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A. Nait Ajjou, G. Ferguson / Tetrahedron Letters 47 (2006) 3719–3722
low yields were obtained.14 Muzart and Piva reported
the first Cr(VI)-catalyzed a-oxidation of alkynes with
tert-butyl hydroperoxide (TBHP), and only moderate
yields were reached although large excess of TBHP
was used and long reaction time. In addition, the oxida-
tion reactions were mostly performed in benzene.15
SeO2/TBHP system was also used for the oxidation of
propargylic methylenes.16 The internal alkynes studied
underwent a,a0-oxidation which led to a mixture of
mono- and di-oxygenated acetylenic alcohols and
ketones, with ynones as minor products.16a Recently,
Ishii and co-workers reported that alkynes were
converted by aerobic oxidation into a,b-acetylenic
ketones with good yields using N-hydroxyphthalimide
combined with a transition metal.17
Table 1. Oxidation of 1-phenyl-1-butyne (1) catalyzed by
CuCl2Æ2H2O/BQCa
Entry TBHP Conversion
(equiv) (%)
Yield (%)
O
OOtBu
CH3
Ph
Ph
CH3
1
1
1
2
3
4
4
4
4
4
22
10
72
15
9
7
0
2b
3
55
89
98
96
62
47
36
17
Traces
0
0
Traces
21
20
4
5
6c
7d
8e
9f
92
100
100
64
70
58
a Reaction conditions: 1-phenyl-1-butyne (2 mmol), BQC (0.02 mmol),
CuCl2 (0.02 mmol), Na2CO3 (0.14 mmol), TBAC (0.06 mmol),
TBHP (2–8 mmol), water (5 mL), rt, 24 h.
b The reaction is performed without TBAC.
c Second cycle of entry 5.
Aerobic oxidations of alkynes were also performed
using hydroperoxides and metallic catalysts.18,19 Non-
heme iron complexes combined to hydrogen peroxide
or TBHP led to poor yields and selectivities for a,b-acet-
ylenic ketones,18 while better results were obtained with
Cu2+/TBHP system.19 Finally, iron phthalocyanines
grafted onto silica were successfully used as catalysts
for the oxidation of alkynes to ynones with excess
TBHP.20 We recently reported different transformations
in water.21 Despite the evident ecological and economi-
cal advantages of aqueous phase catalysis, to the best of
our knowledge there are no reports concerning selective
a-oxidation of alkynes to a,b-acetylenic ketones in
water. In this letter, we are pleased to disclose an
unprecedented highly efficient oxidation of alkynes to
the corresponding ynones in water with aqueous tert-
butyl hydroperoxide catalyzed by the system composed
of CuCl2 and BQC (2,20-biquinoline-4,40-dicarboxylic
acid dipotassium salt).
d Third cycle of entry 5.
e Fourth cycle of entry 5.
f Fifth cycle of entry 5.
phase catalysis is the possibility to separate and recycle
the catalyst, we investigated the durability of CuCl2/
BQC system by carrying out five consecutive cycles with
the same catalyst aqueous phase separated from the
organic phases. A fresh charge of 1 (2 mmol), TBHP
(8 mmol), and TBAC (0.06 mmol) was used in each
cycle. The results summarized in Table 1 show that after
the second cycle the conversions decreased and mixtures
of 2 and 3 were obtained (Table 1, entries 5–9).
To evaluate the synthetic potential of CuCl2/BQC sys-
tem, various aromatic and aliphatic alkynes were sub-
jected to the oxidation with 4 equiv of TBHP (Table
2).23 The oxidation of aromatic alkynes proceeded
smoothly with excellent yields and full conversions in
most cases (Table 2, entries 1–3). 1-Phenyl-1-hexyne
was oxidized with 88% conversion yielding 1-phenyl-1-
hexyn-3-one and the corresponding propargylic tert-
butylperoxy ether with 78% and 9% yields, respectively.
Increasing the reaction time to 48 h allowed the forma-
tion of the ynone with excellent yield (89%) and only 2%
of the mixed peroxide was detected (Table 2, entry 3).
Our catalytic system is also highly efficient for the oxida-
tion of internal alkynes. Transformation of 2-octyne oc-
curred regioselectively yielding 2-octyn-4-one with
excellent conversion and selectivity, while remarkably
4-octyne was fully converted to 4-octyn-3-one as a sole
product with very high selectivity (Table 2, entries 4
and 5). In the case of terminal alkynes, the oxidations
are sluggish and only yields of 32–40% were reached
(Table 2, entries 6–8). Moreover, no increase in the
yields was observed with longer reaction time.
In our preliminary experiments, we investigated the oxi-
dation of 1-phenyl-1-butyne (1), chosen as a model sub-
strate. Thus, the oxidation of 1 (2 mmol) with aqueous
tert-butyl hydroperoxide (1 equiv, 2 mmol) in the pres-
ence of CuCl2 (0.02 mmol), BQC (0.02 mmol), tetra-
butylammonium chloride (0.06 mmol), and Na2CO3
(0.14 mmol) in distilled water gave 4-phenyl-3-butyn-2-
one (2) and 3-tert-butylperoxy-1-phenyl-1-butyne (3)22
with 15% and 7% yields, respectively (Table 1, entry
1). Our first experiments showed that the presence of
CuCl2, BQC, and Na2CO3 together is required to
achieve the oxidation of 1 with TBHP. Also, no reaction
was observed when the reaction of 1 was performed with
1 equiv of hydrogen peroxide, lithium perchlorate, so-
dium percarbonate, or sodium hypochlorite, alone or
combined with TBHP (0.25 equiv). When the oxidation
of 1-phenyl-1-butyne was repeated without TBAC, con-
version of 10% was observed and product 2 was ob-
tained with 9% yield (Table 1, entry 2). As the
quantity of TBHP was increased from 2 to 4 equiv, the
amounts of a,b-acetylenic ketone increased in detriment
of propargylic tert-butylperoxy ether which decreased
markedly, and full conversion of 1 to 2 with excellent
selectivity was achieved with 4 equiv of TBHP (Table
1, entries 3–5). The reaction performed under argon
showed that the catalytic system is as efficient as under
air. Since one of the most important aspect of aqueous
The previous reports that described a-oxidation of
alkynes to a,b-acetylenic ketones suggested propargylic
alcohols as the intermediates, and no study ever
mentioned the formation of propargylic alkylperoxy
ethers.15,16a,17,19,20 To the best of our knowledge, this
is the first time that the formation of propargylic alkyl-
Nait Ajjou, Abdelaziz
