C O M M U N I C A T I O N S
Table 3. Coupling with Potassium Pyridyltrifluoroboratea
oxalyl chloride, illustrating potential applications for the synthesis of
biologically interesting fluoren-9-ones.8
The efficiency of this reaction protocol encouraged us to test the
coupling of phenyl acetic acids. Notably, our previous approach using
an oxazoline as the auxiliary for the ortho-coupling failed with
substrates containing R-hydrogens.1a Another existing protocol using
O-methyl hydroxamic acids as a directing group, unfortunately, is not
applicable to sp2 C-H activation/C-C coupling.1e We were pleased
to find that the coupling of phenyl acetic acid with PhBF3K using O2
as the oxidant proceeded effectively to give the diarylated product 5a
in 69% yield. Interestingly, the presence of Ag+ oxidant results in a
complete loss of the reactivity. The presence of an R-substituent
provides sufficient steric hindrance to induce the monoselectivity (5b,
5c). Both strongly electron-withdrawing (5d-5g) and electron-donating
(5j) groups are compatible with this reaction. Aryltrifluoroborates
containing either electron-donating or electron-withdrawing groups
were also effective (5h-j)
a Reaction conditions: 1 (0.5 mmol), 6 (0.7 mmol), Pd(OAc)2 (0.05
mmol), BQ (0.25 mmol), K2HPO4 (1 mmol), O2 or air (20 atm), t-BuOH
(2 mL), 110 °C, 36 h.
in only ∼10% yield, pyridyltrifluoroborate bearing 2-substitution
proved to be effective. Surprisingly, the coupling products under-
went a further intramolecular fluoro-displacement by the carboxyl
groups to give the tricyclic lactones in a one-pot process.
In summary, we have developed a versatile protocol for C-H
activation/aryl-aryl coupling using aryltrifluoroborates. This new
protocol substantially expands the scope of reactions involving
benzoic acids and made possible, for the first time, the ortho-C-H
coupling of phenyl acetic acids containing R-hydrogens, and
electron-deficient arenes. We are currently investigating a possible
effect of ArBF3K on C-H activation reactions and improving the
efficiency of this reaction under 1 atm of air.
Table 2. Coupling of Arylacetic Acids with Potassium
Aryltrifluoroboratesa
Acknowledgment. We gratefully acknowledge the financial
support of the National Institutes of Health (NIGMS, 1 R01 GM084019-
01A1) and A. P. Sloan Foundation for a Fellowship (J.-Q.).
Supporting Information Available: Experimental procedure and
characterization of all new compounds. This material is available free
References
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a 5a, 5c, 5e-5j were isolated as their methyl esters formed by
treating with CH2N2. b Treatment of the coupling products with oxalyl
chloride afforded 5k and 5l.
In general, phenyl acetic acids are a class of broadly useful
starting materials for synthetic chemistry. For example, the reduction
of the nitro group in the methyl ester of 5g to the corresponding
amine simultaneously triggers lactamization to give a synthetically
useful lactam. Treating the coupling products with oxalyl chloride
readily gave the cyclized ketone (5k), and the coupling product
from a drug, ibuprofen, was also converted to a tricyclic enoether
5l by treatment with oxalyl chloride in the presence of trace ethanol.
Considering the importance of heterocycles in medicinal chem-
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via this newly developed coupling protocol. While coupling of
benzoic acids with 3-pyridyltrifluoroborate gave the desired products
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