a-Fluorobenzylphosphonate esters are conveniently made by treating a -hydroxybenzylphosphonate esters with diethylaminosulphur trifluoride. The reaction is not subject to steric impedance and is extended to the a-fluorination of an a-hydroxybentylphosphine oxide. For a-hydroxyallyl and ahydroxycinnamylphosphonates, the replacement of the hydroxy group by fluorine proceeds via an S,2' rearrangement to give the y-fluoroalk-1 -enylphosphonates exclusively. Dehydration rather than substitution occurs in the case of alcohols of secondary alkylphosphonates.Phosphonates have been widely employed as analogues of biological phosphates.' While there is little doubt that they provide a satisfactory steric simulation of the prototype and the desirable stability of the P-C bond under most conditions, in many areas their biological performance falls short of that anticipated on these grounds. We have argued the case for allotting equal priority to polar and to steric features of phosphonates ' and suggested that a satisfactory solution to the problem could be the use of a-halogenoalkylphosphonates. The preference for a-fluorine substitution rather than a-chlorination is dictated by consideration of the relative chemical inertness of alkyl fluorides relative to chlorides and of the smaller Van der Waals radius for fluorine (0.135 nm) than for chlorine (0.180 nm). Although a considerable number of a-fluoroalkylphosphonates is known,, the methods employed in their preparation are often particular for perfluorinated carbon substrates and few lend themselves to broad utility. We have accordingly undertaken the task of developing general methods for the synthesis of a-fluoroalkylphosphonates and describe here a route for the preparation of a-fluorobenzylphosphonate esters and the corresponding phosphonic acids. A preliminary account of this work has been published earlier., Experimental ' H N.m.r. spectra were recorded at 220 MHz on a Perkin-Elmer R34 spectrometer or at 400.13 MHz using a Bruker WH400 instrument and using tetramethylsilane as an internal reference. ,'P N.m.r. spectra were recorded at 40.48 MHz using a Jeol JNM-PS-1 0 0 spectrometer with proton decoupling. Positive chemical shifts are downfield from 85% phosphoric acid as an external reference. 1.r. spectra were recorded on a Perkin-Elmer 157G grating instrument. High resolution mass spectra were run on a Kratos MSSO instrument with a Kratos DS55 data system. pK,' Values were measured by titration using a Radiometer PHM 28, Autoburette ABU12, and Titrator TT11 with a Titrigraph SBR2c and with a Russell CTWL combination electrode. M.p.s were measured on a Kofler hot stage apparatus and are otherwise uncorrected.Standard laboratory reagents were distilled or crystallised as appropriate before use and solvents were dried by regular procedures.Diethyl a-Hydroxy-2,4,6-trimethylbenzylphosphonate (l).-2,4,6-Trimethylbenzaldehyde (5 g, 34 mmol) was mixed with diethyl phosphite (5 g, 36 mmol) and the mixture was heated with stirring at 100 "C for 8 h then allowed to cool over...
a-Hydroxybenzylphosphonate esters are phosphonates undergo fluorination with allylic reefficiently converted into a-fluorobenzylphosphonate arrangement ; the corresponding phosphonic acids are esters by diethylaminosulphur trifluoride while the formed by de-esterification using bromo-or iodocorresponding a-hydroxyallyl-and cc-hydrosycinnamyl-trimethylsilane.
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