Synthesis of allenes through triazole gold(III) catalysed rearrangement of propargyl vinyl ethers

Article abstract of DOI:10.3184/174751916X14754985053189

An efficient and simple method to the synthesis of allene derivatives was developed through pyridyltriazole gold(III) catalysed rearrangement of propargyl vinyl ethers with moderate to good yields. It was found that the pyridyltriazole gold(III) complex is a good chemoselective catalyst in selective activation of alkynes and allenes. Compared to gold(I) catalysts, the pyridyltriazole gold(III) shows much better substrate tolerance and much higher air and moisture stability.

Full text of DOI:10.3184/174751916X14754985053189

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 NOVEMBER, 645–647
RESEARCH PAPER 645
Synthesis of allenes through triazole gold(III) catalysed rearrangement of
propargyl vinyl ethers
Dawei Wang*, Yongchun Yang, Ronghui Huang, Likui Wang and Huida Wan
The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122,
Jiangsu Province, P.R. China
An efficient and simple method to the synthesis of allene derivatives was developed through pyridyltriazole gold(III) catalysed
rearrangement of propargyl vinyl ethers with moderate to good yields. It was found that the pyridyltriazole gold(III) complex is a good
chemoselective catalyst in selective activation of alkynes and allenes. Compared to gold(I) catalysts, the pyridyltriazole gold(III) shows
much better substrate tolerance and much higher air and moisture stability.
Keywords: pyridyltriazole, allene, propargyl vinyl ethers, rearrangement, alkynes
The efficient preparation and reactions of valuable heterocyclic
architectures containing diversification sites constitute major
challenges in organic chemistry.1 For example, 3,4-fused
tricyclic indole skeletons, 1,2-oxathiane 2,2-dioxides, pyrrolin-
2-one skeletons and pyran structures are featured in plenty
of natural products and biologically active drug candidates.
Some of these skeletons or heterocycles have significant
pharmaceutical activities and exhibit a wide range of biological
activities such as antidiabetic, inhibitory, and antiviral
activities.2–5 The synthesis of these functional molecules from
allenes is an important strategy.6 However, it is not easy to obtain
these allenes; indeed, it is a very challenging task. Among the
possibilities, gold(I)-catalysed rearrangement of alkynes is an
interesting and useful method for allene synthesis. However,
gold usually activates allenes further and it is difficult to retain
the products at the allene stage.7,8 Toste et al. reported that
[(Ph3PAu)3O)]BF4 catalysed propargyl Claisen rearrangements
in the synthesis of allenes with good yields.9–11 The Nolan group
showed that [(IPr)Au(pyr)][BF4] was an effective catalyst
for allene synthesis.12 Shi et al. found that triazole-gold TA-
Au(I) complexes are very effective chemoselective catalysts
in promoting propargyl ester/ether 3,3-rearrangements and
resulted in chirality transfer without racemisation over a
long period of time, affording enantioenriched allenes with
excellent stereoselectivity.13–18 Later, Shi et al. developed a
highly efficient synthesis of substituted conjugated dienals via
triazole−gold-catalysed propargyl vinyl ether rearrangement
and an amine catalysed allene−aldehyde tautomerisation.19
They described intermolecular propargyl alcohol addition to
alkynes as a general approach for the synthesis of substituted
allenones using triazole-gold(I) (TA-Au) conditions.20
Substituted bicyclic [4.4.0]dihydronaphthalene compounds
were also synthesised through gold-catalysed rearrangement
of propargyl esters followed by allene–ene cyclisation.21
Hiersemann et al. reported the Gosteli–Claisen rearrangement
of 2-alkoxycarbonyl-substituted propargyl vinyl ethers to afford
γ-allenyl-α-keto esters, substituted furans and cyclopentenes.22
Liu and Cheng described the gold(I)-catalysed propargyl
Claisen rearrangement/6-endo-trig cyclisation of propargyl
vinyl ethers in preparation of bicyclic furopyran derivatives.23
with good E-/Z-selectivity.25 However, this gold(III) complex
is not well studied and some other transformations need
further exploration. In this paper, we report the TA-Py-Au(III)
catalysed rearrangement of propargyl vinyl ethers in synthesis
of allenes with moderate to good yields (Scheme 1). This is a
good example of gold(III) catalysed rearrangement of propargyl
vinyl ethers.
Results and discussion
In light of the above considerations, we initially investigated the
rearrangement of propargylic esters in the synthesis of allenes.
