Ru(III)-catalyzed oxidation of homopropargyl alcohols in ionic liquid: an efficient and green route to 1,2-allenic ketones

Article abstract of DOI:10.1016/j.tetlet.2010.02.053

An efficient and environmentally benign synthesis of 1,2-allenic ketones via RuCl₃-catalyzed oxidation of homopropargyl alcohols in ionic liquid with tert-butyl hydroperoxide (TBHP) as the oxidant was reported for the first time. With its reasonable efficiency and green nature, this oxidation provides a novel alternative route to 1,2-allenic ketones.

Full text of DOI:10.1016/j.tetlet.2010.02.053

Tetrahedron Letters 51 (2010) 2123–2126
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Tetrahedron Letters
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Ru(III)-catalyzed oxidation of homopropargyl alcohols in ionic liquid: an
efficient and green route to 1,2-allenic ketones
*
Xuesen Fan , Yingying Qu, Yangyang Wang, Xinying Zhang, Jianji Wang
School of Chemistry and Environmental Sciences, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Xinxiang, Henan 453007, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and environmentally benign synthesis of 1,2-allenic ketones via RuCl3-catalyzed oxidation of
homopropargyl alcohols in ionic liquid with tert-butyl hydroperoxide (TBHP) as the oxidant was reported
for the first time. With its reasonable efficiency and green nature, this oxidation provides a novel alter-
native route to 1,2-allenic ketones.
Received 7 November 2009
Revised 8 February 2010
Accepted 10 February 2010
Available online 13 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Allenic ketones have shown interesting reactivity1,2 by acting as
Michael acceptors,3 Diels–Alder dienophiles,2 building blocks in
furan,4 and 1,3-dipoles in unusual [8+2] annulation.5 Due to their
importance, various synthetic routes to allenic ketones have been
reported.6–8 In particular, one often used approach involves the
reaction of allenyl or homopropargylmetals with carbonyl com-
pounds, followed by oxidation of the resulting allenic or homo-
propargylic alcohols.9 The oxidant used in the above-mentioned
method is usually DMP (Dess–Martin Periodinane) and the reac-
tion is called Dess–Martin oxidation. Though Dess–Martin oxida-
tion is an efficient procedure, the formation of the corresponding
1,2-allenic ketones is in many cases along with side products
resulting from either the addition of acetic acid (from DMP) to
the allenes with electron-rich substituents or the isomerization
of the 1,2-allenic ketones with electron-withdrawing substitu-
ents.10 Moreover, Dess–Martin oxidation and other traditional
methods usually involve the use of stoichiometric or excessive me-
tal reagents, toxic organic solvents, or require harsh reaction con-
ditions. Therefore, the development of methods with less
environmentally adverse impact still remains a challenge.
On the other hand, transition metal-catalyzed reactions are
among the most powerful tools in modern organic synthesis. In
this regard, organic transformations catalyzed by ruthenium(III)
species have been a focus of attention in the recent years due to
their high efficiency and excellent chemoselectivity. The use of cat-
alytic amount of ruthenium(III) together with oxidants such as
H2O2,11 CH3CO3H,12 NaIO4,13 oxygen,14 (diacetoxyiodo)benzene
(DIB),15 bromamine-T,16 CeCl3/NaIO4,17 and oxygen/sodium cya-
nide,18 have been used in an array of oxidative transformations,
such as oxidation of phenols, alcohols, and unactivated C–H bond;
oxidative cleavage of olefins to aldehydes; oxidation of Hantzsch
1,4-dihydropyridine to the corresponding pyridines, and dihydr-
oxylation of unreactive olefins and oxidative cyanation of tertiary
amines.
In a recent research program, we needed some 1,2-allenic ke-
tones for the preparation of substituted furans. Considering that
RuCl3 as well as other ruthenium salts and complexes has been
successfully used to catalyze the oxidation of a number of sub-
strates with various stoichiometric oxidants as mentioned previ-
ously, we envisioned a new route to 1,2-allenic ketone through
RuCl3-catalyzed oxidation of homopropargyl alcohols19 by using
tert-butyl hydroperoxide (TBHP) or hydrogen peroxide (H2O2) as
the oxidant. Herein, we report that RuCl3/TBHP is able to transform
a variety of homopropargyl alcohols to 1,2-allenic ketones with a
reasonable efficiency.
The study was initiated by using 1-(4-bromophenyl)but-3-yn-
1-ol (1a, Scheme 1) as the substrate and the reaction was firstly
run in CH2Cl2. It turned out that when 1a was treated with RuCl3
(0.01 equiv) and TBHP (3 equiv) at rt, 2a could be obtained, but
in low yield (Table 1, entry 1). With higher amount of RuCl3 and
higher reaction temperature, the yields of 2a increased remarkably
(entries 2–6). With 0.04 equiv of RuCl3 and 4 equiv of TBHP, 2a
could be obtained in a yield of 80% after the reaction mixture being
stirred under reflux for 2 h (entry 6). The oxidation was also stud-
ied in other solvents such as CH3CN and THF, but the yields of 2a
were lower than that in CH2Cl2 (entries 8 and 9). Remarkably, this
reaction could be carried out efficiently in two readily available
OH
O
catalyst/oxidant
solvent
Br
Br
1a
2a
* Corresponding author. Tel.: +86 373 332 9261; fax: +86 373 332 6336.
E-mail addresses: xuesen.fan@henannu.edu.cn, fanxs88@263.net (X. Fan).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.053

