Oxidation of alkynes in aqueous media catalyzed by diphenyl diselenide

Article abstract of DOI:10.1055/s-0029-1219817

In this communication we propose a convenient methodology to effect the oxidation of alkynes using ammonium persulfate and diphenyl diselenide as catalyst. The reactions effected in aqueous media lead to 1,2-unprotected dicarbonyl derivatives or to hemiacetals starting from terminal alkynes.

Full text of DOI:10.1055/s-0029-1219817

1402
LETTER
Oxidation of Alkynes in Aqueous Media Catalyzed by Diphenyl Diselenide
O
xidation of
A
t
lkynes
e
in Aqueou
f
s
Mediaano Santoro, Benedetta Battistelli, Blerina Gjoka, Chun-wing Steven Si, Lorenzo Testaferri, Marcello Tiecco,
Claudio Santi*
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy
Fax +39(075)5855116; E-mail: santi@unipg.it
Received 4 March 2010
Particular attention has been devoted to the oxidation of
Abstract: In this communication we propose a convenient method-
ology to effect the oxidation of alkynes using ammonium persulfate
and diphenyl diselenide as catalyst. The reactions effected in aque-
ous media lead to 1,2-unprotected dicarbonyl derivatives or to
hemiacetals starting from terminal alkynes.
alkynes, whereas this procedure is frequently complicated
by the overoxidation affording the corresponding carbox-
ylic acids.11
Here we report that ammonium persulfate in aqueous con-
ditions can effect this oxidation and that diphenyl dise-
lenide catalyzes the process leading directly to the
formation of unprotected 1,2-dicarbonyl derivatives.
Key words: selenium, oxidation, catalysis, alkynes, water chemis-
try
The development of improved and eco-friendly oxidation
reactions is an area of great current interest in both aca-
demic and industrial laboratories. Recently we reported
the use of diphenyl diselenide as a precatalyst in the am-
monium persulfate as well as in the hydrogen peroxide
mediated dihydroxylation of olefins.1
O
(PhSe)2 cat.
oxidant
Ph
Ph
Me
Me
H2O–MeCN (3:1)
O
1a
2a
Scheme 1 Oxidation of 1-phenyl-1-propyne
In the first case1a the reactions proceed through an hydroxy-
selenenylation followed by substitutive deselenenylation,
whereas when using hydrogen peroxide as oxidant the
mechanism has been demonstrated to involve an epoxida-
tion promoted by the in situ formed perseleninic acid, fol-
lowed by the attack of a molecule of water.
Preliminary experiments were carried out on 1-phenyl-1-
propyne (1a) using several oxidants in the presence of a
different concentrations of catalyst (PhSe)2 and at differ-
ent temperature (Scheme 1). The results summarized in
Table 1 clearly demonstrate that H2O2 (35%), MCPBA,
and peracetic acid (30%) are not suitable oxidants for this
reaction. On the contrary ammonium persulfate at 60 °C
slowly converts 1a into the corresponding diketone 2a,
and the reaction can be accelerated by the presence of
diphenyl diselenide.
As an extension of our investigation concerning the use of
organoselenium compounds as catalysts for greener syn-
thetic procedures2 we take in consideration the oxidation
of carbon–carbon triple bond considering also the wide
availability of alkynyl substrates. Diphenyl diselenide, in
refluxing methanol in the presence of an excess of ammo-
nium persulfate, converts alkynes into the corresponding
di- or monoprotected a-dicarbonylic compounds.3 In the
same paper it has been reported an example in which a
stoichiometric amount of diphenyl diselenide produces
the unprotected derivatives when the solvent is a MeCN–
H2O mixture.
Table 1 Investigation of Reaction Conditions
Oxidant
(PhSe)2 (%)
Yield (%)
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
oxidantb
10
100
0
75a
80a
27a
–
1,2-Dicarbonyl derivatives are known to be useful and
versatile synthones.4 Recently they were successfully em-
ployed in the synthesis of the imidazole core5 present in a
series of well-known drugs. Since their value as starting
materials, many methods have been developed for the
synthesis of these compounds: ruthenium tetroxide oxida-
tion of acyloins,6 a-bromoketones,6 and carbon–carbon
multiple bonds,7 oxidative hydrolysis using silver salts of
ketodithianes,8 coupling reaction of acetic anhydride with
aldehydes assisted by CoCl2,9 and oxidation of vic-diols.10
10
100
0
oxidantb
–
oxidantb
–
a All the reactions were carried out at 60 °C for 24 h.
b H2O2 (35%), MCPBA or peracetic acid (30%). The reactions were
carried out at 25 °C for 48 h recovering quantitatively the starting ma-
terial.
Nonappreciable differences have been observed between
the reactions carried out with catalytic or stoichiometric
amounts of diselenide. The catalytic role of the (PhSe)2 is
proposed in Scheme 2. The actual catalyst is the strongly
SYNLETT 2010, No. 9, pp 1402–1406
Advanced online publication: 13.04.2010
DOI: 10.1055/s-0029-1219817; Art ID: G05810ST
x
x.
x
x.
2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidation of Alkynes in Aqueous Media
1403
electrophilic PhSe-sulfate produced by the reaction of gel column chromatography the precatalyst (PhSe)2 can
diphenyl diselenide with ammonium persulfate. Reason- be quantitatively recovered and reused.
ably this electrophile, in the presence of water, promotes
an hydroxyselenenylation on the triple bond leading to the
enol 3 that exists in a tautomeric equilibrium with the ke-
tone 4. The excess of ammonium persulfate activates the
Starting from the terminal alkyne 1g the a-ketoaldehyde
2g has not been isolated, and the 1H NMR spectrum of the
crude shows an equilibrium with the hydrated form 7g
(Scheme 3). After silica gel chromatography, using a
phenylselenium moiety to the nucleophilic substitution by
CH2Cl2–MeOH (99:1) mixture as eluent the methoxy
a molecule of water as we reported for the dihydroxyla-
hemiacetal 8g is recovered in 65% yield. It is reasonable
to suppose that the equilibrium between 2g and 7g for the
tion of olefins. The formation of the a-hydroxyketone 6a
(R1 = Ph, R2 = Me) has been hypothesized on the basis of
presence of methanol and the acidic catalysis of SiO2 is
a GC-MS peak [M+] (m/z = 150) observed in the analysis
shifted towards the more stable form 8g (Scheme 3).
effected on the ongoing reaction. In the described experi-
In all the cases the yields obtained in the absence of
mental conditions it is reasonable to suppose a rapid oxi-
(PhSe)2 are much lower.
dation of 6 to afford the corresponding 1,2-dicarbonyl
compound 2. Noteworthy these experimental evidences
suggest that the reaction mechanism, in the presence of
Table 2 Scope of the Reaction
water, is different from those proposed in 1991 by Tiecco
(PhSe)2 cat. (10%)
(NH4)2S2O8
O
et al.3 for similar reactions effected in methanol.
R2
R1
R2
R1
H2O–MeCN (3:1)
60 °C, 24 h
O
1a–g
R1
OH
R2
2a–g
Entry Substrate
Product
Yield (%)
PhSe
H2O
R1
R2
O
Ph
2–
Ph
Me
S2O8
1
1
75
Me
1a
R1
O
O
2a
R2
O
PhSe
20
Pr
(PhSe)2
+
(NH4)2S2O8
Pr
Pr
2
Pr
O
R2
67a
PhSeOSO3H
1b
O
R1
+ SePh
OSO3
2b
–
5
O
20
Ph
Ph
3
59a
H2O
O
O
1c
2c
O
R2
OH
O
R2
O
2–
S2O8
30
Ph
Ph
Pr
4
Pr
77a
R1
O
R1
1d
2
6
2d
Scheme 2 Proposed mechanism
O
Ph
5
Ph
Ph
5
Ph
85b
With the optimized conditions in hand we investigated the
scope of this methodology starting from a series of substi-
tuted alkynes 1a–g. The results are collected in Table 2.
All the reactions were stopped after 24 hours, and the cor-
responding 1,2-dicarbonyl derivatives 2a–g were purified
by flash chromatography and fully characterized on the
basis of GC-MS analysis, 1H NMR and 13C NMR spectral
data. The yields, calculated on the amount of isolated
compounds, range from moderate to good. Starting from
the alkynes 1b–f (entries 2–6) we demonstrated that long-
er reaction time produces a positive effect on the yields.
Even if for a reaction time longer than 200 hours the over-
oxidation seems to be the main process. The alkynes
1a,d,e,g were quantitatively converted into benzoic acid
in seven days. In all the cases after purification on silica
1e
O
2e
O
H17C8
30
H17C8
Me
6
Me
57a
1f
O
2f
OH
OMe
Ph
65c
Ph
H
7
1g
O
8g
a Reaction time 48 h.
b Reaction time 72 h.
c After chromatography SiO2 eluent: CH2Cl2–MeOH.
Synlett 2010, No. 9, 1402–1406 © Thieme Stuttgart · New York

