Palladium-catalyzed alkenylation of 1,2,3-trizoles with terminal conjugated alkenes by direct C - H bond functionalization

Article abstract of DOI:10.1002/ejoc.200901282

A palladium-catalyzed alkenylation of 1,2,3-triazoles with terminal conjugated alkenes by direct C - H functionalization has been developed in the presence of Cu(OAc)2 and dioxygen. A variety of terminal alkenes such as acrylates and styrenes can perform the direct oxidative coupling reactions with 1,2,3-triazoles to afford the corresponding alkenylated products in 30-90% yield.

Full text of DOI:10.1002/ejoc.200901282

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200901282
Palladium-Catalyzed Alkenylation of 1,2,3-Trizoles with Terminal Conjugated
Alkenes by Direct C–H Bond Functionalization
Huanfeng Jiang,*[a] Zhenning Feng,[a] Azhong Wang,[a] Xiaohang Liu,[a] and
Zhengwang Chen[a]
Keywords: Palladium / Alkenylation / Nitrogen heterocycles / Alkenes / C–H functionalization
A palladium-catalyzed alkenylation of 1,2,3-triazoles with
terminal conjugated alkenes by direct C–H functionalization
has been developed in the presence of Cu(OAc)2 and di-
oxygen. A variety of terminal alkenes such as acrylates and
styrenes can perform the direct oxidative coupling reactions
with 1,2,3-triazoles to afford the corresponding alkenylated
products in 30–90% yield.
Introduction
Results and Discussion
Previous research on direct oxidative coupling revealed
that acetic acid was an effective solvent.[7,8a,12] In our initial
experiment, when a mixture of 1-octyl-4-phenyl-1H-1,2,3-
triazole (1a), methyl acrylate (2a), Pd(OAc)2 (10 mol-%),
and Cu(OAc)2 (20 mol-%) was heated at 110 °C in AcOH
under 8 atm O2 in an autoclave, no desired product was
detected and 1a was 100% recovered (Table 1, Entry 1).
Interestingly, replacement of HOAc with dioxane led target
molecule 1,4,5-trisubstituted-1H-1,2,3-triazole (3aa) in a
low yield (Table 1, Entry 2), and the yield of 3aa increased
to 83% when we increased the amount of Cu(OAc)2 to
2 equivalents (Table 1, Entry 3). Reducing the amount of
Pd(OAc)2 decreased the yield (Table 1, Entry 4). Employing
other palladium catalysts, such as PdCl2 and Pd(dba)2, also
decreased the yields (Table 1, Entries 5 and 6). We also
found that the yield decreased without O2 (Table 1, En-
1,2,3-Triazoles are one of the most important N-hetero-
cyclic compounds in organic chemistry due to their inimi-
table chemical and structural properties, as well as their
wide application in agrochemicals and industry such as dyes
and corrosion inhibitors.[1] Since Meldal and Sharpless
pioneered the copper-catalyzed Huisgen’s 1,3-dipolar [3+2]
cycloadditions of azides with alkynes to construct 1,4-di-
substituted 1,2,3-triazoles,[2] the synthesis of highly substi-
tuted 1,2,3-triazoles has been of great interest. Known
methods for their preparation include transition-metal-cata-
lyzed C-5 functionalization with Pd[3,4a,4b] and Cu[4c] and
Heck-type reactions of prefunctionalized 5-iodo-1,2,3-tri-
azoles with alkenes.[5] To the best of our knowledge, there
are no examples of the direct alkenylation of 1,2,3-tri-
azoles.[6]
Palladium-catalyzed alkenylation of arenes by C–H bond try 7). Replacement of Cu(OAc)2 with AgOAc, FeCl3, or
activation has become a hot topic in recent years.[7] This DDQ resulted in only trace amounts of the products
method is highly atom economic and has been utilized in (Table 1, Entries 8–10). The addition of base did not pro-
intramolecular and intermolecular direct oxidative alkenyl- mote the coupling reaction under our conditions (Table 1,
ation of arenes, thiophenes, furans,[8] indoles, pyrroles,[9] Entries 11–15). The reaction did not proceed in the absence
and pyrazoles.[10,11] These facts prompted us to investigate of Pd(OAc)2 (Table 1, Entry 16).
the possibility of alkenylation of 1,2,3-triazoles with alkenes
With the optimized conditions in hand [10 mol-%
by C–H bond activation. Herein, we report direct oxidative Pd(OAc)2, 2 equiv. of Cu(OAc)2, 110 °C in dioxane under
alkenylation in the presence of a Pd(OAc)2/Cu(OAc)2/O2 8 atm O2], we probed the scope of the direct alkenylation
catalytic system for the preparation of highly substituted of 1,2,3-triazoles with different alkenes. The results are
1,2,3-triazoles.
summarized in Table 2. At first, we examined a variety of
1,2,3-triazoles and methyl acrylate was utilized as the sub-
strate (Table 2, Entries 1–8). 1,2,3-Triazoles bearing large
R2 groups were shown to have a steric effect on the yields.
A gradual increase in yield was accompanied by a decrease
in the size of the R2 group (Table 2, Entries 1–3 and 4, 5).
Aromatic rings with electron-donating R1 groups led to
moderate yields, which indicated the electronic effect of the
[a] School of Chemistry and Chemical Engineering, South China
University of Technology,
Guangzhou 510640, P. R. China
Fax: +86-020-87112906
E-mail: jianghf@scut.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901282.
Eur. J. Org. Chem. 2010, 1227–1230
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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H. Jiang, Z. Feng, A. Wang, X. Liu, Z. Chen
Table 1. Optimization of reaction conditions for the Pd-catalyzed alkenylation of 1a with 2a.[a]
SHORT COMMUNICATION
Entry
Catalyst
Additive
Solvent
Yield[%][b]
1
2
3
4
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
5 mol-% Pd(OAc)2
10 mol-% Pd(dba)2
10 mol-% PdCl2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
10 mol-% Pd(OAc)2
–
20 mol-% Cu(OAc)2
20 mol-% Cu(OAc)2
2 equiv. Cu(OAc)2
2 equiv. Cu(OAc)2
2 equiv. Cu(OAc)2
2 equiv. Cu(OAc)2
2 equiv. Cu(OAc)2
2 equiv. AgOAc
HOAc
n.r.[c]
16
83 (80)
59
29
72
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
5
6
7[d]
8
18
trace
n.r.[c]
trace
32
9
2 equiv. FeCl3
2 equiv. DDQ
10
11
12
13
14
15
16
20 mol-% Cu(OAc)2 /2 equiv. K2CO3
2 equiv. Cu(OAc)2 /2 equiv. K2CO3
2 equiv. Cu(OAc)2 /2 equiv. NaOAc
2 equiv. Cu(OAc)2 /2 equiv. KOH
2 equiv. Cu(OAc)2 /2 equiv. DBU
2 equiv. Cu(OAc)2
75
80
n.r.[c]
n.r.[c]
n.r.[c]
[a] Reaction conditions: 1,2,3-triazole (0.3 mmol), methyl acrylate (0.6 mmol, 2 equiv.), solvent (2 mL), 110 °C, 8 atm O2, 20 h. [b] Deter-
mined by GC. [c] No reaction. [d] Without O2.
substrate (Table 2, Entries 4–6). The yield decreased to 56%
when an electron-withdrawing group was present as R1 on
the aromatic ring (Table 2, Entry 7). Substrates with alkyl
groups as R1 also afforded products in moderate yield
(Table 2, Entry 8). On the other hand, when less reactive
alkenes such as styrene were chosen, homocoupling by-
products were generated under the same reaction condi-
tions. The yields of the desired products were low until we
Scheme 1. Palladium-catalyzed alkenylation of monosubstituted
increased the reaction time to 40 h (Table 2, Entries 10–14).
There are similar steric and electronic effects on the forma-
tion of 3ca, 3cc, and 3cd, resulting in yields of 61, 44, and
39%, respectively (Table 2, Entries 10–12). 1-Fluoro-4-
vinylbenzene afforded the product in a yield of 51%, be-
cause the electron-withdrawing group might improve the
activity of styrene (Table 2, Entry 13). 1-Methyl-4-vinylben-
zene seemed less susceptible than 1-fluoro-4-vinylbenzene
triazoles.
Although a detailed mechanism still remains elusive, we
to undergo the reaction, which led to a lower yield of 3eh. propose a reaction path similar to that proposed by Fuji-
Finally, we employed other terminal alkenes such as acrylo- wara (Scheme 2).[7b] Initially, electronic attack of PdII on
nitrile and acrylamide, but only trace amounts of products the triazole forms intermediate A. Active intermediate A
were detected by GC–MS. In addition, internal alkenes like then inserts into the alkene to form intermediate B, which
methyl but-2-enoate or ethyl cinnamate were not suitable rapidly decomposes through β-elimination to afford the tar-
for the reaction. This suggested the substituted group on get products and an active palladium species. More recently,
the C–C double bond inhibited the reaction. Finally, we Ishii reported a new hydropalladation mechanism in a re-
increased the scale of the reaction to 1 mmol, and the yield lated coupling reaction, and this may also explain our reac-
of 3aa decreased slightly, but an acceptable result of 71% tion. (Scheme 2, path B).[12b]According to the mechanism
was still obtained.
of Ishii, vinyl palladium species AЈ is formed by the vinyl
In order to examined the regioselectively of the triazoles, species and Pd(OAc)2. Then, insertion into the Pd–vinyl
N-monosubstituted triazole 1j was used as a substrate bond leads to σ-Pd complex BЈ, and after β-elimination the
(Scheme 1). To our delight, highly regioselective 1,5-disub- same products as those afforded in Path A are obtained.
stituted triazole 3aj was the major product along with only Finally, Pd0 is recycled by the cooperation of CuII and O2.
trace amounts of the fully substituted triazole.[13] These re- According to the result in Table 1, a higher pressure of O2
sults are similar to those reported.[3,4b]
may promote the regeneration of CuII from CuI.
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Eur. J. Org. Chem. 2010, 1227–1230

