New methods of specific fluorination.

The application of hypofluorites (fluoroxy-compounds), especially tnfluoromethyl hypofluorite, in the synthesis of fluorinated steroids is described. Hypofluorites are powerful but selective fluorinating agents with unusual electrophilic character. They should find considerable application not only in the synthesis of fluorinated steroids, but for preparation of fluorinated compounds of many different types. INTRODUCTION During the last thirty years organic fluorine compounds have become of considerable economic importance. The initial impetus in this field of Chemistry came during the last War when the 'Manhatten project' demanded the fractionation of the isotopes of uranium hexafluoride. A whole series of perfluoro-organic compounds was synthesized to provide compounds resistant to uranium hexafluonide vapour. In consequence methods of catalytic perfluonination have become well developed and hosts of perfluoro-organic compounds are known in the aliphatic, alicyclic and aromatic series. A more recent development is the realizaton that organic molecules may have their biological properties profoundly changed when an atom of hydrogen is replaced by one of fluorine. For example, the innocent and biologically essential acetic acid is converted into an insidious and powerful poison when one hydrogen of the methyl group is replaced by fluorine as in monofluoro-acetic acid. Not all changes of this kind are similar. Indeed, in medicinal chemistry, important and beneficial drugs have been synthesized by the specific replacement of hydrogen by fluorine. Particularly striking is the situation with corticosteroid drugs. The most active and useful corticosteroids used at present in therapy have the 9-hydrogen and, sometimes, the Ga-hydrogen replaced by fluorine. Typical part structures are shown in formulae (I) and (II). SPECIFIC FLUORINATION OF ORGANIC COMPOUNDS Theoretical considerations suggest that there should be three difference modes of fluorination of organic molecules depending upon whether fluorine atoms, fluorine anions, or fluorine cations are involved. Fluorination by fluorine atoms is the way in which perfluoro-compounds are prepared. In general, fluorine atoms are too reactive to effect the specific fluorination of an organic substrate though by working at low temperature it is possible 285