Synthesis of 1,2-allenic ketones through oxidation of homopropargyl alcohols with CrO3(cat.)/TBHP under MWI

Article abstract of DOI:10.1016/j.cclet.2010.09.032

A CrO₃ catalyzed oxidation of homopropargyl alcohols with tert-butyl hydroperoxide under microwave irradiation was found to be an efficient and rapid alternative for the preparation of 1,2-allenic ketones. The advantages of this procedure inclu

Full text of DOI:10.1016/j.cclet.2010.09.032

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 268–271
www.elsevier.com/locate/cclet
Synthesis of 1,2-allenic ketones through oxidation of
homopropargyl alcohols with CrO3(cat.)/TBHP under MWI
*
Xin Ying Zhang , Ying Ying Qu, Yang Yang Wang, Xue Sen Fan
*
School of Chemistry and Environmental Science, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University,
Xinxiang 453007, China
Received 7 June 2010
Available online 22 December 2010
Abstract
A CrO3 catalyzed oxidation of homopropargyl alcohols with tert-butyl hydroperoxide under microwave irradiation was found to
be an efficient and rapid alternative for the preparation of 1,2-allenic ketones. The advantages of this procedure include short
reaction time, less adverse impact on the environment and reasonably high efficiency.
# 2010 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
Keywords: Allenic ketones; Oxidation; Microwave irradiation; Chromium(VI) oxide; tert-Butyl hydroperoxide
Oxidation is among the most used transformations in organic chemistry and is frequently accomplished by the use
of chromium reagents since they are efficient, cheap and readily available. However, many oxidation processes
involved chromium agents in quantities ranging from stoichiometric to a large excess, which are unfortunately not
compatible with environmental regulations since chromium residues are environmentally hazardous. Therefore, it
would be advantageous to develop oxidizing methods requiring only catalytic amounts of Cr(VI) while still exploiting
its excellent oxidative capability [1,2]. In the meantime, the utility of microwave energy in synthetic organic chemistry
has been increasingly recognized due to the fact that compared with conventional heating, reactions promoted by
microwave irradiation (MWI) have shown enhanced reaction rate, greater selectivity and thus an environmentally
friendly nature.
1,2-Allenic ketones are an important class of compounds with numerous applications in organic synthesis [3–7].
Due to their importance, various synthetic routes to 1,2-allenic ketones have been reported [8–10]. In particular, one
often used protocol involves firstly the reaction of allenylmetals with carbonyl compounds, followed by oxidation of
the resulting allenic or homopropargylic alcohols [11]. The oxidant used is usually DMP (Dess–Martin Periodinane).
Though Dess–Martin oxidation is an efficient procedure, the formation of 1,2-allenic ketones usually needs extended
reaction period and is often contaminated by side products [12]. Therefore, the development of rapid and more
efficient procedures for the preparation of 1,2-allenic ketones still remains a challenge.
* Corresponding authors.
E-mail addresses: xinyingzhang@henannu.edu.cn (X.Y. Zhang), xuesen.fan@henannu.edu.cn (X.S. Fan).
1001-8417/$ – see front matter # 2010 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
doi:10.1016/j.cclet.2010.09.032

