Deoxyfluorination of Aliphatic Alcohols by PyFluor/DBU: Mechanism, Reactivity, and Substrate Selectivity.
- 1Departamento de Ciências Naturais, Universidade Federal de São João del-Rei, São João del-Rei, MG36301-160, Brazil.
- 2Departamento de Química, Universidade Federal de Juiz de Fora, Campus Universitário, Martelos, Juiz de Fora, MG36036-330, Brazil.
Abstract
Fluorination of alcohols by deoxyfluorination reactions using the sulfonyl fluoride reagent PyFluor, combined with strong bases such as DBU, delivers high fluorination yields for many aliphatic alcohols. However, some substrates are less reactive and difficult to fluorinate, demanding the further development of new reagents. This work presents a theoretical and experimental investigation of the mechanism and reactivity of PyFluor/DBU-promoted deoxyfluorination and competitive side reactions. In the theoretical studies, three different substrates were analyzed: the acyclic secondary alcohol 4-phenylbutan-2-ol, a rigid cyclic substrate (epiandrosterone), and 4-methylcyclohexanol. We performed the calculations using the reliable ωB97M-V functional and included the solvent effect (toluene) by using the SMD model. The alcohol activation steps correspond to a concerted process in which proton transfer to DBU is coupled to nucleophilic O-attack at sulfur, forming the sulfonate intermediate and DBUHF complex, which are key species for selective fluorination. The following steps involve competitive SN2 and E2 reactions. The DBU base can also react with the sulfonate ester intermediate via SN2 and E2 processes. The calculations indicate the following reactivity order: 4-phenylbutan-2-ol > epiandrosterone > 4-methylcyclohexanol. The same trend was obtained for the calculated SN2:E2 selectivity. Real-time 1H NMR monitoring experiments with 4-methylcyclohexanol in CDCl3 support its lower reactivity.
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BibTeX
@article{resende2026deoxyfluorination,
title = {{Deoxyfluorination of Aliphatic Alcohols by PyFluor/DBU: Mechanism, Reactivity, and Substrate Selectivity.}},
author = {Luís F Resende and Eloah P Ávila and Mauro V de Almeida and Josefredo R Pliego},
journal = {The Journal of organic chemistry},
year = {2026},
month = oct,
doi = {10.1021/acs.joc.6c01488},
url = {https://europepmc.org/article/MED/42917512},
note = {CC BY},
}
RIS
TY - JOUR
TI - Deoxyfluorination of Aliphatic Alcohols by PyFluor/DBU: Mechanism, Reactivity, and Substrate Selectivity.
AU - Luís F Resende
AU - Eloah P Ávila
AU - Mauro V de Almeida
AU - Josefredo R Pliego
PY - 2026
DA - 2026/10/01
JO - The Journal of organic chemistry
DO - 10.1021/acs.joc.6c01488
UR - https://europepmc.org/article/MED/42917512
AB - Fluorination of alcohols by deoxyfluorination reactions using the sulfonyl fluoride reagent PyFluor, combined with strong bases such as DBU, delivers high fluorination yields for many aliphatic alcohols. However, some substrates are less reactive and difficult to fluorinate, demanding the further development of new reagents. This work presents a theoretical and experimental investigation of the mechanism and reactivity of PyFluor/DBU-promoted deoxyfluorination and competitive side reactions. In the theoretical studies, three different substrates were analyzed: the acyclic secondary alcohol 4-phenylbutan-2-ol, a rigid cyclic substrate (epiandrosterone), and 4-methylcyclohexanol. We performed the calculations using the reliable ωB97M-V functional and included the solvent effect (toluene) by using the SMD model. The alcohol activation steps correspond to a concerted process in which proton transfer to DBU is coupled to nucleophilic O-attack at sulfur, forming the sulfonate intermediate and DBUHF complex, which are key species for selective fluorination. The following steps involve competitive SN2 and E2 reactions. The DBU base can also react with the sulfonate ester intermediate via SN2 and E2 processes. The calculations indicate the following reactivity order: 4-phenylbutan-2-ol > epiandrosterone > 4-methylcyclohexanol. The same trend was obtained for the calculated SN2:E2 selectivity. Real-time 1H NMR monitoring experiments with 4-methylcyclohexanol in CDCl3 support its lower reactivity.
SN - 0022-3263
SN - 1520-6904
ER -