Di fluoromethylene

Fluoro- and di-fluoromethylene analogues of nucleosides have formed the subject of recent reviews [96,97]. 

The increasing tendency toward thermal extrusion of CF2 with increasing number of fluorine substituents on the cyclopropane ring has been demonstrated in studies of 1,1-difluorocyclo-propane, 1,1,2-trifluorocyclopropane, 1,1.2,2-tetrafluorocyclopropane,19 and perfluorocyclo-propane.20 Studies of the thermolysis of 1,1,2,2-tetrafluorospiropentane 8 21 and 1,1.2,2-tetra-fluoro-3-methylenecyclopropane (25),22 however, demonstrated that the CF2-CF2 bond in a tetrafluorocyclopropane is substantially weakened. In the case of 25, rearrangement to 2-(di-fluoromethylene)-l,l-difluorocyclopropane (26) occurs irreversibly at 150°C at a rate that was calculated to be 7850 times faster than that of the gem-difluoro analog 21. 

Scheme 2.197 Synthesis of a di-fluoromethylene ketone-derivatized I j artemisinine by use of a difluoroenol silyl ether [31].

Tetrafluorothiirane, 6 (n = 1), lacks a sulfur-sulfur bond and is fairly stable when formed, but it is formed in only 1-2% yield in the above reaction. A more useful synthesis of this monomer is the reaction of thiocarbonyl fluoride with hexafluoropropylene epoxide at 175 °C. At this temperature hexafluoropropylene epoxide serves as a source of di-fluoromethylene, which adds to the double bond of thiocarbonyl fluoride to give the thiirane. If close control of conditions is maintained, yields are close to 40% (6). 

Hydrazones are known to be alternative precursors to gem-di-fluoromethylene compounds. Oxidative gg/n-difluorination of hydra-zones has been performed with fluorine gas, in situ prepared IF from I2 and Fj, or in situ generated BrF from A -bromosuccininiide/Py(HF) . In contrast, anodic oxidation of hydrazones in the presence of fluoride ions provides monofluorinated products predominantly along with smaller amounts of ge/ra-difluorinated products (Scheme 52). ... 

Coupling constants (4/f,h) have been observed in a few instances where fluorine is attached to sp2-hybridized carbon, as, for example, in derivatives of 3-deoxy-3-C-(fluoromethylene)-l,2 5,6-di-O-isopropyli-dene-a-D-ribo- and -xylo-furanose, where JF, h-2 and 4/F, h-4 occur254,264 in the range of 0.5-5.5 Hz, and in 5,6-dideoxy-6,6-difluoro-l,2-0-isopropylidene-3-0-methyl-a-D-xylo-hex-5-enofuranose,251 where 4JFete, h-4 = 2.0 Hz and VFtran. h-4 = 1.5 Hz (cis and trans, relative to H-5). 

A stereochemical dependence has been observed for the 5/f,h-i values observed for a number of 3-deoxy-3-C-(fluoromethylene)-l,2 5,6-di-0-isopropylidene-a-D-ribofuranose derivatives n. =... 

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