Tetraphosphine/Pd catalyzed Suzuki-Miyaura reactions of heterocycles
probably ascribed to the presence of tetraphosphine ligand
L1 reducing the strong coordination of amino group to the
palladium. The results also demonstrate that multidentate ligands
have advantages for the reaction involving aminoheterocycles.
As p-electron excessive heteroaromatics, thiophenes and
furanes are unfavorable for the oxidative addition process in
theory. However, in the presence of 0.1 mol% catalyst the
couplings of 2-bromothiophene and 3-bromofuran with 3-
pyridineboronic acid proceeded to provide the corresponding
biheteroaryls in good yields (Table 3, entries 10 and 11); similar
efficacy was exhibited for the reaction of 3-bromopyridine.
As is well known, due to the relatively slow rate of oxidative
addition, aryl or heteroaryl chloride is not an active partner
for Suzuki cross-coupling. With the [Pd(Z3-C3H5)Cl]2/L1 catalyst
system, moderate yields of biheteroaryls could be provided for
the reactions of 3-pyridineboronic acid with chloroheterocycles
(Table 3, entries 12–16), and no homocoupling products were
detected; it is less efficient in comparison to those successful
catalyst systems based on monophosphines.[27–33] Previous
studies demonstrated that ligands combination of both elec-
tronic and steric properties are of benefit for the Suzuki
reaction of non-activated substrates. Although tetradentate
phosphine could effectively restrain the poisoning of catalyst
when heterocycles are used, lack of an electron-donating group
and sufficient steric pressure in L1 probably lead to the catalyst
system being less efficient for the reactions of chloroheterocycles.
We aim to design new, easily prepared tetraphosphines posses-
sing a fine balance of electronic and steric properties in the hope
that these ligands will display an excellent catalytic performance.
We also described the reactions of 3-thiopheneboronic
acid with heteroaryl halides and the results are illustrated in
Table 4. Polar solvents are often employed to facilitate the
reaction of heterocycles. However, thiopheneboronic acids are
prone to decomposition under this condition, which becomes the
limitation plaguing the reactions involving these substrates.[30]
We were pleased to find that the protodeboronation process
was not observed in our protocol. By use of 0.1–0.2 mol%
catalyst the reactions of bromopyridines, bromopyrimidine,
bromoaminopyridine and bromothiophene with 3-thiophene-
boronic acid proceeded in good to excellent yields (Table 4,
entries 1–5). However, chloroheteroaryls coupling with 3-thio-
pheneboronic acid did not lead to satisfactory yields (Table 4,
entries 6 and 7) and homocoupling products were not detected.
This is presumably due to the relatively slow rate of oxidative
addition to these substrates.
products and stabilize the active palladium species. Unfortu-
nately, this catalyst system is less efficient for chloroheteroaryls,
and only moderate yields are obtained. Further work to improve
the structure of the ligand is in progress.
Experimental
General Procedure of Suzuki Coupling Reactions
All reactions were carried out under argon atmosphere with
the standard Schlenk techniques. Tetraphosphine L1 (8.5 mg,
0.01 mmol) and [Pd(Z3-C3H5)Cl]2 (1.8 mg, 0.005 mmol) were
added to a Schlenk tube equipped with a magnetic bar, and then
degassed DMA (0.5 ml) was added. The mixture was stirred at
120ꢀC for 20 min. 2-Bromothiophene (48 ml, 0.5 mmol), 3-pyridyl-
boronic acid (92 mg, 0.75 mmol) and K2CO3 (138 mg, 1 mmol)
were added to another Schlenk tube with a magnetic bar. The
dissolved mixture of L1/Pd (50 ml, 0.001 mmol) was transferred
to the Schlenk tube of reactants by syringe. Then, n-butanol
(1.5 ml) was added. The reaction mixture was heated at 110ꢀC
for 12 h. At the end of the reaction, the solution was cooled to
room temperature and water (5 ml) was added. The mixture
solution was extracted with ethyl acetate (3 ꢁ 5 ml) and the
organic layer was dried over magnesium sulfate. The dried
solution was filtered and reduced to ~1–2 ml under vacuum, then
purified by silica gel chromatography to give the corresponding
product with an isolated yield.
Acknowledgements
This work was supported by the National Natural Science Foun-
dation of China (No. 21202104)
Supporting information
Supporting information may be found in the online version of
this article: general experimental details, synthesis of ligand and
1
the H NMR and 13C NMR data for all the products.
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