I have a situation in which I want to hydrolyze a phosphonic acid halide under basic conditions. In my specific case, the halide is a fluorine substituent. Other halides like chlorine and bromine are known to hydrolyze quite quickly under aqueous conditions. Until now fluorine abstraction was not possible, even under strongly basic conditions. An additional substituent on the phosphorous is an oxido moiety which carries a negative charge. I am wondering about two things: Is there the possibility to increase the leaving capacity of fluorine by electron-donating groups in close proximity (bond to the same atom)? When the oxido moiety is replaced by an alkyl group R- or Alkoxygroup RO-, the molecule loses a negative charge, which might stabilize the fluorine and inhibits the hydrolyzation. What are the underlying principles that might explain the problems of hydrolyzation when an oxido moiety is present? Are there other strategies to make hydrolyzation an energetically more favored process?

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    $\begingroup$ You are trying to get a -ve charged (or at least electron-rich) nucleophile to approach an already -ve charged molecule. Can you put a protecting group on the O- species, maybe silyl? $\endgroup$
    – Waylander
    Apr 19, 2023 at 11:26
  • $\begingroup$ I see that 2 negative charges by two oxido substituents would create repulsion and is therefore energetically disfavoured. Oxiodo can be protonated to form hydroxide OH. Mechanistically I would expect that OH is attached to the molecule when F- leaves and is therefore present for a specific amount of time. Silylprotecting groups are usually cleaved by fluoride, which is a side product of the reaction. But for the next reactions I indeed plan to mask the oxido unit. $\endgroup$
    – raptorlane
    Apr 19, 2023 at 11:54
  • $\begingroup$ If you have an OH group the proton is quite likely to transfer to the incoming nucleophile and inactivate it. $\endgroup$
    – Waylander
    Apr 19, 2023 at 12:33


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