Copper-mediated amidation of alkenylzirconocenes with acyl azides: Formation of enamides

Article abstract of DOI:10.1021/ol402212g

Copper-mediated amidation of alkenylzirconocenes generated in situ from alkynes and zirconocenes with acyl azides is accomplished under mild conditions. The reaction can be used to prepare various enamides.

Full text of DOI:10.1021/ol402212g

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
Copper-Mediated Amidation of
Alkenylzirconocenes with Acyl Azides:
Formation of Enamides
000–000
†
Hailan Liu, Yiqing Zhou, Xiaoyu Yan, Chao Chen, Qingbin Liu,* and
,‡
†
†
†
,‡
,†
Chanjuan Xi*
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of
Education), Department of Chemistry, Tsinghua University, Beijing 100084, China, and
Institute of Chemistry and Chemical Engineering, Hebei Normal University,
Shijiazhuang 050091, China
cjxi@tsinghua.edu.cn
Received August 5, 2013
ABSTRACT
Copper-mediated amidation of alkenylzirconocenes generated in situ from alkynes and zirconocenes with acyl azides is accomplished under mild
conditions. The reaction can be used to prepare various enamides.
Enamides contain an electron-withdrawing acyl group
on the nitrogen atom, and they display an exception-
ally fine balance of stability and reactivity of nitrogen-
substituted alkenes. Therefore, the enamides provide var-
ious insertions into organic molecules as nitrogen-based
functional compounds and are widely useful in organic
However, the synthetic method involves rather harsh
reaction conditions such as high temperature and/or the
use of strong acids and bases. In recent years, metal-
promoted olefinic CÀN bond formation reactions pro-
vided a powerful and convenient approach to the nitrogen-
4À7
substituted alkenes.
amidation of alkenyl halides with amides provided a
Among them, Pd- or Cu-catalyzed
1
,2
synthesis. The traditional synthetic route to enamides
3
is the thermal decomposition of alkylidenebisamides.
4,5
straightforward method for the formation of enamides.
Meanwhile, copper-promoted amidation of alkenylmetal-
8
†
Tsinghua University.
loids with amides has been also received attention.
‡
Hebei Normal University.
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(
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(
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4110.
amides, see: (a) Xu, J.; Fu, Y.; Xiao, B.; Gong, T.; Guo, Q. Tetrahedron
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2
004, 6, 1809. (d) Jiang, L.; Job, G. E.; Klapars, A.; Buchwald, S. L. Org.
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(
with amides, see: (a) Lu, H.; Yuan, X.; Zhu, S.; Sun, C.; Li, C. J. Org.
Chem. 2008, 73, 8665. (b) Cesati, R. R., III; Dwyer, G.; Jones, R. C.;
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(
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1
0.1021/ol402212g r XXXX American Chemical Society