[()TD$FIG]
X.Y. Zhang et al. / Chinese Chemical Letters 22 (2011) 268–271
OH
269
O
Various conditions
1a
2a
Scheme 1.
As part of our ongoing research efforts towards the development of synthetic methodologies for the preparation of
important organic compounds, we envisioned a new route to 1,2-allenic ketone through the oxidation of
homopropargyl alcohols under MWI with catalytic CrO3 together with an environmentally benign oxidant.
Initially, 1-phenylbut-3-yn-1-ol (1a, Scheme 1), prepared from benzaldehyde and propargyl bromide in the
presence of zinc [13], was used as a model substrate to study the effects of various reaction conditions and different
oxidants on this reaction. The results were summarized in Table 1.
Table 1
Optimization of the reaction conditions for the synthesis of 2aa.
Entry
Solvent
CrO3 (equiv.)
Oxidant
Time (h)
Temp. (8C)
Yield (%)e
1
2
H2Ob
0.03
0.03
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
H2O2
5
rt
Trace
Trace
21
H2Ob
H2O2
5
60
3
H2Ob
H2Ob
H2O2
5
80
4
H2O2
0.5
5
MWI
rt
30
b
b
b
b
b
b
5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
TBHP
TBHP
TBHP
TBHP
TBHP
TBHPd
TBHP
TBHP
TBHP
TBHP
25
6
3
reflux
MWI
MWI
MWI
MWI
MWI
MWI
MWI
MWI
41
7
0.2
0.5
0.8
0.5
0.5
0.5
0.5
0.5
62
8
63
9
60
10
11
12
13
14
55
CH3CNb
THFb
42
36
c
[bmim]BF4
41
c
[bmim]PF6
46
a
Reaction conditions: 1 mmol of 1a and 3 equiv. of oxidant were used.
10 mL of solvent were used.
b
c
d
e
1 mL of solvent were used.
2 equiv. of oxidant were used.
Isolated yields.
Table 2
Synthesis of 1,2-allenic ketones with CrO3/TBHP under MWIa.
1
R
Entry
R
Product
Time (min)
Yield (%)b
1
2
C6H5
H
2a
2b
2c
2d
2e
2f
12
12
10
10
13
10
13
10
15
30
10
10
62
65
70
71
69
62
55
50
48
18c
61
62
p-CH3C6H4
p-ClC6H4
p-BrC6H4
p-FC6H4
H
3
H
4
H
5
H
6
m-CH3C6H4
m-BrC6H4
m-FC6H4
o-ClC6H4
C6H5CH2
p-BrC6H4
p-CH3C6H4
H
7
H
2g
2h
2i
8
H
9
H
10
11
12
H
2j
Me
Me
2k
2l
a
Reaction conditions: 1 (1 mmol), CrO3 (0.05 equiv.), TBHP (3 equiv.), MWI, 40 8C.
Isolated yields.
b
c
NMR yield.

