Synthesis of triazoles from nonactivated terminal alkynes via the three-component coupling reaction using a Pd(0)-Cu(I) bimetallic catalyst

Article abstract of DOI:10.1021/ja034191s

The synthesis of triazoles via the three-component coupling reaction of unactivated terminal alkynes, allyl carbonate, and trimethylsiyl azide under the Pd(0)-Cu(I) bimetallic catalyst is developed. The reaction most probably proceeds through the formatio

Full text of DOI:10.1021/ja034191s

Published on Web 06/06/2003
Synthesis of Triazoles from Nonactivated Terminal Alkynes via the
Three-Component Coupling Reaction Using a Pd(0)-Cu(I) Bimetallic Catalyst
†
‡
‡
,‡
Shin Kamijo, Tienan Jin, Zhibao Huo, and Yoshinori Yamamoto*
Research Center for Sustainable Materials Engineering, Institute of Multidisciplinary Research for AdVanced
Materials, and Department of Chemistry, Graduate School of Science, Tohoku UniVersity, Sendai 980-8578, Japan
Received January 16, 2003; E-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
1
,2,3-Triazoles have found broad use in agrochemicals and
Scheme 1. The Synthesis of Triazoles via the [3 + 2]
Cycloaddition Reaction Using Activated Substrates
industrial applications such as dyes and corrosion inhibitors and
have also been regarded as an interesting unit in terms of biological
activity.1 Because of their potent usefulness, several synthetic
2
methods have been developed recently. The [3 + 2] cycloaddition
reaction between alkynes and azides is well investigated for the
construction of the triazole framework (Scheme 1): (1) the reaction
of alkynes having EWG (an electron-withdrawing group) with
3
simple azides, and (2) the reaction of simple alkynes with azides
4
having EWG. Accordingly, for the efficient [3 + 2] cycloaddition,
Table 1. Effect of Cu Additives on the Formation of the
Triazole 2aa
EWG is needed as a substituent either at the alkyne or at the azide
5
part. We now report that the synthesis of triazoles 3 from a simple
entry
additive
reaction time, h
GC yield (isolated), %b
alkyne and a simple azide is accomplished through the Pd(0)-
Cu(I) catalyzed three-component coupling (TCC) reaction between
alkynes 1, allyl methyl carbonate, and TMSN , followed by the
3
1
2
3
4
5
6
7
none
24
12
12
12
12
12
12
complex mixture
73 (66)
15
CuCl(PPh3)3
CuCl
CuI
12
deallylation of the resulting allyltriazoles 2 (eq 1). Here, the use of
c
Ph-CtC-Cu
78
6
the bimetallic catalyst, Pd(0)-Cu(I), is a key for promoting the
d
CuCl2
0
[3 + 2] cycloaddition (Scheme 2, Vide post).
Cu powder
trace
2 3
In the TCC reaction of phenylacetylene 1a using Pd (dba) ‚
CHCl catalyst, we surveyed the effect of Cu additives (Table 1).
3
The reaction without a copper additive gave a complex mixture of
products (entry 1). Among the Cu(I) additives we tested, CuCl-
a
The reaction of phenylacetylene 1a with allyl methyl carbonate (1.2
equiv) and TMSN3 (1.2 equiv) was carried out in the presence of
Pd2(dba)3‚CHCl3 (2.5 mol %), dppp (10 mol %), and an additive (20 mol
b
%
) in AcOEt (0.5 M) at 100 °C for the time indicated in Table 1. GC
(
PPh
3
)
3
gave the highest yield of 2a (entry 2). The addition of CuCl
yield using tetradecane as an internal standard. Isolated yield is shown in
parentheses. H NMR yield using p-xylene as an internal standard. The
starting alkyne 1a was recovered.
c 1
d
and CuI gave lower yields (entries 3 and 4). Copper(I) phenyl-
acetylide also showed a high catalytic activity for the formation of
2
a (entry 5). Other copper catalysts such as CuCl
were not effective (entries 6 and 7). Further optimization revealed
that the use of Pd (dba) ‚CHCl -P(OPh) catalyst combined with
increased the yield of the allyltriazole 2a, as mentioned
2
and Cu powder
Table 2. Synthesis of the Triazoles 2 under the Pd(0)-Cu(I)
Bimetallic Catalysta
yield, %b
2
3
3
3
entry
R
1
reaction time, h
2
CuCl(PPh
below.
3 3
)
1
2
3
4
5
6
7
8
9
Ph
1a
1b
1c
1d
1e
1f
1g
1h
1i
10
6
5
18
17
6
24
24
6
2a
2b
2c
2d
2e
2f
2g
2h
2i
83
78
72
63
66
77
63
58
75
56
54
50
59
p-Cl-C H4
p-MeO2C-C6H4
p-MeO-C6H4
p-Me2N-C6H4
1-naphthyl
6
CH3(CH2)5
t-Bu
PhSO2N(Me)CH2
BnOCH2
1-cyclohexenyl
isopropenyl
CH (CH ) -CtC
1
1
1
0
1
2
1j
1k
1l
6
2j
2k
2l
15
24
4
The TCC reactions with various terminal alkynes 1 are sum-
marized in Table 2. The reaction of phenylacetylene 1a with allyl
13
3
2 5
1m
2m
methyl carbonate and TMSN
3
was carried out in AcOEt at 100 °C
-CuCl(PPh catalyst system.
a
The reaction of the terminal alkynes 1 with allyl methyl carbonate (1.2
equiv) and TMSN3 (1.2 equiv) was carried out in the presence of
Pd2(dba)3‚CHCl3 (2.5 mol %), P(OPh)3 (20 mol %), and CuCl(PPh3)3 (10
mol %) in AcOEt (0.5 M) at 100 °C for the time indicated in Table 2.
under the Pd (dba) ‚CHCl -P(OPh)
2
3
3
3
3 3
)
The reaction was complete in 10 h to afford 2-allyl-4-phenyl-1,2,3-
triazole 2a in 83% yield (entry 1). The other aryl acetylenes 1b-e
gave the corresponding allyltriazoles 2b-e in good yields, respec-
tively (entries 2-5). 1-Naphthylacetylene 1f also produced the
triazole 2f in 77% yield (entry 6). The reactions of alkyl acetylenes,
such as octyne 1g and tert-butylacetylene 1h, afforded the desired
triazoles 2g and 2h in moderate yields (entries 7 and 8). The alkynes
b
Isolated yield.
1
i and 1j having a heteroatom substituent at the propargyl-position
gave the corresponding triazoles 2i and 2j in 75% and 56% yields,
respectively (entries 9 and 10). We then examined the reactions of
the conjugated enynes 1k and 1l (entries 11 and 12). The reaction
took place chemoselectively at the alkyne moiety to produce the
corresponding allyltriazoles 2k and 2l in moderate yields. The
†
Institute of Multidisciplinary Research for Advanced Materials.
Department of Chemistry.
‡
7786
9
J. AM. CHEM. SOC. 2003, 125, 7786-7787
10.1021/ja034191s CCC: $25.00 © 2003 American Chemical Society

