C O M M U N I C A T I O N S
Table 2. Pd-Catalyzed Arylation of Various Heteroaromatic
Table 3. Scope of Aryl Bromide
Carboxylic Acids with PhBr
entry
Ar
−Br
isolated yield (%)
1
2
3
4
5
4-MeO-PhBr
4-NO2-PhBr
2-Br-5-Me-thiophene
3-Br-pyridine
PhBrb
77
66
78
85
57
a See Table 2. b Performed under thermal conditions (140 °C, 1 h).
yield (Table 3). Preliminary results show that thermal conditions
can also be employed (entry 5).
Miura7 reported the use of carboxamides as a sacrificial group
in the arylation of thiazoles, however, multiple arylations were
obtained. An important distinction between our work and that
previously reported7,8 is that it highlights the ability to selectively
perform this reaction in the presence of a reactive C-H group in
an intermolecular fashion and sheds light on the mechanism of this
type of reactivity. Furthermore, it allows for the control of the
arylation such that the monoarylated product is always the major
product observed.
In summary, a decarboxylative cross-coupling reaction for
preparing aryl-substituted heteroaromatics has been disclosed.
Starting from stable and commercially available substrates, this
method allows access to structural motifs that are difficult to obtain
by other methods. The complete control of regiochemistry is an
attractive complement to the existing C-H functionalization
method. Efforts are underway to evaluate the scope and limitation
of this reaction and details will be reported in due course.
Acknowledgment. We wish to thank A. B. Charette for valuable
discussions concerning this work and our colleagues at Boehringer
Ingelheim (Canada), Ltd., R&D for their support and useful
suggestions during the preparation of this manuscript.
a Reaction conditions: heterocycle (0.80 mmol, 2.0 equiv), phenyl
bromide (1.0 equiv), Pd[P(t-Bu)3]2 (5 mol %), n-Bu4N+Cl-‚H2O (1.0 equiv),
Cs2CO3 (1.5 equiv), DMF (4 mL), µW, 170 °C, 8 min. b Isolated yields.
c Yield without additive (yield with n-Bu4N+Cl-‚H2O ) 74% (contains 10%
Supporting Information Available: Experimental procedures and
spectroscopic characeterization of the products. This material is
1
of 1-methyl-2-pyrrole-n-butylester by H NMR)).
will generate 3-phenyl-2-furan carboxylic acid III. This product
can in turn re-enter the catalytic cycle and via I (where R ) Ph)
yield 2,3-diphenylfuran, accounting for the lower yields observed
in the unsubstituted cases. Additionally, when 2-phenylfuran was
subjected to the reaction conditions, only 2,5-diphenylfuran was
observed, ruling out 2-phenylfuran as an intermediate for the
formation of 2,3-diphenylfuran under these conditions.
A comparison of this decarboxylative cross-coupling with the
C-H functionalization method was performed to further highlight
its utility (Scheme 3). In contrast to the C-H functionalization,
where a mixture of the two possible products was obtained (10b
and 13b), appropriate selection of either of the heterocyclic acids
(10a and 13a) afforded the corresponding regioisomer.
References
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Scheme 3. Regioselectivitya
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a Conditions: PhBr, DMF, n-Bu4N+X-, Pd(P(t-Bu)3]2, µW, 170 °C, 8
min.
To further evaluate the scope of this reaction, a variety of aryl
bromides were employed and produced the desired products in good
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