2[()TD$FIG] 70
X.Y. Zhang et al. / Chinese Chemical Letters 22 (2011) 268–271
R1
OH
O
CrO3/TBHP
R1
R
R
CH2Cl2, MWI
1
2
Scheme 2.
In the first place, aqueous H2O2 was chosen as the oxidant. It turned out that with conventional heating, the reaction
underwent slowly and the yields of 2a were low (Table 1, entries 1–3). When MWI was introduced, the time period for
a complete conversion shortened, but the yield was still unsatisfactory (entry 4). We then resorted to another kind of
peroxide, tert-butyl hydroperoxide (TBHP), to replace H2O2. Encouragingly, the reactions with TBHP improved
significantly compared with that of H2O2 (entries 5–7). Various organic solvents were also tried as the reaction
medium and CH2Cl2 gave the best results (entries 5–12). In CH2Cl2, the reaction period for a complete consumption of
the starting material at room temperature or under conventional heating was 5 h or 3 h, respectively (entries 5–6).
Under MWI, however, the reaction time was strikingly shortened to 12 min, reflecting the specific non-thermal effects
under MWI conditions (entry 7). On the other hand, it has been reported that ionic liquids (ILs) are excellent
microwave absorbing agents due to their thermal stability, high ionic conductivity and polarizability [14], it was then
of our interests to explore MWI technique in two readily available ILs, [bmim][BF4] and [bmim][PF6]. However, it
turned out the reactions carried out in ILs did not give improved results compared with that with other conventional
organic solvents (entries 13–14). Therefore, the optimal conditions were obtained as: the solution of 1a in CH2Cl2 was
irradiated with MW at 40 8C for 0.2 h in the presence of 5 mol% of CrO3 as catalyst and 3 equiv. of TBHP as oxidant
(entry 7).
With the optimized reaction conditions, the scope and limitations of this oxidation was evaluated. It was observed
that, with aryl substituted homopropargyl alcohols, the reactions underwent smoothly and the corresponding products
were obtained in moderate yields [15]. With either electron-withdrawing or electron-donating groups at the para
position of the phenyl rings, the oxidative reactions were equally efficient (entries 2–5, Table 2). The reactions were
slowed with substrate bearing substituent at the ortho position (entry 9, Table 2). These results indicated that the
electronic effect on the phenyl group did not play a significant role in affecting the oxidation, probably due to their high
reactivity. In contrast, steric hindrance seems to be a key factor in affecting the oxidation of these substrates. Moreover,
various functional groups, such as alkyl and halide groups on phenyl rings, were well tolerated under these conditions.
It is worth to be noted that the oxidation of aliphatic substrate was complicated and the corresponding product was only
formed in low yield (entry 10, Table 2). On the other hand, with internal alkyne substrates, the reactions underwent
smoothly and afforded the corresponding 1,2-allenic ketones with good yields (entries 11–12, Table 2) (Scheme 2).
In conclusion, we have introduced an efficient and rapid procedure for the preparation of 1,2-allenic ketone through
oxidation of propargyl alcohols with TBHP catalyzed by CrO3 in CH2Cl2 under MWI. To the best of our knowledge,
this is the first report of synthesis of 1,2-allenic ketone with catalytic Cr(VI) species under MWI and these new reaction
conditions open an important alternative to the use of large amount of toxic reagents and long time conventional
heating. Further studies to probe the mechanism of this transformation and to broaden the scope of these reactions are
currently underway in our laboratory and will be reported in due course.
Acknowledgments
We are grateful to the National Natural Science Foundation of China (Nos. 20772025 and 20972042), Innovation
Scientists and Technicians Troop Construction Projects of Henan Province (No. 104100510019), Natural Science
Foundation of Henan Province (No. 092300410237) and the Natural Science Foundation of Department of Education
of Henan Province (Nos. 2009A150017 and 2008A150013).
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[15] General procedure for the oxidation of homopropargyl alcohols to 1,2-allenic ketones. To a solution containing propargyl alcohol (1 mmol) and
CrO3 (0.05 mmol) in CH2Cl2 (10 mL) was added TBHP (3 mmol) at room temperature. The mixture was then put into a commercially available
single-mode microwave synthesis apparatus equipped with a high sensitivity infrared sensor for temperature control and measurement (MAS-I,
Sineo Microwave Chemical Technology Co. Ltd., Shanghai, P.R. China) and irradiated at 300 W (internal temperature 40 8C) for the time
period listed in Table 2. Upon completion, the mixture was filtered over Celite. The solvent was evaporated under reduced pressure and the
residue was subjected to flash chromatography (eluted with petroleum ether/ethyl acetate) to afford the corresponding 1,2-allenic ketone
product. 2a: 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. 2c: liquid; IR
(neat): 2920, 2868, 1960, 1932, 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. 2k: liquid; IR (neat): 2928, 1960, 1934, 1651 cmÀ1
;
1H NMR (400 MHz, CDCl3): d 1.99–2.01 (m, 3H, CH3), 5.04–5.06 (m, 2H, 2Â 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)
1
Calcd. for C11H10BrO: 236.9915 (MH)+, found: 236.9909. 2l: liquid; IR (neat): 2923, 2870, 1960, 1934, 1665 cmÀ1; H NMR (400 MHz,
CDCl3): d 1.99–2.02 (m, 3H, CH3), 2.40 (s, 3H, CH3), 5.02–5.04 (m, 2H, 2Â CH), 7.20 (d, 2H, ArH, J = 8.0 Hz), 7.70 (d, 2H, ArH, J = 8.0 Hz).
13C NMR (100 MHz, CDCl3): d 14.8, 21.6, 78.2, 101.8, 128.5, 129.5, 135.3, 142.6, 194.7, 217.2. MS: m/z 195 [M+Na]+. HRMS (FAB) Calcd.
for C12H13O: 173.0966 (MH)+, found: 173.0966.