1404
S. Santoro et al.
LETTER
O
intermediate, the selenide 4g was prepared according to
R1
our recently reported procedures.12
H
Treatment of 4g with an excess of ammonium persulfate
in a refluxing mixture of MeCN–H2O (1:3) afforded rap-
idly and quantitatively 8g after purification on silica gel
and methanol (Scheme 4). This reaction was not acceler-
ated by the presence of a catalytic amount of diphenyl di-
selenide indicating that the deselenenylaton is mainly
promoted by the oxidant and not by the electrophilic cat-
alyst.
O
2
OH
(PhSe)2 cat.
(NH4)2S2O8
R1
SiO2, R2OH
R1
H
OR2
H2O–MeCN (3:1)
60 °C, 24 h
1
O
8–11
OH
R1
OH
O
OMe
OH
O
O
2g
7
SePh
2–
S2O8
H2O
SiO2
Scheme 3 Formation of hemiacetals 8–11
MeOH
8g
7g
In order to prove the above proposed mechanism
(Scheme 2) and the involvement of an a-selenoketone as
Scheme 4 Deselenenylation of 4g
Table 3 Preparation of Hemiacetals
Entry
Substrate
R2
Product
Yield (%)
65
OH
Ph
Ph
H
1
Me
OMe
1g
O
8g
OH
Ph
2
3
4
1g
1g
1g
i-Pr
55
–
O
O
9g
–
t-Bu
OH
Ph
menthyl
D-menthyl
30
O
O
10g–11g (1:1)
OH
H17C8
H17C8
H
5
6
Me
30
50
OMe
1h
O
8h
OH
Bu
Bu
H
Me
OMe
1i
O
8i
Br
OH
OMe
Br
H
7
8
Me
Me
60
65
1l
O
8l
MeO
OH
OMe
MeO
H
1m
O
8m
Synlett 2010, No. 9, 1402–1406 © Thieme Stuttgart · New York