The substrates, propargylic ester 1, which were easily prepared
in high yields, was chosen as a reaction model to test reaction
with 2 mol% TA-Py-Au(III) (Scheme 2). However, only a
mixture of compounds 2 and 3 were obtained, even with a range
of solvents such as CH2Cl2, CH3CN, 1,4-dioxane, acetone,
toluene, THF and MeOH. This revealed that TA-Py-Au(III) is
not suitable for allene synthesis using propargyl esters.
To our delight, employing a propargyl vinyl ether 4a allowed
the clean formation of 5a with enhanced yield. Impressively,
5a was obtained in good yield when dry dichloromethane was
used (Table 1, entry 8). When the reaction was performed in
the absence of catalyst (entry 10) no product was observed
thus demonstrating the necessity of the gold catalyst. It should
be noted the reaction did not happen with AuCl3 as a catalyst
(Table 1, entry 9).
Our previous work
R1
O
OH
+
TA-Py-Au(III)
NXS
R1
N
N
R3
R2
Cl
R3
N
Cl-
R2
X
Au
N
Cl
X = I, Br, Cl
This work
O
TA-Py-Au III
(
)
•
Ar
OH
TA-Py-Au(III)
Ar
Bu
Bu
Scheme 1 TA-Py-Au(III) catalysed reactions.
OAc
O
TA-Py-Au(III)
DCM
•
OAc
They reported
a gold(I)-catalysed nucleophile-mediated
Bu
+
Bu
method for stereoselective synthesis of bicyclic furan and pyran
Bu
derivatives with moderate to good yields.24
1
2
3
reaction mixture
Recently, we developed a pyridyltriazole gold(III) complex
(TA-Py-Au) as an effective catalyst for α-haloenone synthesis
Scheme 2 The rearrangement of propargyl esters.
* Correspondent. E-mail: wangdw@jiangnan.edu.cn

646 JOURNAL OF CHEMICAL RESEARCH 2016
Table 1 Optimisation of reaction conditionsa
Table 2 Substrate experiments of propargylic ethersa,b
O
O
•
•
OH
TA-Py-Au,
OH
1)
rt
1) TA-Py-Au DCM, rt
2) NaBH4, MeOH, rt
R
2) NaBH4, MeOH, rt
Bu
R
Bu
Bu
Bu
5
4a
5a
4
HO
F
HO
NO2
HO
Entry
1
Solvent
MeCN
Conversion
Yield of 5a/%b
•
•
•
5
13
3
-
Bu
83%
Bu
5b 77%
Bu
2
1,4-dioxane
acetone
MeOH
:
:
:
5c
5a
80%
HO
•
3
21
7
7
HO
HO
•
Cl
4
-
Cl
•
5
DCM
83
5
72
4
Bu
81%
HO
Bu
Bu
6
toluene
:
:
:
5f
5d
5e
79%
HO
74%
HO
7
THF
<5
>95
<5
<5
>95
92
-
OMe
•
•
•
8
DCM(dry)
DCM(dry)
DCM(dry)
DCM(dry)
DCM(dry)
83
c
9
-
Bu
Bu
MeO
Bu
Cl
d
10
11
12
-
:
:
:
5i
72%
5g
5h
75%
76%
81e
78f
aConditions: 4 (1.0 mmol), TA-Py-Au(III) (2 mol%), dry CH2Cl2 (4 mL), r.t., 3–5 h.
bIsolated yields based on 4.
aConditions: TA-Py-Au(III) (2 mol%), 4a (1.0 mmol), solvent (4 mL), 4 h.
bIsolated yields based on 4a, “-” means “no product was observed”.
cAuCl3 was used.
Experimental
dNo catalyst.
Synthesis of allenes (5a-i); general procedure
eTA-Py-Au(III) (1 mol%).
To a solution of the appropriate propargyl vinyl ether 4 (1 mmol) in
dry CH2Cl2 (4.0 mL, 0.25 M), was added TA-Py-Au(III) (2 mol%) at
RT. The reaction mixture was kept at room temperature and monitored
by TLC. After the reaction was completed (3–5 h), NaBH4 (1.5 mmol)
and MeOH (0.5 mL) was added to the mixture. After the reaction
was finished (monitored by TLC), the solvent was removed under
reduced pressure and purification of the crude product by column
chromatography on silica-gel (petroleum ether/ethyl acetate, 80:1)
afforded compound 5.
