Reaction with difluorine

Many aldehydes and ketones have been converted to g m-difluoro compounds with sulfur tetrafluoride (SF4), " including quinones, which give 1,1,4,4-tetra-fluorocyclohexadiene derivatives. With ketones, yields can be raised and the reaction temperature lowered, by the addition of anhydrous HF. Carboxylic acids, acyl chlorides, and amides react with SF4 to give 1,1,1-trifluorides. In these cases the first product is the acyl fluoride, which then undergoes the ge i-difluorination reaction ... 

A rather complex microwave-assisted ring-opening of chiral difluorinated epoxy-cyclooctenones has been studied by Percy and coworkers (Scheme 6.131) [265]. The epoxide resisted conventional hydrolysis, but reacted smoothly in basic aqueous media (ammonia or N-methylimidazole) under microwave irradiation at 100 °C for 10 min to afford unique hemiacetals and hemiaminals in good yields. Other nitrogen nucleophiles, such as sodium azide or imidazole, failed to trigger the reaction. The reaction with sodium hydroxide led to much poorer conversion of the starting material. 

The author next tried to stabilize the PGI2 structure by introducing second fluorine atom to the 7-position. However, it had been unknown to make such a difluorovinyl ether unit in the literature. We studied difluorination and Wittig reaction as key steps in the synthetic route of the target difluoro-PGl2 from the Corey lactone. After searching the difluorination reaction, it was found that fluorination with A/-fluorobenzenesulfonimide in the presence of potassium bis(trimethylsilyl) amide and manganese dibromide effectively provided the desired difluoride (Table 7) [106]. 

Reactions with imines also occur under similar conditions leading to the formation of difluorinated /1-lactams [196,197]. Formally, this reaction corresponds to a [2+ 2]-cycloaddition across an imine there is also an isolated report of a difluoroketene reaction, shown in Eq. (63) [198]. Useful chemistry of a silyl difluoroketene acetal was reported recently Eq. (64) shows the efficient asymmetric reaction between this reactive carbon nucleophile and aldehydes catalysed by chiral Lewis acids [199]. 

This effect cannot be explained by simply considering differences in frontier orbital energies. A useful monofluorinated dienophile has been prepared [364] using metallated difluoroenol carbamate chemistry (Eq. 143) cycloaddition occurred smoothly with a range of dienes, and desulfination could be achieved under mild conditions without loss of the fluorine atom. Wakselman and co-workers [365] synthesised a rare competent difluorinated dienophile. Lewis acid catalysed Diels-Alder reaction with furan afforded an acceptable yield of (unfortunately) unstable cycloadduct which decomposed to a phenolic product via a dehydrofluorination reaction, circumscribing its utility (Eq. 144). 

The Diels-Alder reaction of a difluorinated dienophile with furans produced cycloadducts which could be converted to difluorinated cyclohexane or cyclohexane polyols.181 Heptaleno[l,2-c]furans undergo Diels-Alder cycloaddition with electron-deficient dienophiles (DMAD, DCE) to produce the corresponding... 

Synthesis of carbonyl difluoride from phosgene 13.7.S.1 Reaction with difluorine... 

Scheme 2.203 Example of the synthesis of gem-difluorinated carbohydrate analogs via a Reformatsky reaction with ethyl bromodifluoroacetate [41c].

Difluorination at C4 of compound 70 with concomitant loss of the methyl group at position 1 was observed on reaction with A-fluoro bis[(trifluoromethyl)-sulfonyl]imide in chloroform. The product 4,4-difluoro-5-methyl-2-phenyl-2,4-dihydro-3//-pyrazol-3-one was obtained in 38% yield. A mechanism was proposed (00JFC135). 

Reaction with Imines. Q ,Q -Dilluoroketones were synthesized through a difluorination of n-butyUmine derivatives with NFSi in acetonitrile with moderate selectivity as the result of the formation... 

Ueki H, Chiba T, Yamazaki T, Kitazume T (2005) Highly regio- and stereocontrolled Sn2 reactions of gem-difluorinated vinyloxiranes with monoalkylcopper reagents. Tetrahedron 61 11141-11147... 

Allylborations of aldehydes have included enantioselective reactions with pinacol allylboronates, catalysed by l,l -spirobiindane-7,7 -diol (SPlNOL)-based phosphoric acids, and with chiral fi-(3,3-difluoroallyl)diisopinocampheylborane to form 1,1-difluorinated homoallylic alcohols with 91-97% ee ... 

The fluorination of P-diketones and p-ketoesters with N-/luorobis(trifluo-romethanesulfonyl)imide (Table 3a, B) can be controlled to give either mono-fluorination or difluorination. Monofluorination occurs when the strong acid, bis(trifluoromethanesulfonyl)imide, a reaction product, is removed by addition of water, which prevents further enolization and fluormation of the monofluoro adduct [83] (equation 38)... 

The extent of mono- versus difluorination of etiolates may also be controlled through the use of N-fluorosultam (Table 3a, G). With a base/W-fIiioro com-pound/substrate ratio of 1.2/1.3-1 6/1, the reaction yields inonofluoro products, but with a ratio of 2.4-3.6/2.6-3 6/1, the difluorinated compounds are obtained [68] (equation 42)... 

In fluorine thermochemistry, two key heat values frequently occur. They are the dissociation energy of difluorine, required for evaluation of fluorine bond energies and the heat of formation of hydrogen fluoride, a product in hydrolysis, hydrogenation, fluorine combustion, or neutralization reactions. These values have been difficult to measure and have changed considerably over the years. A recommended set of values has been reported in recent CODATA bulletins (60) which are collected in Table I together with older values and corrections to update them. 

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