Difluoromethylene

The iodide ion induced decomposition of trimethyl (trifluoromethyl) tin and of phenyl (trifluoromethyl) mercury represent additional interesting possibilities. The reaction of the tin reagent and iodide ion with (31, X = H) in refluxing glyme for 168 hr gives (32) and the corresponding 6jff,7j0-difluoromethylene adducts in 46% and 7% yields, respectively. ... 

Isocyanides react with fluorine [75 to yield difluoromethylene imines, which tend to dimerize In an inert solvent, imines accept fluorine fioin trifluoromethyl hypofluorite [76, 77] (equation 11)... 

Thiocarbonyl compounds can be converted into difluoromethylene compounds usually under milder conditions than the conesponding carbonyl compounds Ethylene trithiocarbonate reacts smoothly with sulfur tetrafluoride at 110 °C in the absence of catalyst to give 2,2-difluoro-l,3-dithiolane in high yield. Thiuramsul/ides under similar conditions are readily converted into dialkyItrifluo-rometkylamines [11] (equations 13 and 14). 

The transformation of an ester carbonyl group to a difluoromethylene group, which IS usually difficult to perform, can be accomplished by conversion to the thiaesier followed by treatment with diethylaminosulfur trifluoride (DAST). A vanety of ester types react efficiently, although the reaction fails with lactones. Remarkably, trimethylsilylmethyl esters carry through the proeedure with the silyl group intact [13] (equation 17). 

A terminal 1,13 diene with interstitial deka(difluoromethylene) chain is converted to the corresponding diepoxide by repeated reacUon with a very large excess of hypofluorous acid-acetonitrile complex [22](equation 14)... 

Bromination of the homoconjugated 5-(difluoromethylene)-6 6-difluoro-2-norbornene yields different product mixtures under ionic and free-radical conditions 1771 (equation 6)... 

Trifluoromethyl groups are very resistant to hydrolysis, unless they are allylic or benzylic, or vicinal to a carbon linked to hydrogen. In the last case, elimination of hydrogen fluonde leads to the formation of a difluoromethylene group which is key to additional reactions... 

Initial C-perfluoroalkylation of p diketonesoccurs dunng thenUV irradiation in the presence of perfluoroalkyl iodides in liquid ammonia Pluorinated enami-noketones are obtained by subsequent ammonolysis of a difluoromethylene group and removal of the acetyl group [131] C-alkylation of dimethyl malonate takes... 

Much better known are the fluonnatedphosphoranes, which have been widely used m the Wittig reaction for the preparation of fluoroolefms Difluoromethylena tion reactions have been effected by using a variety of conditions Treatment of dibromodifluoromethane with two equivalents of tns(dimethylammo)phosphine m carefully dried tnglyme yields a solution of bromodifluoromethylphosphonium broomide, which very effectively converts ketones to difluoromethylene derivatives A more sensitive reagent is prepared by the addihon of two equivalents of the phosphine to the reaction mixture of fluorohalomethane and a carbonyl compound [39, 40] (equation 40) (Table 14)... 

Dichlorodifluoromethane and triphenylphosphine were used to prepare 3-de-oxy 3-C-difluoromethylene nbose analogues in up to 65% yield [47] (equation 45). 

An older procedure based upon the thermally induced decarboxylation of sodium chlorodifluoroacetate in the presence of triphenylphosphine was used to introduce the difluoromethylene group into a substituted benzo[h]fluoranthene [48] (equation 46)... 

Miller et al. [9] hypothesized rules on the regioselectivity of addition from the study of the base-catalyzed addition of alcohols to chlorotnfluoroethylene. Attack occurs at the vinylic carbon with most fluorines. Thus, isomers of dichloro-hexafl uorobutene react with methanol and phenol to give the corresponding saturated and vinylic ethers The nucleophiles exclusively attack position 3 of 1,1-dichloro-l,2,3,4,4,4-hexafluoro-2-butene and position I of 4,4-dichloro-l,l,2,3,3,4-hexafluoro-1-butene [10]. In I, l-dichloro-2,3,3,4,4,4-hexafluoro-l-butene, attack on position 2 is favored [J/] (equation 5) Terminal fluoroolefms are almost invariably attacked at tbe difluoromethylene group, as illustrated by the reaction of sodium methoxide with perfluoro-1-heptene in methanol [/2J (equation 6). 

The addition of nucleophiles to cyclic fluoroolefins has been reviewed by Park et al. [2 ]. The reaction with alcohols proceeds by addition-elimination to yield the cyclic vinylic ether, as illustrated by tlie reaction of l,2-dichloro-3,3-di-fluorocyclopropene Further reaction results in cyclopropane ring opening at the bond opposite the difluoromethylene carbon to give preferentially the methyl and ortho esters of (Z)-3-chloro-2-fluoroacrylic acid and a small amount of dimethyl malonate [29] (equation 8). 