3-[2-(o-Tolyl)vinylidene]heptan-1-ol (5a)13: Colourless oil; yield
83%; 1H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 7.2 Hz, 1H), 7.18–7.07
(m, 3H), 6.40–6.37 (m, 1H), 3.80 (dd, J = 10.8, 5.2 Hz, 2H), 2.45–2.30
(m, 5H), 2.19–2.06 (m, 2H), 1.65–1.30 (m, 5H), 0.91 (t, J = 7.2 Hz, 3H);
13C NMR (101 MHz, CDCl3): δ 202.6, 134.8, 133.4, 130.6, 126.7, 126.6,
126.2, 104.7, 93.2, 61.0, 35.9, 32.8, 29.8, 22.5, 19.8, 13.9.
3-[2-(2-Fluorophenyl)vinylidene]heptan-1-ol (5b)13: 1H NMR
(400 MHz, CDCl3): δ 7.36 (td, J = 7.2, 1.2 Hz, 1H), 7.18–7.10 (m,
1H), 7.10–6.98 (m, 2H), 6.45–6.37 (m, 1H), 3.78 (t, J = 6.4 Hz, 2H),
2.41–2.32 (m, 2H), 2.16–2.05 (m, 2H), 1.63 (s, 1H), 1.53–1.30 (m, 4H),
0.90 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 202.8 (d, J =
2.0 Hz), 161.0 (d, J = 249.8 Hz), 128.0 (d, J = 8.2 Hz), 127.9 (d, J = 3.6
Hz), 124.2 (d, J = 3.5 Hz), 122.9 (d, J = 11.8 Hz), 115.8 (d, J = 21.6 Hz),
105.5, 88.5 (d, J = 6.4 Hz), 60.8, 35.9, 32.6, 29.7, 22.4, 13.9.
fTA-Py-Au(III) (0.5 mol%), 12 h.
With the optimised conditions in hand, the substrate
scope of this TA-Py-Au(III) catalysed propargyl vinyl
ethers rearrangement was further investigated, the results
are summarised in Table 2. We set out to examine the effect
of substituents on the aryl moiety in the reaction. The results
showed that substrates bearing electron-donating or electron-
withdrawing groups have little influence on the reaction
outcome. For example, the reactions proceeded smoothly to
afford the corresponding allene 5 in moderate to good yields,
when the R group of propargyl vinyl ethers 4 was the electron-
donating methyl substituent or the electron-deficient 5-fluoro
and 5-chlorosubstituents groups. It also should be noted that the
presence of a substituent at the ortho-, meta- or para-positions
did not affect the reaction. Compared to the earlier method with
TA-Au(I) as a catalyst,13 this methodology has much better
substrate tolerance. Substrates with the substituents NO2, OMe,
Cl and F could be converted into allene products smoothly
without increasing catalyst loading, while some other substrates
needed enhanced catalyst loading.13 It should be noted that quite
a good yield was obtained even with a reduced catalyst loading
(Table 1, entries 11–12). Another point is that the complex TA-
Py-Au(III) has much higher air and moisture stability, which
means this transformation could take place in the air without
yields decreasing. This might be attributed to the better stability
of the TA-Py-Au(III) complex, which is stabilised by both the
triazole and pyridine units. Thus no reduction in the catalytic
activity of the gold complex was observed. All the data indicates
that TA-Py-Au(III) is a good choice for the preparation of
allenes and is therefore a better chemoselective catalyst.
3-[2-(2-Nitrophenyl)vinylidene]heptan-1-ol (5c)13: 1H NMR (400
MHz, CDCl3): δ 7.88 (dd, J = 8.0, 1.2 Hz, 1H), 7.60 (dd, J = 8.0, 1.2 Hz,
1H), 7.48 (td, J = 7.2, 1.2 Hz, 1H), 7.34–7.26 (m, 1H), 6.86–6.80 (m,
1H), 3.80 (t, J = 6.0 Hz, 2H), 2.44–2.35 (m, 2H), 2.20–2.10 (m, 2H),
1.65 (s, 1H), 1.53–1.32 (m, 4H), 0.90 (t, J = 7.2 Hz, 3H);13C NMR (101
MHz, CDCl3): δ 204.5, 147.4, 132.7, 130.5, 129.1, 127.1, 124.8, 106.6,
91.0, 60.7, 35.6, 32.3, 29.6, 22.4, 13.9.
3-[2-(2-Chlorophenyl)vinylidene]heptan-1-ol (5d)13: H NMR (400
1
MHz, CDCl3): δ 7.45 (dd, J = 7.6, 1.2 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H),
7.20 (t, J = 7.2 Hz, 1H), 7.10 (td, J = 7.6, 1.2 Hz, 1H), 6.70–6.60 (m,
1H), 3.78 (t, J = 6.0 Hz, 2H), 2.45–2.30 (m, 2H), 2.20–2.08 (m, 2H),
1.72 (d, J = 22.0 Hz, 1H), 1.55 – 1.43 (m, 2H), 1.42–1.33 (m, 2H), 0.90
(t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 203.1, 133.0, 132.0,
129.8, 127.8, 127.7, 126.8, 105.9, 92.3, 60.8, 35.8, 32.6, 29.7, 22.5, 13.9.
