Si-Zhan Liu, J. Li, Cao-Gen Xue et al.
Tetrahedron Letters 65 (2021) 152749
Table 2
Scope of the reaction.a
Scheme 2. Plausible reaction mechanism.
withdrawing group at the same position. Additionally, iodobiphe-
nyl, iodonaphthalene, 2-iodopyridine and 2-iodothiophene were
also amenable to this reaction producing corresponding nitrile
compounds 3v-3za in moderate to excellent yields. It should be
noted that aromatic bromide, chlorinate and phenyl trifluo-
romethanesulfonate were not applicable to this reaction, which is
worth for further investigation. Besides, in order to demonstrate
the potential practicability of this method, a gram-scale reaction
of substrate 1a was carried out to afford 3a in 75% yield.
Based on the above results and related literature reports
[
27,28], a plausible reaction mechanism was proposed (Scheme 2).
Initially, in the presence of DMF, the Cu(II) species could be
reduced to the active Cu(I) species [27], which would form inter-
mediate A through the oxidative addition of aromatic iodide
[
14a,27b,28]. Next, intermediate A underwent an anion exchange
with the cyanide ion, which was generated from substrate 2a
under the promotion of Cu(II) catalyst [24], leading to the interme-
diate B. Finally, the reductive elimination of intermediate B would
generate aromatic nitrile product and the active Cu(I) species for
next cycle.
In summary, we have successfully developed a copper-pro-
moted simple and efficient arylcyanation reaction that can be used
to prepare various substituted arylcyanides with diverse function-
ality. Different from most of the known strategies, no additional
ligand and additives were needed with current method. Further
application of this reaction is ongoing in the same group.
a
Reaction conditions: 1 (0.5 mmol, 1 equiv), 2-(dimethylamino)malononitrile 2a
(
1 mmol, 2.0 equiv), Cu
3 4 2
(PO ) (0.1 mmol, 0.2 equiv), DMF (2 mL), 120 °C in a seal
tube for 24 h.
b
1
g of 1a was used.
Declaration of Competing Interest
iodides possessing different substituents with different electronic
and steric properties, and most of the tested aromatic iodides gave
good to excellent yields. Meanwhile all the substituents on the aro-
matic ring, such as halogen atoms (3g to 3m), acetyl (3q) and nitro
groups (3t), kept intact during the reaction. In particular, the pres-
ence of halogen atom, acetyl, nitro and hydroxyl (3u) group pro-
vided additional sites for subsequent derivatization. Moreover, in
the case of substituted benzene iodide, no clear steric effect of
the substituent was observed. For example, when substrates 1d-
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgments
This work is supported by the National Natural Science Founda-
tion of China (21472077 and 21772071), the Fundamental
Research Funds for the Central Universities (lzujbky-2018-134),
the Science and Technology Program of Gansu Province
1
l with a methyl, chloro or fluoro atom substituent were subjected
to this reaction, they all went through the transformation smoothly
to give corresponding products in excellent yields regardless of the
ortho, meta, or para position of the substituent on arene. Further-
more, the use of substrates 1r and 1s with two methyl groups at
both the ortho positions of the iodo atom also afforded the desired
products 3r and 3s in 96% and 91% yields, respectively. In contrast,
the electronic effect of the substituent was observed. Selected
examples like substrates 1a and 1d with electron donating group
at the para-position could give products 3a and 3d in much higher
yields than that of substrates 1q and 1t with a typical electron
(
20JR10RA608), and Department of Education of Guangdong Pro-
vince (No. 2017KTSCX185, 2017KSYS010, 2016KCXTD005,
019KZDXM035).
2
Appendix A. Supplementary data
3