Anhydrous ammonia adds tofluorooleftns to produce nitriles Tins phenomenon IS used to characterize chemically the terminal difluoromethylene olefin that IS claimed to be m equilibrium with the internal isomer [4] (equation 2) Thus isomerization to the terminally unsaturated isomer prior to attack by ammonia yields the cyanoenamine... 

The addition of primary amines to fluoroolefins under anhydrous conditions yields imines The hexafluoropropene dimer, perfluoro-2-methyl-2-pcntcne, and ten butylamine react to yield a mixture of two compounds m a 9 4 ratio [4] (equation 3) rather than just the major keteiiimme-imine, as previously reported [5] It IS claimed that this result is possible by means of isomerization to the terminally unsaturated difluoromethylene isomer prior to nucleophilic attack Secondary amines add to fluoroolefins under anhydrous conditions to give fluonnated ternary amines m good yields If the fluoroolefin is added to the amine without cooling the reaction mixture, or if an excess of the secondary armne is used, there is a tendency toward dehvdrofluonnation of the ternary amine The products... 

The behavior of strained,/Zuorimiret/ methylenecyelopropanes depends upon the position and level of fluorination [34], l-(Difluoromethylene)cyclopropane is much like tetrafluoroethylene in its preference for [2+2] cycloaddition (equation 37), but Its 2,2-difluoro isomer favors [4+2] cycloadditions (equation 38). Perfluoromethylenecyclopropane is an exceptionally reactive dienophile but does not undergo [2+2] cycloadditions, possibly because of stenc reasons [34, 45] Cycloadditions involving most possible combinations of simple fluoroalkenes and alkenes or alkynes have been tried [85], but kinetic activation enthalpies (A/f j for only the dimerizations of tetrafluoroethylene (22 6-23 5 kcal/mol), chlorotri-fluoroethylene (23 6 kcal/mol), and perfluoropropene (31.6 kcal/mol) and the cycloaddition between chlorotnfluoroethylene and perfluoropropene (25.5 kcal/mol) have been determined accurately [97, 98] Some cycloadditions involving more functionalized alkenes are listed in Table 5 [99. 100, 101, 102, 103]... 

Similarly, partially fluorinated and perfluorinated methylenecyclopropanes [57, 52], cyclopropenes [55, 84, 55], cyclobutenes [75, 56], and bicychc alkenes [57, 55, 59, 90] apparently denve dienophilic reactivity from relief of their ground-state strain during reaction Thus 2,2-difluoromethylenecyclopropane and perfluoromethylenecyclopropane undergo exclusive [244] cycloadditions [57, 52] (equations 72 and 73), whereas (difluoromethylene)cyclopropane undergoes only [24-2] cycloadditions [57]... 

The strength of the carbon-carbon bond adjacent to a difluoromethylene group IS hardly affected by the presence of fluorine on the cyclopropyl ring When heated, 2,2 difluoromethylenecyclopropane undergoes methylene-cyclopropane rearrangement [/2 ] Under kinetic control, 2,2 difluoro 1 methylenecyclopropane and (difluoromethylene)cyclopropane are formed in a 2 1 ratio, although the latter IS slightly more stable [129] (equation 27)... 

Difluorospiro[2 2]pentane rearranges to 2,2-difluoromethylene cyclobu tane [130] (equation 28)... 

NMR signals for difluoromethylene moieties range from -85 to -111 ppm (excluding difluorocyclopropyls), with viunal 7jjp values similar to the primary cases More compbcated sphttmg patterns arise from diastereotopic fluorines when a chiral center IS present in the gemmal difluonde Diastereotopic fluonnes may differ in chemical... 

Base-catalyzed loss of hydrogen fluoride from the initially formed //../V-diethylG-ltrifluoro-methyl)-3//-azepin-2-amine (66) to give iV,ALdiethyl-3-(difluoromethylene)-3//-azepin-2-amine (67) occurs on photolysis of 2-(trifluoromethyl)phenyl azide (65) in diethylamine.10... 

The hydrophilic group numbers of the sodium sulfonate (SOj Na+) is +11.0, of methylene (CH2) groups (and also for the methyl group) -0.475, and of difluoromethylene (CF2) groups (also valid for the trifluoromethyl group)... 

Sugars having a difluoromethylene group were prepared by reaction of an aldehyde group in sugars with difluoromethylene tris(dimethyl-amino)phosphorane some of these were 554- 559. Similarly, (Z)- 560) and f ))-. tw-bromofluoroalkene 561 were prepared from l,2 3,4-di-0-iso-propylidene-a-D-gfl/ac/o-hexodialdo-l,5-pyranose (395) by treatment with Ph3P=CFBr. 

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