In addition to the use of amides in amidation reactions,
other N-atom reagents have been rarely reported in the
reaction. Acyl azides are readily accessible and have
participated in a wide range of reactions that constructed
Scheme 2. Amidation of 1a with 2a
9
new carbonÀnitrogen bonds. Moreover, molecular nitro-
gen is released as a byproduct from reactions that is also
very attractive from an environmental perspective. How-
ever, acyl azides as nitrenoid precursors in the amidation
reactions have been far less attention. Our group has
succeeded in the copper-mediated aminations and imina-
tions of alkenylzirconocenes to obtain a wide range of
1
0
11
enamines and enimines, respectively. As part of our
1
ongoing project on alkenylzirconocene chemistry,
2À14
wide scope of various substituents as alkyl, aryl, allyl,
and TMS. The representative results are summarized in
Table 1. In all cases, one product was solely observed. To
confirm their molecular structures, single crystals of the
representative 3da were obtained by the recrystallization in
n-hexane. Its structure revealedthe cis-fashion of its phenyl
and methyl groups (see the Supporting Information),
which was consistent with its substance of the alkenylzir-
conocene 1d, maintaining the configuration of the double
bond during the amidation reaction. Therefore, such a
reaction would be potentially used for a highly substituted
enamides.
Scheme 1. Cu-Mediated Amidation of Alkenylzirconocenes
with Acyl Azides
we envisioned that use of acyl azides as nitrenoid precur-
sors could be applied to the amidation reaction, which
would provide a useful method for the synthesis of enam-
ides. Herein, we describe a copper-mediated amidation of
alkenylzirconocenes withacyl azides toafford a wide range
of enamides under mild conditions (Scheme 1).
To establish the full scope of the amidation reaction, we
further explored a range of acyl azide substrates (Figure 1)
with the alkenylzirconocenes. Aryl acyl azides 2b, 2c, and
2
d derived from benzoyl chloride, p-anisoyl chloride, and
16
p-chlorobenzoyl chloride were also used in the reaction
to give the corresponding enamides (Scheme 3, 3ab, 3cc,
1
5
As an example, alkenylzirconocene 1a, which was
generated by ethanolysis of the corresponding diethylzir-
conacyclopentene prepared from 3-hexyne and Cp ZrEt
3jc, 3ad, and 3cd). If the substituent group was electron-
2
2
withdrawing group or electron-donating on the benzene
ring, the reactions could afford the desired products
in good yields. When heteroaryl acylazides 2eÀj derived
from the corresponding acyl chloride, such as 2-pyridine-
1
3c
in THF, reacted with 4-methylbenzoyl azide 2a in the
presence of CuCl to afford enamide 3aa in 72% isolated
yield (Scheme 2).
The extensive amidation reaction with 2a was conducted
1
17
18
carbonyl chloride, 2-thiophenecarbonyl chloride, and
2
3c,f
with variously fresh alkenylzirconocenes 1aÀl
and
individually to form their corresponding enamides 3aaÀla
19
-furancarbonyl chloride, were used, the corresponding
products 3aeÀcg were obtained in moderate yields. When
in the isolated yields between 45% to 88%, indicating the
alkylacyl azide 2h and benzylacyl azide 2i derived from
1
9
19
heptanoyl chloride and phenylacetyl chloride were
employed in the reaction, the expected enamides were
not obtained and starting materials remained. Cinnamoyl
(
(
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(
(
(20) Leading references: (a) Takahashi, T.; Kotora, M.; Kasai, K.;
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´
2005, 127, 8024. (h) Dufkov ꢀa , L.; Kotora, M.; Cısa ꢀr ov ꢀa , I. Eur. J. Org.
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(
(
1
which was detected by H NMR using mesitylene as an internal
standard.
B
Org. Lett., Vol. XX, No. XX, XXXX

a
Table 1. Amidation of Various Alkenylzirconocenes
Figure 1. Range of azide substrates.
a
Scheme 3. The Scope of Amidation with various Acyl Azides
a
Reaction conditions: alkenylzirconocene 1 prepared in situ from
alkyne (0.5 mmol) with zirconocene in 3 mL of THF solution, acyl azide
a
Reaction conditions: alkenylzirconocene 1 prepared in situ from
alkyne (0.5 mmol) with zirconocene in 3 mL of THF solution, acyl azide
2 (0.45 mmol), CuCl (0.55 mmol), N , 50 °C, protected from light, 12 h,
2
isolated yield based on acyl azide.
2
a (0.45 mmol), CuCl (0.55 mmol), N , 50 °C, protected from light, 12 h.
2
b
Isolated yield based on acyl azide.
Scheme 4. Possible Reaction Pathway
1
7
azide 2j derived from cinnamoyl chloride was used in the
reaction to afford the corresponding enamides 3cj and 3dj in
6
17
6% and 44% yield, respectively. Sulfonyl azide 2k could
also offer the corresponding enamide 3ck in 44% yield.
The plausible mechanism is proposed in Scheme 4. On the
base of the known transmetalation from the CÀZr to CÀCu
20
bond, the alkenylzirconocene 1 is first transmetalated with
CuCl to form an intermediate as the alkenylcopper 4. Then
10c
coordination of acyl azide to 4 forms the intermediate 5.
Rearrangement of 5 and a release of N forms the inter-
mediate 6, which is hydrolyzed to afford product 3.
2
Org. Lett., Vol. XX, No. XX, XXXX
C

In summary, a general copper-mediated amidation of
alkenylzirconocenes with acyl azides has been developed.
This reaction represents an interesting entry to the synth-
esis of enamides within a one-pot reaction from alkynes.
Supporting Information Available. Experimental pro-
13
1
cedures, full characterization including H NMR and
C
NMR data and IR data for all new compounds, copies
of spectra for all compounds, and the X-ray structure
of product 3da and X-ray data for 3da (CIF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. This work was supported by the
National Key Basic Research Program of China (973
program) (2012CB933402) and the National Natural
Science Foundation of China (21032004 and 21272132).
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX