Regiospecific synthesis of 2-allyl-1,2,3-triazoles by palladium-catalyzed 1,3-dipolar cycloaddition

Article abstract of DOI:10.1016/S0040-4039(02)02206-2

2-Allyl-1,2,3-triazoles were prepared by the palladium-catalyzed three component coupling (TCC) reaction of alkynes, allyl methyl carbonate and trimethylsilyl azide. A π-allylpalladium azide complex, which undergoes the 1,3-dipolar cycloaddition with alkynes, is proposed as a key intermediate in the TCC reaction.

Full text of DOI:10.1016/S0040-4039(02)02206-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9707–9710
Regiospecific synthesis of 2-allyl-1,2,3-triazoles by
palladium-catalyzed 1,3-dipolar cycloaddition
Shin Kamijo,a Tienan Jin,b Zhibao Huob and Yoshinori Yamamotob,*
aResearch Center for Sustainable Materials Engineering, Institute of Multidisciplinary Research for Advanced Materials,
Tohoku University, Sendai 980-8578, Japan
bDepartment of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Received 22 August 2002; revised 25 September 2002; accepted 4 October 2002
Abstract—2-Allyl-1,2,3-triazoles were prepared by the palladium-catalyzed three component coupling (TCC) reaction of alkynes,
allyl methyl carbonate and trimethylsilyl azide. A p-allylpalladium azide complex, which undergoes the 1,3-dipolar cycloaddition
with alkynes, is proposed as a key intermediate in the TCC reaction. © 2002 Published by Elsevier Science Ltd.
1,2,3-Triazoles are important substrates because of
their wide use.1 They have been considered as an inter-
esting component in terms of biological activity and are
seen in many drugs.2 1,2,3-Triazole heterocycles have
also found broad use in industrial applications1b such
as dyes and brighteners for fibers, corrosion inhibitors
for many metals and alloys, light stabilizers for organic
materials and polymers, and agrochemicals as herbi-
cides, fungicides and antibacterial agents. More
recently, 1,2,3-triazoles have been used as a backbone
of a bidentate phosphine ligand and several new com-
plexes have been synthesized.3
procedure, although several new and useful methodolo-
gies have been developed quite recently.5 Usually, when
an organic azide is reacted with a nonsymmetrical
acetylene as the dipolarophile, a mixture of 1-substi-
tuted and 3-substituted-1,2,3-triazoles is obtained as
shown in Eq. (1).1,4c An alternative procedure for the
preparation of N-substituted-1,2,3-triazoles is shown in
Eq. (2), in which the introduction of the substituent is
carried out after the formation of the 1,2,3-triazole.1,4c
However, the reaction of organic halides with 1,2,3-tri-
azoles under basic conditions gives a mixture of 1-sub-
stituted and 3-substituted-1,2,3-triazoles in most cases.6
(1)
(2)
1,3-Dipolar cycloadditions are well-studied reactions
and a wide variety of 1,3-dipoles have been developed.4
It is well known that the 1,3-dipolar cycloaddition
between azides and alkynes is a useful procedure for the
preparation of 1,2,3-triazoles. However, we encoun-
tered difficulty when we planned to synthesize regiose-
lectively N-alkyl-substituted 1,2,3-triazoles through this
We now report that the palladium-catalyzed three com-
ponent coupling (TCC) reaction of alkynes, allyl car-
bonate and trimethylsilyl azide results in the
regiospecific formation of 2-allyl-1,2,3-triazoles (Eq.
(3)). This palladium-catalyzed TCC reaction allows us
to prepare 2-allyl-1,2,3-triazoles selectively, which are
not easily obtained via known methods.
The results of the palladium-catalyzed TCC reaction
for the regioselective formation of 2-allyl-1,2,3-triazoles
* Corresponding author. Tel.: +81-22-217-6581; fax: +81-22-217-6784;
e-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
0040-4039/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(02)02206-2

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S. Kamijo et al. / Tetrahedron Letters 43 (2002) 9707–9710
(3)
are summarized in Table 1. We first found that the
TCC reaction with the electron-deficient alkyne 1a,
which is conjugated with a cyano group, gave the
allyltriazole 2a. Encouraged by this result, we optimized
the reaction conditions. A representative procedure is
as follows. Allyl methyl carbonate (1.2 equiv.) and
trimethylsilyl azide (1.2 equiv.) were added to a solu-
tion of cyano phenyl acetylene 1a, Pd2(dba)3·CHCl3
went the cycloaddition, but the corresponding allyltria-
zole 2g was obtained in only 33% yield (entry 7). We
next investigated the reaction of various alkynyl methyl
ketones 1h–k in which R1 is H, Et, cyclohexenyl, or
t-Bu. The reaction of the terminal alkyne 1h and ethyl-
substituted internal alkyne 1i produced the allyltriazoles
2h and 2i, respectively, in moderate to good yields
(entries 8 and 9). In the case of an alkyne conjugated
with an alkenyl group 1j, the reaction took place
chemoselectively at the alkyne moiety to produce the
corresponding allyltriazole 2j (entry 10). Even the steri-
cally hindered tert-butyl-substituted alkyne 1k gave the
allyltriazole 2k in good yield (entry 11). The above
results indicate that the reaction proceeds irrespective
of the substituent R1. On the contrary, the yields of the
allyltriazoles 2l and 2m were less in the cases of the
alkynes 1l and 1m having an ester as an electron-with-
drawing group (entries 12 and 13). However, the intro-
duction of two ester groups at both termini of the triple
bond resulted in enhancement of the reactivity; the
reaction of dimethyl acetylenedicarboxylate 1n gave the
corresponding allyltriazole 2n in 60% yield within 2 h
(entry 14). The alkyl-substituted alkynyl aldehyde 1o
afforded the corresponding allyltriazole 2o in moderate
yield (entry 15).
(2.5
mol%)
and
dppp
(1,3-bis(diphenylphos-
phino)propane) (10 mol%) in AcOEt (0.5 M). The
mixture was stirred at 100°C for 2 h. After the starting
acetylene was consumed, the mixture was cooled down
to rt and filtered through a Florisil short column.
Purification on a silica gel column (hexane/toluene 1:1–
1:2) afforded 2-allyl-4-cyano-5-phenyl-1,2,3-triazole 2a
in 50% yield (entry 1). We further carried out the
reactions of alkynes 1b–f conjugated with various elec-
tron-withdrawing groups. The reaction of the alkynyl
aldehyde 1b and ketone 1c proceeded smoothly to
afford the corresponding allyltriazoles 2b and 2c,
respectively, in moderate yields (entries 2 and 3). The
reaction of the alkynyl ester 1d and phosphonate 1e
also produced the allyltriazoles 2d and 2e, respectively,
in moderate yields though longer reaction times were
needed (entries 4 and 5). The reaction of the alkynyl
sulfone 1f proceeded smoothly and was complete in 3 h;
however, the allyltriazole 2f was obtained in a lower
yield (entry 6). An alkyne having an electron-donating
group such as the diethylamino group 1g also under-
The structures of the products were determined by the
detailed analyses of the spectroscopic data of the allyl-
1
triazoles 2. The H and 13C NMR data of allyltriazole
Table 1. Palladium-catalyzed formation of 2-allyl-1,2,3-triazolesa
Entry
R1
R2
1
Reaction time (h)
2
Yield (%)b
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
CN
CHO
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
2
2
2
24
24
3
2
2
2
4
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
50
55
56
53
53
29
33
66
56
61
65
24
15c
60
53
COMe
CO2Me
P(O)(OEt)2
SO2Ph
NEt2
COMe
COMe
COMe
COMe
CO2Me
CO2Me
CO2Me
CHO
9
Et
10
11
12
13
14
15
1-Cyclohexenyl
tBu
4
H
24
24
2
CH3(CH2)5
CO2Me
CH3(CH2)4
3
a Allyl methyl carbonate and Me3SiN3 were added to a solution of the alkyne 1, Pd2(dba)3·CHCl3 (2.5 mol%) and dppp (10 mol%) in AcOEt. The
mixture was stirred at 100°C for the time shown in Table 1.
b Isolated yields.
c The starting alkyne 1i was recovered in 13% yield.

S. Kamijo et al. / Tetrahedron Letters 43 (2002) 9707–9710
9709
Scheme 1. Proposed mechanism for the formation of 2-allyl-1,2,3-triazoles.
2n indicated that the product had a symmetrical struc-
ture.7 Furthermore, the position of the allyl group was
unambiguously confirmed by conducting NOE experi-
ments on compound 2h.8
synthetic applications of p-allylpalladium azide com-
plexes are in progress in our laboratory.
Acknowledgements
A proposed mechanism for the formation of 2-allyl-
1,2,3-triazoles via the palladium-catalyzed TCC reac-
tion is shown in Scheme 1. The reaction of allyl methyl
carbonate, trimethylsilyl azide and Pd(0) produces the
p-allylpalladium azide complex A9,10 with concomitant
evolution of CO2 and trimethylsilyl methoxide in the
first step of the catalytic cycle. Then, the 1,3-dipolar
cycloaddition of the azide moiety of the complex A
with the alkyne 1 forms the 1-(h3-allylpalladium)-1,2,3-
triazole complex B. The complex B will be in equi-
librium with the 2-(h3-allylpalladium)-1,2,3-triazole D
through the formation of the (h3-allyl)(h5-tria-
zoyl)palladium complex C, an analogue of the (h3-
allyl)(h5-cyclopentadienyl)palladium complex.11 Regen-
eration of Pd(0) by reductive elimination from the
complex D affords the 2-allyltriazole 2.
We acknowledge faculties in the Instrumental Analysis
Center for Chemistry at Tohoku University for the
measurements of NMR spectra, mass spectra and ele-
mental analyses.
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9710
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