3-[2-(2-Chlorophenyl)vinylidene]heptan-1-ol (5e)13: H NMR (400
MHz, CDCl3): δ 7.28–7.23 (m, 1H), 7.24–7.18 (m, 1H), 7.17–7.10 (m,
2H), 6.18–6.10 (m, 1H), 3.78 (t, J = 5.6 Hz, 2H), 2.43–2.29 (m, 2H),
2.16–2.08 (m, 2H), 1.58 (s, 1H), 1.51–1.41 (m, 2H), 1.40–1.31 (m, 2H),
In summary, the TA-Py-Au(III) catalysed rearrangement
of propargyl vinyl ethers was developed to synthesise allenes
in moderate to good yields. It was found there was effective
activation of the alkyne without affecting the reactivity of the
allene ester intermediates and the desired 3,3-rearrangement
products were obtained in good yields. This provides an
alternative methodology for synthesis of allene derivatives.11,13
1

JOURNAL OF CHEMICAL RESEARCH 2016 647
References
0.90 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 202.3, 137.6,
134.6, 129.8, 126.7, 126.3, 124.6, 106.4, 95.1, 60.9, 35.8, 32.6, 29.7,
22.4, 13.9.
1
2
T. Nakata, Chem. Rev., 2005, 105, 4314.
A. Grandane, M. Tanc, R. Zalubovskis and C.T. Supuran, Bioorg. Med.
Chem. Lett., 2014, 22, 1522.
3-[2-(p-Tolyl)vinylidene]heptan-1-ol (5f)13: 1H NMR (400 MHz,
CDCl3): δ 7.19 (d, J = 7.6 Hz, 2H), 7.12 (d, J = 7.6 Hz, 2H), 6.22–6.15
(m, 1H), 3.78 (t, J = 6.0 Hz, 2H), 2.39–2.30 (m, 5H), 2.16–2.07 (m,
2H), 1.73 (d, J = 12.8 Hz, 1H), 1.54–1.43 (m, 2H), 1.42–1.33 (m, 2H),
0.90 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 201.5, 136.5,
132.4, 129.4, 126.3, 105.7, 96.0, 61.0, 36.0, 32.8, 30.0, 22.5, 21.2, 13.9.
3-[2-(2-Methoxyphenyl)vinylidene]heptan-1-ol (5g)13: 1H NMR
(400 MHz, CDCl3): δ 7.33 (dd, J = 7.2, 1.2 Hz, 1H), 7.21–7.13 (m, 1H),
6.97–6.82 (m, 2H), 6.60–6.51 (m, 1H), 3.85 (s, 3H), 3.78 (s, 2H), 2.34
(td, J = 6.0, 2.8 Hz, 2H), 2.14–2.06 (m, 2H), 2.02 (s, 1H), 1.53–1.43 (m,
2H), 1.42–1.31 (m, 2H), 0.90 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz,
CDCl3): δ 202.4, 156.1, 127.8, 127.6, 123.7, 120.9, 111.1, 104.3, 90.3,
60.8, 55.6, 36.0, 32.8, 29.8, 22.5, 13.9.
3
4
A. Grandane, M. Tanc, R. Zalubovskis and C.T. Supuran, Bioorg. Med.
Chem. Lett., 2014, 24, 1256.
K. Tars, D. Vullo, A. Kazaks, J. Leitans, A. Lends, A. Grandane, R.
Zalubovskis, A. Scozzafava and C.T. Supuran, J. Med. Chem., 2013, 56,
293.
5
6
P. Leeson and B. Springthorpe, Nat. Rev. Drug Discovery, 2007, 6, 881.
D. Wang, R. Cai, S. Sharma, J. Jirak, S.K. Thummanapelli, N.G.
Akhmedov, H. Zhang, X. Liu, J. Petersen and X. Shi, J. Am. Chem. Soc.,
2012, 134, 9012.
7
8
9
D. Tejedor, G. Méndez-Abt, L. Cotosa and F. García-Tellado, Chem. Soc.
Rev., 2013, 42, 458.
N. Nella, E. Parker, J. Hitce, P. Larini, R. Jazzar and O. Baudoin, Chem.
Eur. J., 2014, 20, 13272.
