Fluorination decalin

Despite the well-known chemical stability of perfluorinated aliphatic compounds, pcr-fluorinated Decalin can be reacted w ith alkane- or arenethiols under very mild conditions yielding octakis(alkylsulfanyl)- or octakis(arylsulfanyl)naphthalenes 2.6 The reaction starts at the tertiary carbon atoms where the C — F bond is the weakest, since perfluorocyclohexane does not react under similar conditions, but perfluorocyclohexene does.6... 

CoF is used for the replacement of hydrogen with fluorine in halocarbons (5) for fluorination of xylylalkanes, used in vapor-phase soldering fluxes (6) formation of dibutyl decalins (7) fluorination of alkynes (8) synthesis of unsaturated or partially fluorinated compounds (9—11) and conversion of aromatic compounds to perfluorocycHc compounds (see Fluorine compounds, organic). CoF rarely causes polymerization of hydrocarbons. CoF is also used for the conversion of metal oxides to higher valency metal fluorides, eg, in the assay of uranium ore (12). It is also used in the manufacture of nitrogen fluoride, NF, from ammonia (13). 

This electrophilic substitution is unique among chemical transformations, in the sense that a reaction takes place on a completely deactivated site difficult to access by other reactions. With fluorine as a reagent, decalins, bicyclohexyls, alkylcycloalkane derivatives 6-8 and many more can be fluorinated at their tertiary position and subsequently dehydrofluorinated.37... 

Two other totally synthetic variants are of interest. Fluvastatin (Lescol) (marketed in 1993) has been shown to lower LDL cholesterol significantly via competitive inhibition of HMG-CoA reductase. Here an indole ring replaces the decalin structure of lovastatin. With the additional phenyl ring it easily supersedes the hydrophobic requirement for the reductase inhibition. The para-fluorine atom undoubtedly enhances potency. Another experimental entry in this effort is RG12561. 

Highly substituted alkyl fluorides, called perfluoroalkanes, are often used as artificial blood substitutes. These perfluoroalkanes have the ability to transport Oj through the bloodstream as blood does. Some even have twice the O2 transport capability and are used to treat gangrenous tissue. The structure of perfluorodecalin is shown below. How many moles of fluorine must be reacted with one mole of decalin to produce perfluorodecalin ... 

Fluorination at unactivated carbon sites. With fluorine gas (diluted with nitrogen) such a reaction in MeCN at the temperature of ice can be quite efficient. Thus, fluorocyclohexane has been obtained in 63% yield. Note that decalin is fluorinated exclusively at an angular position whereas the secondary carbon sites are attacked by 1-chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate). 

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