2124
X. Fan et al. / Tetrahedron Letters 51 (2010) 2123–2126
Table 1
Oxidation of homopropargyl alcohol (1a) under different reaction conditionsa
Entry
Solvent
Amount of RuCl3 (equiv)
Amount of TBHP (equiv)
Amount of H2O2 (equiv)
Reaction time (h)
Temperature (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
0.01
0.02
0.03
0.04
0.03
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
3
3
3
3
3
4
5
4
4
3
3
4
5
4
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
5
5
5
5
2
2
2
2
2
3
4
4
4
4
4
4
rt
rt
rt
rt
Reflux
Reflux
Reflux
Reflux
Reflux
80
80
80
80
80
80
80
25
33
40
51
73
80
81
65
55
60
70
75
74
22
25
20
THF
[bmim]BF4
[bmim]PF6
[bmim]PF6
[bmim]PF6
H2O
[bmim]PF6
H2O
5
a
Reaction conditions: 1a (1 mmol).
Isolated yields.
b
(entry 12). Though the yield was lower than that with CH2Cl2, we
prefer [bmim]PF6 as the oxidation medium due to the fact that
those 1-alkyl-3-methylimidazolium-based ionic liquids have
emerged as promising alternative green solvents for chemical syn-
thesis because of their negligible vapor pressure, easy recyclability,
and reusability.20 The reaction was also tried in H2O, but the yield
was unfortunately low (entry 14). In addition, when H2O2 was used
as an oxidant, 2a was obtained in much lower yields compared
with that of TBHP (entries 15 and 16).
OH
O
RuCl3/TBHP
R1
R
R
[bmim]PF6, 80oC
R1
2
1
Scheme 2.
ionic liquids, [bmim]BF4 and [bmim]PF6 (entries 10–13). It turned
out that 2a was obtained in a yield of 75% with 0.04 equiv of RuCl3
and 4 equiv of TBHP by treating the mixture in [bmim]PF6 at 80 °C
With the optimized reaction conditions, the oxidation of a range
of substrates was then investigated (Scheme 2) and the examples
Table 2
a
Oxidation of homopropargyl alcohols with RuCl3/TBHP in [bmim]PF6
Entry
Homopropargyl alcohol
Product
Reaction time (h)
Yieldb (%)
OH
O
1
4
75
Br
1a
1b
Br
2a
2b
OH
O
2
3
4
4
73
72
Cl
Cl
OH
O
F
1c
F
2c
OH
O
4
5
6
4
4
4
73
76
70
H3C
H3C
1d
2d
OH
O
2e
1e
OH
O
Br
Br
1f
2f

