Sunday, September 8, 2019

XtalFluor-E: Selective Fluorination Reagent


XtalFluor-E (diethylamino difluorosulfunium tetrafluoroborate) appears as one of deoxyfluorinating reagents that improve the weakness of DAST. Different from DAST which is liquid reagents, XtalFluor-E is a solid reagent so it's more stable. 

The mechanism of deoxyfluorination with XtalFluor-E is similar to DAST. The reaction also involves the dialkylaminodifluorosulfane intermediate. However, the difference is, when using XtalFluor-E, it release tetrafluoroboric acid and the reaction also fluoride starved so the side reactions often occur such as the formation of ether compound. For example, see the scheme below. 


Therefore, the reaction with XtalFluor-E usually involves additive such as Et3N.3HF (triethylamine trihydrofluoride) as the source of exogenous fluoride (see the table below). However, the order of the addition of Et3N.3HF should be noted. The yield will be better if the addition of this additive is done with the reagent (XtalFluor-E) before the addition of the substrate. If it is done after the addition of substrate and reagent, then the yield will not be improved because the deoxyfluorination has occurred instantaneously already. That's why the addition of Et3N.3HF after that will be less meaning.   


The addition of strong base might be improving the yield as it will work for the deprotonation. The work from previous table shown also explained that the addition of DBU as non-nucleophile strong base improved the yield of the reaction and reducing the side reactions. Although the yield was improved, the reaction rates were slower than when using Et3N.3HF.

All the data and explanation is refered to this reference:
Heureux, A. L., Beaulieu, F., Bennett, C., Bill, D. R., Clayton, S., Mirmehrabi, M., … Couturier, M. (2010). Aminodifluorosulfinium Salts : Selective Fluorination Reagents with Enhanced Thermal Stability and Ease of Handling †,‡, 3401–3411. https://doi.org/10.1021/jo100504x

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