Job/Unit: O50370
/KAP1
Date: 04-05-15 14:47:12
Pages: 9
Fluorination of 1,3-Dicarbonyl Compounds
10 mL) were added, and the mixture was extracted. The organic
extracts were then dried (MgSO4), filtered and concentrated to
yield a crude material, which was purified by flash column
chromatography.
librium is dependent on both temperature and fluoride ion
concentration. Both IIII species can then react with the enol
form of a 1,3-dicarbonyl compound to form an IIII-func-
tionalized intermediate. This intermediate can then undergo
a reductive elimination process at IIII to release the fluorin-
ated or acetoxylated product and iodobenzene.
General Procedure C (Monofluorination of Unsubstituted Systems):
A
solution containing PhI(OAc)2 (0.322 g, 1.0 mmol) and
Et3N·3HF (1.63 mL, 10 mmol) was prepared in acetonitrile (8 mL)
and stirred at 75 °C for 15 min. The appropriate 1,3-dicarbonyl
compound (1.0 mmol) was added, and the reaction mixture was
then stirred at 75 °C for 16 h. After this period, water (10 mL) and
Conclusions
We have developed a fluorination of 1,3-dicarbonyl com- CH2Cl2 (3ϫ 10 mL) were added, and the mixture was extracted.
The organic extracts were then dried (MgSO4), filtered and concen-
trated to yield a crude material, which was purified by flash column
chromatography.
pounds using easy-to-handle PhI(OAc)2 and Et3N·3HF.
Interesting differences in reactivity compared to more es-
tablished electrophilic fluorinating agents were displayed.
Preliminary mechanistic analysis suggests an equilibrium
between PhI(OAc)2 and PhIF2, which can lead to compet-
ing acetoxylation in certain cases, although this is mini-
mized by performing reactions at elevated temperatures and
with large excesses (ca. 10 equiv.) of Et3N·3HF. This
fluorination process could reduce our reliance on expensive
N–F electrophilic fluorinating agents and on fluorine gas,
which presents many challenges and requires specialist skills
and equipment for its handling.
Supporting Information (see footnote on the first page of this arti-
cle): Full spectroscopic characterization information for all com-
1
pounds and copies of H and 13C NMR spectra.
Acknowledgments
We thank the University of Warwick Institute of Advanced Study
for a Global Research Fellowship (G. P.). The Warwick Research
Development Fund and the Royal Society are gratefully acknowl-
edged for Research Grants. We thank Dr. Andrew Clark and Prof.
Martin Wills (both Warwick) for generous access to chemicals and
equipment.
Experimental Section
General Information: Solvents and commercially available reagents
were purchased from standard chemical suppliers (Fisher, Sigma–
Aldrich, VWR, Fluorochem) and used as received without further
purification or drying. Reactions were performed under dry nitro-
gen gas. Thin layer chromatography (TLC) was performed on
Merck DF-Alufoilien 60F254 0.2 mm precoated plates. Product
spots were visualized by UV light at 254 nm and subsequently de-
veloped using vanillin or potassium permanganate as appropriate.
Flash column chromatography was carried out using silica gel
(Apollo Scientific 60 Å particle size 40–63 micron). Melting points
are uncorrected. IR spectra were recorded with a Bruker Alpha-P
ATR instrument on the neat compound. NMR spectra were re-
corded with a Bruker DPX-300, DPX 400 or AV III-600 instru-
ment. Low-resolution mass spectra were recorded using electro-
spray ionization (ESI) techniques with an Agilent 6130R instru-
ment. High-resolution mass spectra were recorded using electro-
spray ionization (ESI) techniques with a Bruker Maxis instrument.
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Preparation of 2-Fluoro-1,3-dicarbonyl Compounds
General Procedure A (Fluorination of 2-Substituted Systems): A
solution containing PhI(OAc)2 (0.387 g, 1.2 mmol) and Et3N·3HF
(0.82 mL, 5.0 mmol) was prepared in acetonitrile (8 mL) and
stirred at 40 °C for 15 min. The appropriate 1,3-dicarbonyl com-
pound (1.0 mmol) was added, and the reaction mixture was then
stirred at 40 °C for 16 h. After this period, water (10 mL) and
CH2Cl2 (3ϫ 10 mL) were added and the mixture extracted. The
organic extracts were then dried (MgSO4), filtered and concen-
trated to yield a crude material, which was purified by flash column
chromatography.
General Procedure B (Difluorination of Unsubstituted Systems): A
solution containing PhI(OAc)2 (0.966 g, 3.0 mmol) and Et3N·3HF
(2.45 mL, 15 mmol) was prepared in acetonitrile (8 mL) and stirred
at 40 °C for 15 min. The appropriate 1,3-dicarbonyl compound
(1.0 mmol) was added, and the reaction mixture was then stirred
at 40 °C for 16 h. After this period, water (10 mL) and CH2Cl2 (3ϫ
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