COMMUNICATION
Palladium-catalyzed decarboxylative coupling of aromatic acids with aryl
halides or unactivated arenes using microwave heatingw
Adelina Voutchkova,a Abigail Coplin,a Nicholas E. Leadbeaterb and Robert H. Crabtree*a
Received (in Cambridge, UK) 13th August 2008, Accepted 10th October 2008
First published as an Advance Article on the web 6th November 2008
DOI: 10.1039/b813998a
Microwave heating greatly accelerates Pd-catalyzed decarboxyla-
tive coupling of aromatic acids and aryl iodides, and allows the
coupling of benzoic acids with unactivated arenes.
Scheme 1
Aryl–aryl coupling reactions1–11 generally rely on a stoichio-
metric organometallic reagent, such as a boronic acid, with an
aryl halide as the other coupling partner.1 New, greener
coupling partners, such as carboxylic acids, are being ex-
plored3 to replace the boronic acid.6–8 ArH can also be
coupled via C–H activation,2 to replace the aryl halide. With
Scheme 2
carboxylic acids, regioselectivity is achieved because coupling
occurs at the site of decarboxylation, but the reactions tend to
be slow.4 C–H activation is often limited by the need for a
microwave heating under controlled and optimized conditions
directing group to achieve high selectivity.2 Heck4 and
is superior to conventional heating. Reaction times are
Sonogashira reactions5 involving ArCOOH decarboxylation
reduced from many hours to a few minutes. In the more
challenging case of carboxylic acids and arenes as coupling
partners, the reactions yielded no product under standard
conditions, but under our new conditions, success was
achieved for select cases (Scheme 1).
are known. Coupling reactions between activated carboxylic
acids and aryl bromides and chlorides, reported by Goossen,7,8
use a Pd(II)/Cu(I) catalyst system for activated benzoic acids
such as 2-nitrobenzoic acid. An alternative by Wagner uses
catalytic Pd and a stoichiometric Ag salt to couple carboxylic
acids and aryl iodides9a or diaryliodonium salts.9b Unactivated
benzoic acids pose severe difficulties for current methods.
We now find that the reaction time can be significantly
Even though prior work showed no significant microwave
enhancement of decarboxylative coupling,9 we now find a
microwave protocol for the reaction in Scheme 2.
Initial results in a sealed microwave tube indicated that at
200 1C the coupling product was observed after 2 min, but
heating was continued for a further 3 min to assure comple-
tion. Extension to a total time of 10 min gave no advantage. In
all cases, a second product, ArH generated from ArCOOH,
was also observed (Scheme 2, product 2). Unlike some pre-
vious reports,7 in our case there was no difference in the
reactivity between the free acid and the potassium salt so the
former was used in all subsequent reactions. The addition of
K2CO3, along with the Ag2CO3, had no effect on the yield.
Our procedure needs 1 equiv. of silver oxide or carbonate, not
the excess (3 equiv.) previously reported for such reactions.4,9
Screening of palladium precursors showed palladium acetate
gave the best yields. In contrast, Pd/C affords no coupling
product, so decomposition to metal is not suspected. In the
absence of any added ligand, we find low yields of 1 and 2 in
approximately equal amounts. The effect of a number of
ligands on the reaction was also studied (ESI Table 1w).
N-donor ligands, such as pyridine, inhibited coupling, whereas
t
reduced by using Bu-XPhos {PtBu2(o-C6H4Ar)}12 together
with microwave heating, and with Ag2O or Ag2CO3 as ad-
ditive. Intramolecular coupling between ArCOOH and Ar0H
now also becomes possible.
We first optimized the benzoic acid decarboxylative cou-
pling with aryl halides as partners. Surprisingly, we find that
t
phosphines were moderately active. P(iPr)Ph2 and Bu-XPhos
a Chemistry Department, Yale University, 225 Prospect St
New Haven, CT 06520, USA. E-mail: Robert.crabtree@yale.edu;
Tel: +1 203 432 3925
gave the best yields among the phosphines. As previously
reported,9 AsPh3 was also comparable in activity. Chelating
ligands like bipyridine (bpy) and 1,2-bis(diphenylphosphino)-
ethane (dppe) were significantly less active than their mono-
dentate counterparts. SbPh3 was likewise inactive.
b Department of Chemistry, University of Connecticut, 55 North
Eagleville Road, Storrs, CT 06269-3060, USA.
E-mail: nicholas.leadbeater@uconn.edu; Fax: +1 860 486 2981;
Tel: +1 860 486 5076
w Electronic supplementary information (ESI) available: Experimental
and characterization data. See DOI: 10.1039/b813998a
Among solvents with good microwave absorptivity such as
DMSO, DMF and water, a DMSO–DMF (1 : 9) mixture
ꢀc
This journal is The Royal Society of Chemistry 2008
6312 | Chem. Commun., 2008, 6312–6314