B.D. Sherry and F.D. Toste, J. Am. Chem. Soc., 2004, 126, 15978.
10 B.D. Sherry, L. Maus, B.N. Laforteza and F.D. Toste, J. Am. Chem. Soc.,
2006, 128, 8132.
11 P. Mauleon, J.L. Krinsky and F.D. Toste, J. Am. Chem. Soc., 2009, 1131,
4513.
12 P. Nun, S. Gaillard, A.M.Z. Slawin and S.P. Nolan, Chem. Commun., 2010,
46, 9113.
13 D. Wang, L.N.S. Gautam, C. Bollinger, A. Harris, M. Li and X. Shi, Org.
Lett., 2011, 13, 2618.
14 D. Wang, Y. Zhang, R. Cai and X. Shi, Beilstein J. Org. Chem., 2011, 7,
1014.
15 D. Wang, Y. Zhang, A. Harris, L.N.S. Gautam, Y. Chen and X. Shi, Adv.
Synth. Catal., 2011, 353, 2584.
16 H. Peng, N.G. Akhmedov, Y. Liang, N. Jiao and X. Shi, J. Am. Chem. Soc.,
2015, 137, 8912.
17 R. Cai, M. Lu, E.Y. Aguilera, Y. Xi, N.G. Akhmedov, J.L. Petersen, H.
Chen and X. Shi, Angew. Chem. Int. Ed., 2015, 54, 8772.
18 C. Qin, Y. Su, T. Shen, X. Shi and N. Jiao, Angew. Chem. Int. Ed., 2016,
55, 350.
3-[2-(2-Chlorophenyl)vinylidene]heptan-1-ol (5h)13: 1H NMR (400
MHz, CDCl3): δ 7.78–7.25 (m, 1H), 7.24–7.18 (m, 1H), 7.17–7.11 (m,
2H), 6.18–6.10 (m, 1H), 3.78 (t, J = 5.6 Hz, 2H), 2.43–2.29 (m, 2H),
2.16–2.08 (m, 2H), 1.58 (s, 1H), 1.51–1.41 (m, 2H), 1.41–1.31 (m, 2H),
0.90 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 202.3, 137.6,
134.6, 129.8, 126.7, 126.3, 124.6, 106.4, 95.1, 60.9, 35.8, 32.6, 29.7,
22.4, 13.9.
3-[2-(2-Methoxyphenyl)vinylidene]heptan-1-ol (5i)11: 1H NMR (400
MHz, CDCl3): δ 7.24–7.18 (m, 2H), 6.88–6.81 (m, 2H), 6.21–6.13 (m,
1H), 3.82–3.74 (m, 5H), 2.43–2.25 (m, 2H), 2.15–2.05 (m, 2H), 1.73 (s,
1H), 1.52–1.29 (m, 4H), 0.90 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz,
CDCl3): δ 201.1, 158.7, 127.7, 127.5, 114.2, 105.7, 95.6, 61.0, 55.3, 36.0,
32.9, 29.8, 22.5, 13.9.
Acknowledgements
19 S.E. Motika, Q. Wang, X. Ye and X. Shi, Org. Lett., 2015, 17, 290.
20 S. Hosseyni, S. Ding, Y. Su, N.G. Akhmedov and X. Shi, Chem. Commun.,
2016, 52, 296.
21 S.K. Thummanapelli, S. Hosseyni, Y. Su, N.G. Akhmedov and X. Shi,
Chem. Commun., 2016, 52, 7687.
22 A. Gille, J. Rehbein and M. Hiersemann, Org. Lett., 2011, 13, 2122.
23 S. Jin, C. Jiang, X. Peng, C. Shan, S. Cui, Y. Niu, Y. Liu, Y. Lan, Y. Liu and
M. Cheng, Org. Lett., 2016, 18, 680.
We gratefully acknowledge financial support of this work by
the National Natural Science Foundation of China (21401080,
51302109), the Natural Science Foundation of Jiangsu Province
of China (BK20130125), Jiangsu Talents Project (2013-JNHB-
027), China Postdoctoral Science Foundation (2014M550262,
2015T80495) and MOE & SAFEA for the 111 Project (B13025).
24 Y. Liu, S. Jin, Y. Wang, S. Cui, X. Peng, Y. Niu, C. Du and M. Cheng,
Chem. Commun., 2016, 52, 6233.
25 Y. Yang, W. Hu, X. Ye, D. Wang and X. Shi, Adv. Synth. Catal., 2016, 358,
2583.
Received 9 August 2016; accepted 14 August 2016
Paper 1604207 doi: 10.3184/174751916X14754985053189
Published online: 24 October 2016