresponding difluoromethylene vinyl iodides among which the stereoselectivity of aromatic acetylenes was high. The further coupling reaction of E-phenyl difluoromethylene vinyl iodides with terminal alkynes in the presence of catalytic palladium afforded the substituted difluorinated enynes.     

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.     

Synthesis of difluorinated β-ketosulfones and novel gem-difluoromethylsulfone-containing heterocycles as fluorinated building blocks

A series of new heterocyclic β-ketosulfides was prepared by the reaction of the corresponding heterocyclic thiols with α-bromoacetophenone and its derivatives. Oxidation of the products using m-CPBA gave the corresponding heterocyclic β-ketosulfones, which, on treatment with Selectfluor™ under anhydrous condition underwent electrophilic fluorination resulting in new heterocycles with difluoromethylene moiety adjacent to the sulfur atom and the carbonyl group. Base-induced cleavage of the five types of the resulting products, with different heterocyclic moieties as model compounds, afforded the difluoromethyl sulfones attached to the corresponding heterocycles. They can be considered as interesting fluorinated building blocks for further elaborations.     

Fluorine Effects on Group Migration via a Rhodium(V) Nitrenoid Intermediate

An unprecedented rhodium(III)‐catalyzed hydroarylation of α,α‐difluoromethylene alkynes with N ‐pivaloxyl aroylamides through sequential C−H activation and aryl migration is detailed herein. A large array of α,α‐difluoromethylene alkynes and N ‐pivaloxyl aryl amides were amenable to this transformation, thus providing a novel synthetic protocol for the construction of difluorinated 2‐alkenyl aniline derivatives in high yields and with excellent regioselectivity. Notably, unique fluorine effects were found to underlie the thus unconventional reaction manifold.     

New preparation of difluoroiodomethylsulfanylbenzenes and their radical addition to unsaturated compounds initiated by sodium dithionite

Difluoroiodomethylsulfanylbenzene (3a) and 1-chloro-4-difluoroiodomethylsulfanylbenzene (3b) are novel and efficient difluoromethylating reagents via the reaction with unsaturated compounds, such as alkenes, ethynylbenzene, pent-4-en-1-ols, and pent-4-enoic acids initiated by Na₂S₂O₄, to afford the corresponding adducts, tetrahydrofuran derivatives, and γ-butyrolactones containing difluoromethylene group in moderate to good yields.     

(Diethylphosphinyl)difluoromethyllithium. — Preparation and synthetic application —

The action of lithium diisopropylamide on diethyl difluoromethylphosphonate gives the title reagent which reacts with various electrophiles to introduce difluoromethylene or difluoromethyl unit.     

Metal-free regioselective construction of 2-aryl-2H-tetrazol-5-yl difluoromethylene phosphonates

Three bench-stable difluoromethylene phosphonate hydrazones were prepared from simple diethyl(difluoromethyl)phosphonate within two steps in good yields. The [3 + 2] cycloaddition reaction of these diazo precursors with aryl diazonium salts has been accomplished under metal-free conditions with exclusive regioselectivity. This transformation provides practical access to a broad panel of 2-aryl-2 H-tetrazol-5-yl difluoromethylene phosphonates, including the corresponding derivatives of amino acid...