3800
X.-B. Chen et al. / Tetrahedron Letters 53 (2012) 3798–3801
Table 2 (continued)
Entry
Reactant
Product
Cat. (mol %)
Time (h)
12
Yieldb (%)
Cl
Cl
OH
HN
HN
N
14
15
CHO
CHO
5
5
0
N
N
2n
1n
N
N
N
N
CHO
CHO
4
4
71
76
N
1o
2o
Cl
16
5
CHO
N
N
2p
1p
a
Reaction conditions: 5 mmol of substrates in MeOH (30 mL), 10 mmol of sodium acetate, 5–20 mol % PdCl2, H2 (1 atm), 35 °C.
Isolated yield.
b
Table 1, the increase in the loading amount of PdCl2 led to the in-
did not affect the efficiencies of the optimized catalyst system.
Substrates with electron-rich (Table 2, entries 6–8) or electron-
deficient group on the heteroaromatic ring (Table 2, entry 9) read-
ily reacted under similar conditions to give the corresponding
reduced products in high yields ranging from 76% to 88%. At the
same time, functional groups, such as methyl ester, were tolerated
(Table 2, entry 9).
Meanwhile, other halogen-heteroaromatic aldehydes were
investigated under the standard conditions. In order to achieve
the similar results, quinoline compounds required higher catalyst
loading amount of 10 mol % (Table 2, entries 10–12). Hydrodechlo-
rination of dichloroarenes took place smoothly with this catalyst
system to give the corresponding product in excellent yields (Table
2, entry 12). This result exhibited that the present catalyst system
was effective not only for heteroaromatic chlorides but also for aro-
matic chlorides. On the other hand, substituted thiophene afforded
a moderate yield though the catalyst loading amount was increased
up to 20 mol % and the reaction time became 12 h (Table 2, entry
13). Imidazole-substituted aldehydes were tested as well. The re-
sults showed that N-alkylated imidazole compound could only un-
dergo dehalogenation with the aldehyde group remaining, while
with the starting material of 1n, no product was detected (Table
2, entries 14–16). The electron-rich imidazole rings may form com-
plex with PdCl2 which reduced the activity of the catalyst.
crease of the corresponding products. However, further increase
in the amount of catalyst could not continue to improve the yield
significantly (Table 1, entries 1–3). Therefore, these data suggested
that 5 mol % of catalyst should be the best condition. In order to ex-
plore the mechanism of action, the reaction mixture was monitored
alone with time. During the model reaction, nicotinaldehyde as a
debromination product, was detected first in 30 min. The analytical
sample was prepared and its spectral data were found to agree with
the commercial available one, which was then reduced into pri-
mary alcohol in 4 h. Therefore, the mechanism of this one-pot reac-
tion included the dehalogenation reaction happened first and then
the reduction of aldehyde as a final product.
A variety of bases were then examined in the catalytic system.
Among these bases, sodium acetate and 1,8-diazabicyclo [5.4.0]un-
dec-7-ene (DBU) were the most efficient (Table 1, entries 2 and 4).
Other bases such as Et3N, tetramethylethylenediamine (TMEDA),
K2CO3 and tBuOK showed a little or no activity at all (Table 1, entries
5–8). At the same time, the reaction was sluggish in the absence of base
(Table 1, entry 9). These variations in yields ruled out that the base was
not limited to neutralize the generated hydrogen halide. Due to the
lower cost and the slightly higher yield, sodium acetate was chosen
as the most effective base to further investigate the effect of solvent.
Among the tested solvents, methanol was found to be the best (Table
1, entries 2, 10, and 11).
The generality and the limitations of this methodology were
demonstrated by subjecting a broad sampling of functionalized
substrates to conduct the reactions under the optimized condition
as illustrated in Table 2. It is well known that aromatic chlorides
are much less reactive than that of aromatic bromides and hence,
the dechlorination of aromatic chlorides could not readily be
achieved, especially for the heteroaromatic chlorides. In addition,
the reduction of heteroaromatic aldehydes to its corresponding
primary alcohols often requires harsh reaction conditions. Excit-
edly, with the presence of the optimized catalyst system, both
the reduction of aldehyde group and hydrodehalogenation of ha-
lides (bromo- or chloro-functions) took place concurrently in good
yields. Heteroaromatic chlorides and bromides behaved similarly.
With the substrates bearing aldehyde group and halides (bro-
mo- or chloro-functions) at the meta- or ortho-positions of the het-
erocyclic ring, nearly all the reactions performed well (Table 2,
entries 1–3 and 5) except 6-bromopicolinaldehyde, which its cor-
responding reduced product was not detected (Table 2, entry 4).
We also discovered that the presence of additional substituent
In summary, a mild and efficient simultaneous method was
developed for the dehalogenation and hydrogenation of halogen-
heteroaromatic aldehydes using atmosphere pressure hydrogen.
This method generally worked well for a variety of halogen-hetero-
aromatic aldehydes. The simplicity and the reliability of this meth-
od make it an attractive new tool for organic chemists.tpb 2
Acknowledgments
We are grateful for the financial support by the Shanghai Foun-
dation of Science and Technology (09JC1404200), the national ‘863’
Project of China (2011AA10A207) and the Fundamental Research
Funds for the Central Universities (WY1113007).
Supplementary data
Supplementary data associated with this article can be found, in