C O MMU N I C A T I O N S
reaction of the conjugated diyne 1m proceeded at the terminal
alkyne moiety to give the triazole 2m in 59% yield (entry 13). The
structure of the 2-allyltriazole 2e was confirmed by X-ray crystal-
and efficient. For example, 2a was converted to 3a via the two-
step procedure (eq 4). The Ru-catalyzed isomerization provided
the propenyltriazole 2a′, and ozonolysis furnished the triazole 3a.
7
lographic analysis. It is clear that the allyl group is attached to the
central nitrogen in the triazole framework.
A plausible mechanism for the 2-allyltriazole forming reaction
under the Pd(0)-Cu(I) bimetallic catalyst is illustrated in Scheme
2
. At the initial stage of the catalytic cycle, the π-allylpalladium
8
azide complex A is formed with the extrusion of CO
TMSOMe via the reaction of Pd(0), allyl methyl carbonate, and
TMSN . At the same time, the copper-acetylide B would be formed
2
and
3
along with the generation of HCl via the reaction of the terminal
alkynes 1 and CuClLn. Next, [3 + 2] cycloaddition between the
azide moiety of the complex A and the C-C triple bond of the
copper-acetylide B takes place to form the intermediate C. Cu would
activate the C-C triple bond by forming a copper-acetylide species,
which makes the [3 + 2] cycloaddition feasible.2
a-b,9
The inter-
We are now in a position to synthesize various triazoles from
nonactivated terminal alkynes, which are not easily available from
the previously known methodologies. A key for this new transfor-
mation is to use the Pd(0)-Cu(I) bimetallic catalyst. The scope
and limitation of bimetallic catalyzed [3 + 2] cycloadditions and
extension of the TCC method to tetrazole synthesis are under
investigation.
mediate C would be in equilibrium with the intermediate E through
intervention of the (η -allyl)(η -triazoyl)palladium complex D.
Reductive elimination of Pd(0) from the intermediate E and the
protonolysis of the C-Cu bond by the terminal alkynes 1 or HCl
afford the 2-allyltriazoles 2.
3
5
10
Scheme 2. A Plausible Mechanism for the Formation of Triazoles
Supporting Information Available: Experimental procedures,
compound characterization data of 2a-n, 2a′, and 3a, and X-ray
crystallographic data of 2e (PDF and CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
2
under the Pd(0)-Cu(I) Bimetallic Catalyst
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(
(
(
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(
(
(
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4
7) See Supporting Information for detailed data.
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JA034191S
J. AM. CHEM. SOC.
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