Pd-Catalyzed Alkenylation of 1,2,3-Trizoles
Table 2. Pd-catalyzed coupling of 1,4-disubstituted-1H-1,2,3-triazoles with alkenes.[a]
[a] Reaction conditions: triazole (0.3 mmol), alkene (0.6 mmol, 2 equiv.), dioxane (2 mL), Pd(OAc)2 (10 mol-%), Cu(OAc)2 (2 equiv.),
110 °C, 8 atm O2, 20 h. [b] Isolated yields. [c] After 40 h. [d] When using acrylate as alkene, no more than 3% of the (Z) diastereomer
was detected by GC–MS, whereas, when styrene derivatives were used the alkene, the (E) diastereomer was exclusively formed.
were referenced to TMS. GC–MS was obtained by using electron
ionization (EI). TLC was performed by using commercially pre-
pared 100–400 mesh silica gel plates (GF254), and visualization was
effected at 254 nm. All the other chemicals were purchased from
Conclusions
In summary, we have developed an efficient and new
method for the palladium-catalyzed dehydrogenative cou-
pling of triazoles and terminal alkenes. The method pro- Aldrich Chemicals.
vides trisubstituted 1,4,5-trisubstituted-1H-1,2,3-triazoles
Typical Experimental Procedure for Pd-catalyzed Alkenylation of 1a
in reasonable to excellent yields and with high regio- and
stereoselectivities. It should be mentioned that these highly
substituted-1H-1,2,3-triazoles might show potential bio-
logical activities and be utilized in agrochemical and phar-
maceutical industries.
with 2a: A mixture of 1-octyl-4-phenyl-1H-1,2,3-triazole (1a;
77.1 mg, 0.3 mmol), methyl acrylate (2a; 51.6 mg, 0.6 mmol),
Pd(OAc)2 (6.7 mg, 0.03 mmol), and Cu(OAc)2 (108.9 mg,
0.6 mmol) in dioxane (2 mL) was added to a HF-10 autoclave, and
then oxygen gas was pumped into the autoclave by a cooling pump
until the desired pressure (8 atm) was reached. The autoclave was
heated at 110 °C by oil bath under magnetic stirring for the desired
time. After the reaction finished, the autoclave was allowed to cool
to room temperature. O2 was vented and the surplus was filtered
and condensed under reduced pressure. The solvent was subjected
Experimental Section
General: 1H NMR spectra were recorded in CDCl3 at 400 MHz
and 13C NMR spectra were recorded at 100 MHz; chemical shifts
Eur. J. Org. Chem. 2010, 1227–1230
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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H. Jiang, Z. Feng, A. Wang, X. Liu, Z. Chen
SHORT COMMUNICATION
Scheme 2. Plausible reaction pathway for the alkenylation of triazoles.
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to isolation by TLC (GF254), eluting with petroleum ether/dichloro-
methane to give compound 3aa. 1H NMR (400 MHz, CDCl3,
25 °C): δ = 0.86 (t, JH,H = 6.8 Hz, 3 H, 3-CH2CH3), 1.23–1.37
(m, 10 H, 10ϫCH2CH2CH2CH2CH2CH3), 1.90–1.93 (m, 2 H, 2-
CH2CH2C6H13), 3.78 (s, 3 H, 3-OCH3), 4.43 (t, JH,H = 7.4 Hz, 2
H, 2-NCH2), 6.31 (d, JH,H = 16.4 Hz, 1 H, CH=CHCOOCH3),
7.37–7.46 (m, 3 H, 3-C6H5), 7.61–7.63 (m, 2 H 2-C6H5), 7.62 (d,
JH,H
= 16.4 Hz, 1
H, CH=CHCOOCH3) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 14.0, 22.6, 26.5, 28.9, 29.0, 30.0,
31.7, 49.3, 52.1, 122.6, 126.7, 127.7, 128.0, 128.2, 128.4, 128.6,
128.8, 128.9, 130.6, 147.8, 166.3 ppm. MS (EI, 70 eV): m/z (%) =
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341 (5) [M]+, 213 (100), 228 (36). IR (KBr): ν = 3029, 2925, 2858,
˜
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C20H27N3O2 (341.06): calcd. C 70.35, H 7.97, N 12.31; found C
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Supporting Information (see footnote on the first page of this arti-
cle): Analytical and spectroscopic data for compounds 3aa–3aj.
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Acknowledgments
We thank the National Natural Foundation of China (Nos.
20625205, 20772034, and 20932002) and Guangdong Natural Sci-
ence Foundation (No. 07118070) for financial support.
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[13] The structure of 3aj was determined by NOESY. See Support-
ing Information for details.
Received: November 9, 2009
Published Online: January 20, 2010
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Eur. J. Org. Chem. 2010, 1227–1230