Copper-Catalyzed Protodecarboxylation of Aromatic Carboxylic Acids
COMMUNICATIONS
and dry septum. All solvents were purified by standard pro-
cedures and deoxygenated by three freeze-pump-thaw
cycles prior to use. All reactions were monitored by GC
using n-tetradecane as an internal standard. Response fac-
tors of the products with regard to n-tetradecane were ob-
tained experimentally by analyzing known quantities of the
substances. GC analyses were carried out using an HP-5 ca-
pillary column (phenyl methyl siloxane 30 m3200.25,
100/2.3–30–300/3) and a time program beginning with 2 min
at 608C followed by 308CminÀ1 ramp to 3008C, then 3 min
at this temperature. Column chromatography was performed
using a Combi Flash Companion-Chromatography-System
(Isco-Systems) and RediSep packed columns (12 g). NMR
spectra were obtained on Bruker AMX 400 systems using
CDCl3 as solvent, with proton and carbon resonances at
400 MHz and 100 MHz, respectively. Mass spectral data
were acquired on a GC-MS Saturn 2100 T (Varian).
tal findings in that the reactivity of the benzoic acids
is dominated by short-range inductive effects trans-
mitted via the s-backbone, while long-range meso-
meric effects through the p-system play only a minor
role for their reactivity. They thus help to understand
why both methoxy and nitro groups facilitate the re-
action, especially when in ortho-position.
The geometries of all calculated structures are de-
tailed in the Supporting Information. In the calculated
transition states, both CO2 and [(phen)Cu]+ are
bound through the lone pair of the phenyl anion. No-
tably, carboxylates with electronegative ortho-sub-
stituents (NO2 >F>MeO) decarboxylate via an early
À
transition state, as manifested in a short CO2 phenyl
bond (ca. 1.89 ) and a long Cu phenyl bond (ca.
À
2.03 ) (Figure 2). In contrast, all other derivatives
show a long CO2 phenyl bond (ca. 2.04 ) and a
short Cu phenyl bond (ca. 1.98 ), indicating a late
transition state, as expected for strongly endothermic
reactions.
À
Catalytic Decarboxylation Exemplified in the
Synthesis of Anisole (2b)
À
An oven-dried vessel was charged with 4-methoxybenzoic
acid (1b) (152 mg, 1.00 mmol), Cu2O (7.2 mg, 0.05 mmol),
and
4,7-diphenyl-1,10-phenanthroline
(3c)
(33 mg,
0.10 mmol). After purging the vessel with alternating
vacuum and nitrogen cycles, a degassed solution of NMP
(1.5 mL) and quinoline (0.5 mL) was added via syringe. The
resulting mixture was stirred for 24 h at 1708C, poured into
aqueous HCl (5N, 2 mL), and extracted repeatedly with di-
ethyl ether. The combined organic layers were washed with
brine, dried over MgSO4, filtered, and the solvent was re-
moved by distillation over a Vigreux column affording 2b as
a clear, colorless liquid; yield: 86 mg (80%). Its spectroscop-
ic data matched those reported in literature for anisole,
CAS: [100–66–3]
Figure 2. Molecular structure of the transition state of the
Cu-catalyzed decarboxylation of 2-fluorobenzoic acid.
Acknowledgements
In summary, a general protocol for the Cu-cata-
lyzed decarboxylation of non-activated aromatic car-
boxylic acids has been developed. The reaction path-
way has been investigated with the help of DFT cal-
culations, leading to the conclusion that the reaction
proceeds via a substitution of CO2 against Cu and a
We thank M. Arndt and D. Ohlmann for technical assistance
and gratefully acknowledge the financial support by Saltigo
GmbH.
À
subsequent hydrolytic cleavage of the Cu C bond.
The proposed mechanism correctly predicts the ob-
served reactivity order for the substrates. In current
work, we are exploiting the computational pathway
outlined herein to guide our search for more active
second generation decarboxylation catalysts bearing
other N,N-chelating ligands.
References
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Experimental Section
General Methods
Reactions were performed under a nitrogen atmosphere in
oven-dried glassware containing a teflon-coated stirrer bar
[6] T. Cohen, R. W. Berninger, J. T. Word, J. Org. Chem.
1978, 43, 837–848.
Adv. Synth. Catal. 2007, 349, 2241 – 2246
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