X. Fan et al. / Tetrahedron Letters 51 (2010) 2123–2126
2125
Table 2 (continued)
Entry
Homopropargyl alcohol
Product
Reaction time (h)
4
Yieldb (%)
OH
O
H3C
H3C
7
8
72
70
1g
2g
OH
O
F
F
4
6
1h
2h
OH
O
9
55
Cl
Cl
1i
2i
OH
O
10
11
6
8
58
F
F
2j
1j
O
21c
OH
OH
1k
2k
CH3
O
CH3
12
13
4
4
72
70
H3C
H3C
Br
2l
1l
CH3
O
OH
CH3
Br
2m
1m
CH3
OH
O
Br
CH3
14
5
66
2n
Br
1n
a
Reaction conditions: 1 (1 mmol), RuCl3 (0.04 mmol), TBHP (4 mmol), [bmim]PF6 (1 mL), 80 °C.
Isolated yields.
H NMR yield.
b
c
are summarized in Table 2. It was observed that with aryl-substi-
with certain amount of TBHP. 21The results shown in Table 3 dem-
onstrate that it was readily recyclable for at least three times, with
only slight drop in its catalytic activity over each cycle.
tuted homopropargyl alcohols (Table 2, entries 1–10), the reactions
underwent smoothly, and the corresponding products were pro-
duced in moderate yields. With either electron-withdrawing or
electron-donating groups at the para position of the phenyl ring,
the oxidation proceeded efficiently (Table 2, entries 1–4). The reac-
tions were slowed with substrates bearing substituted groups at
the ortho position of the phenyl ring (Table 2, entries 9 and 10).
These results indicated that the electronic effect on the phenyl ring
in these propargyl alcohols did not play a significant role in affect-
ing the oxidation, probably due to their high reactivity. In contrast,
steric hindrance seemed to be an important factor in affecting the
oxidation. Moreover, various functional groups such as alkyl and
halide on the phenyl ring were well tolerated under these condi-
tions. It is worth to be noted that the oxidation of aliphatic sub-
strate was much more difficult and the corresponding product
was only formed in low yield (Table 2, entry 11). Encouragingly,
with internal alkyne substrates (1l, 1m, and 1n), the reaction
underwent smoothly to afford the corresponding 1,2-allenic ke-
tones in moderate yields (Table 2, entries 12–14).21
In conclusion, a novel and green method for the preparation of
1,2-allenic ketones through the oxidization of propargyl alcohols
with RuCl3 as a catalyst and TBHP as an oxidant was developed.
This oxidation proceeds under mild conditions and a series of func-
tional groups can be tolerated. Due to its environmentally benign
nature and reasonable efficiency, this method provides a novel
alternative to 1,2-allenic ketones and may stimulate further re-
search efforts on reactions catalyzed by RuCl3 species in ionic liq-
uids. Studies to probe the mechanism and to broaden the scope
of these reactions are currently underway in our laboratory and
the results will be reported in due course.
Table 3
Reusability study of the catalytic system in the preparation of 2a
Run
Temperature (°C)
Time (h)
Yielda (%)
1
2
3
4
80
80
80
80
4
4
4
5
75
71
68
61
Next, the recyclability of the oxidation system was studied by
using 1a as the model substrate. It followed that RuCl3 together
with [bmim]PF6 could be reused for a new cycle after being fully
extracted with diethyl ether (10 mL Â 3), dried in vacuo and added
a
Isolated yield.

