10.1002/chem.201905040
Chemistry - A European Journal
COMMUNICATION
previously unreported fluorinated derivative 2q (Scheme 2a).[27]
No purification of the arylsilane was required in this sequence. A
similar two-step protocol for the fluorination of dimethyl
naphthalene-2,3-dicarboxylate (1k), but with the first-generation
iridium catalyst, gave the fluoroarene 2k in a yield over two steps
that was comparable to that obtained for the individual steps
combined (Scheme 2b). This sequence therefore represents a
simple strategy for a sequential meta-selective fluorination of aryl
C–H bonds.
and washed with a saturated solution of NH4OH (4 mL). The aqueous layer
was extracted with CH2Cl2 (3 mL), and the combined organic layers were
dried over Na2SO4. The organic layers were filtered through a short pad of
SiO2, the SiO2 was flushed with CH2Cl2, and the resulting solution was
concentrated under reduced pressure. The product was purified by
preparative thin layer chromatography.
Acknowledgements
[a]
3
We thank the NIH (R35GM130387) for financial support of this
work. We thank Ala Bunescu and Caleb Karmel for fruitful
discussions. P. B. thanks the German National Academic
Foundation (Studienstiftung) for support. D. P. S. thanks the
German Academic Exchange Service (DAAD) for support.
(a) fluorination of natural product O-methylmellenine (
)
1) HSiMe(OTMS)2 (1.5 equiv)
[Ir(cod)OMe] 2 (2.5 mol%)
2,4,7-Me3phen (5.0 mol%)
dioxane, 100 °C, 24 h
(71%)[c]
OMe O
OMe O
O
O
2) KHF2 (6.0 equiv)
Cu(OTf)2 (6.0 equiv)
MeCN, 65 °C, 16 h
(37%)[c]
F
Keywords: fluorination • aryl silanes • copper • nucleophilic
O-methylmellenine (3)
2q
fluoride • fluoroarenes
1kb
(b) silylation-fluorination sequence for the fluorination of non-activated arene
1) HSiMe(OTMS)2 (1.5 equiv)
cyclohexene (1.1 equiv)
[Ir(cod)OMe] 2 (1.5 mol%)
2,4,7-Me3phen (3.1 mol%)
THF, 100 °C, 24 h
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CO2Me
CO2Me
F
CO2Me
CO2Me
2) KHF2 (6.0 equiv)
Cu(OTf)2 (6.0 equiv)
MeCN, 65 °C, 16 h
[d]
1k
2k
, 48%
[a]Reaction was performed with 0.1 mmol of 1q. [b] Reaction sequence was
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performed with 0.3 mmol of dimethyl naphthalene-2,3-dicarboxylate. [c] Isolated
[d]
yield in parentheses.
yields determined by 19F NMR spectroscopy with
fluorobenzene as an internal standard.
Scheme 2. Fluorination of C-H bonds by a combination of iridium-catalyzed
arene silylation and fluorination of the arylsilane.
In summary, we have developed an operationally simple and
direct method for the copper-mediated fluorination of arylsilanes
to fluoroarenes with KHF2. This reaction occurs with readily
available reagents under mild conditions. Electron-rich, electron-
deficient and diversely functionalized arylsilanes undergo
fluorination in moderate to good yield. A sequential process allows
the regioselective fluorination of aryl C–H bonds via the arylsilane
with exquisite regioselectivity, which we also showed in the
context of natural product derivatization. Methods for a related
fluorination of heteroaryl silanes will be part of future studies.
Experimental Section
Inside a glovebox filled with N2, a 4 mL vial was charged with anhydrous
KHF2 (46.9 mg, 0.600 mmol, 6.00 equiv), anhydrous MeCN (1.0 mL),
arylsilane (0.1 mmol, 1 equiv), and anhydrous Cu(OTf)2 (217 mg, 0.600
mmol, 6.00 equiv). The vial was sealed with a Teflon-lined cap, and the
suspension was heated at 65 ºC for 16 h. The resulting mixture was
allowed to cool to room temperature. 1-Fluoro-3-nitrobenzene was added
as internal standard, and the reaction was analyzed by 19F NMR
spectroscopy. For volatile products, the identity was confirmed by GC-MS.
The reaction mixture of non-volatile products was diluted with Et2O (2 mL)
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