2126
X. Fan et al. / Tetrahedron Letters 51 (2010) 2123–2126
21. General procedure for the preparation of 1,2-allenic ketones: To 1 mL of
[bmim]PF6 in round-bottomed flask were added propargyl alcohol
Acknowledgments
a
(1 mmol) and RuCl3 (0.04 mmol) at rt. The flask was then put into an oil
bath. Over rigorous stirring, TBHP (4 mmol) was added dropwise, during which
time, the oil bath was gradually heated to 80 °C. Upon completion of addition,
the mixture was stirred at 80 °C and the reaction was monitored by TLC. Upon
completion, H2O (5 mL) was added and the mixture was extracted with diethyl
ether (10 mL Â 3). The combined organic phases were washed with H2O and
dried over MgSO4, filtered, and concentrated under vacuum. The crude product
was purified by column chromatography eluting with hexane/ethyl acetate (0–
5%) to give the corresponding 1,2-allenic ketone products. The ionic liquid
phase was concentrated and dried in vacuo overnight for reuse. 2a: liquid; IR
This work was financially supported by the National Natural
Science Foundation of China (Nos. 20772025 and 20972042), Pro-
gram for Science & Technology Innovation Talents in Universities
of Henan Province (No. 2008HASTIT006) and the Natural Science
Foundation of Henan Province (Nos. 092300410192 and
094300510054).
(neat): 2930, 2858, 1960, 1935, 1670 cmÀ1 1H NMR (400 MHz, CDCl3) d: 5.27
;
References and notes
(d, 2H, J = 6.4 Hz, CH2), 6.39 (t, 1H, J = 6.4 Hz, CH), 7.59 (d, 2H, J = 8.4 Hz, ArH),
7.76 (d, 2H, J = 8.4 Hz, ArH). 13C NMR (100 MHz, CDCl3) d: 79.5, 93.2, 127.9,
130.2, 131.7, 136.1, 190.0, 217.2. MS: m/z 245 [M+Na]+. HRMS (FAB) Calcd for
C10H8BrO: 222.9758 (MH)+, found: 222.9755. Compound 2b: liquid; IR (neat):
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2931, 2858, 1961, 1938, 1668 cmÀ1 1H NMR (400 MHz, CDCl3) d: 5.27 (d, 2H,
;
J = 6.4 Hz, CH2), 6.39 (t, 1H, J = 6.4 Hz, CH), 7.42 (d, 2H, J = 8.4 Hz, ArH), 7.84 (d,
2H, J = 8.4 Hz, ArH). 13C NMR (100 MHz, CDCl3) d: 79.5, 93.2, 128.7, 130.1,
135.7, 139.2, 189.8, 217.2. MS: m/z 201 [M+Na]+. HRMS (FAB) Calcd for
C10H8ClO: 179.0263 (MH)+, found: 179.0263. Compound 2d: liquid; IR (neat):
2925, 2860, 1961, 1932, 1670 cmÀ1 1H NMR (400 MHz, CDCl3) d: 2.41 (s, 3H,
;
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J = 8.0 Hz, ArH), 7.82 (d, 2H, J = 8.0 Hz, ArH). 13C NMR (100 MHz, CDCl3) d: 21.6,
79.1, 93.1, 128.8, 129.1, 134.9, 143.7, 190.5, 216.8. MS: m/z 181 [M+Na]+. HRMS
(FAB) Calcd for C11H11O: 159.081 (MH)+, found: 159.0819. Compound 2e:
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liquid; IR (neat): 2926, 2856, 1961, 1932, 1670 cmÀ1 1H NMR (400 MHz,
;
CDCl3) d: 5.27 (d, 2H, J = 6.4 Hz, CH2), 6.46 (t, 1H, J = 6.4 Hz, CH), 7.44–7.48 (m,
2H, ArH), 7.55–7.59 (m, 1H, ArH), 7.90–7.92 (m, 2H, ArH). 13C NMR (100 MHz,
CDCl3) d: 79.2, 93.2, 128.3, 128.7, 132.8, 137.4, 191.0, 217.1. MS: m/z 167
[M+Na]+. HRMS (FAB) Calcd for C10H9O: 145.0653 (MH)+, found: 145.0658.
Compound 2g: liquid; IR (neat): 2922, 2864, 1960, 1934, 1665 cmÀ1 1H NMR
;
(400 MHz, CDCl3) d: 2.42 (s, 3H, CH3), 5.26 (d, 2H, J = 6.4 Hz, CH2), 6.46 (t, 1H,
J = 6.4 Hz, CH), 7.34–7.39 (m, 2H, ArH), 7.70–7.72 (m, 2H, ArH). 13C NMR
(100 MHz, CDCl3) d: 21.3, 79.2, 93.2, 125.9, 128.2, 129.1, 133.6, 137.4, 138.2,
191.1, 217.0. MS: m/z 181 [M+Na]+. HRMS (FAB) Calcd for C11H11O: 159.081
(MH)+, found: 159.0815. Compound 2m: liquid; IR (neat): 2928, 1960, 1934,
1651 cmÀ1 1H NMR (400 MHz, CDCl3) d: 1.99–2.02 (m, 3H, CH3), 5.04–5.07 (m,
;
2H, 2 Â CH), 7.53 (d, 2H, ArH, J = 8.4 Hz), 7.63 (d, 2H, ArH, J = 8.4 Hz). 13C NMR
(100 MHz, CDCl3) d: 14.6, 78.7, 102.0, 126.7, 130.5, 131.1, 136.8, 193.9, 217.5.
MS: m/z 259 [M+Na]+. HRMS (FAB) Calcd for C11H10BrO: 236.9915 (MH)+,
found: 236.9909. Compound 2n: liquid; IR (neat): 2927, 2864, 1934,
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;
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(m, 1H, ArH). 13C NMR (100 MHz, CDCl3) d: 14.5, 78.9, 102.1, 121.9, 127.5,
129.4, 131.9, 134.7, 139.8, 193.8, 217.8. MS: m/z 259 [M+Na]+. HRMS (FAB)
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