LETTER
Oxidation of Alkynes in Aqueous Media
1405
(6) Ahmad, S.; Iqbal, J. J. Chem. Soc., Chem. Commun. 1987,
692.
(7) (a) Wolt, S.; Ingold, C. F. J. Am. Chem. Soc. 1983, 105,
7755. (b) Gopal, H.; Gordon, A. J. Tetrahedron Lett. 1971,
12, 2941.
(8) Girard, P.; Counffignal, R.; Kagan, H. B. Tetrahedron Lett.
1981, 22, 3959.
(9) Yamashita, M.; Suemitsu, R. J. J. Chem. Soc., Chem.
Commun. 1977, 691.
Due to the synthetic versatility as well as to some reported
pharmaceutical application of glyoxal derivatives5,13 we
investigated the selenium-catalyzed oxidation of a series
of terminal alkynes 1g–m. In order to isolate the corre-
sponding hemiacethal 8–11 the crude mixtures were treat-
ed with different alcohols during the purification on silica
gel column.
The results reported in Table 3 indicate that the sterical
demand of the alcohol produces a negative influence on
the yields (entries 2–4) and that an optically pure alcohol
such as D-menthol does not produce a stereoselection dur-
ing the formation of the chiral hemiacetalic carbon lead-
ing to a 1:1 mixture of the possible diastereoisomers 10g
and 11g that cannot be separed by chromatography (entry
4).
(10) Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y.
Tetrahedron Lett. 1995, 36, 1523.
(11) (a) Schroder, M. Chem. Rev. 1980, 80, 187. (b) Muller, P.;
Godey, J. Helv. Chim. Acta 1981, 64, 2531. (c) Chang,
C.-L.; Kumar, M. P.; Liu, R.-S. J. Org. Chem. 2004, 69,
2793. (d) Kashimura, S.; Murai, Y.; Washika, C.; Yoshihara,
D.; Kataoka, Y.; Murase, H.; Shono, T. Tetrahedron Lett.
1997, 38, 6717. (e) Crich, D.; Zou, Y. J. Org. Chem. 2005,
70, 3309. (f) Srinivasan, N. S.; Lee, D. G. J. Org. Chem.
1979, 44, 1574. (g) Dayan, S.; Ben-David, I.; Rozen, S.
J. Org. Chem. 2000, 65, 8816.
(12) (a) Santi, C.; Santoro, S.; Battistelli, B.; Testaferri, L.;
Tiecco, M. Eur. J. Org. Chem. 2008, 5387. (b) Santoro, S.;
Battistelli, B.; Testaferri, L.; Tiecco, M.; Santi, C. Eur. J.
Org. Chem. 2009, 4921.
(13) Fix, J. A.; Pogany, S. A. US 4, 440,740, 1984.
(14) In a typical procedure (PhSe)2 (0.1 mmol) and (NH4)2S2O8 (3
mmol) were suspended in H2O (5 mL) (or in a 3:1 mixure of
H2O–MeCN) and heated at 60 °C for 15 min. To the
resulting red-orange reaction mixture alkyne (1a–m, 1
mmol) was added and stirred for the time reported in
Tables 2 and 3. After the usual workup the crude was
purified by a silica gel chromatography using CH2Cl2 or a
mixture 1:99 R2OH–CH2Cl2 as eluent.
The compounds 8g–m, 9g, 10g, and 11g were isolated by
chromatography and were fully characterized by 1H NMR
and 13C NMR spectroscopy and resulted stable at 0 °C for
several days.
Some selected reactions (on 1a,g,m) were then carried out
in ‘on water’ conditions observing that when starting from
aryl-substituted alkynes results comparable to those ob-
served in the presence of the co-solvent MeCN can be ob-
tained.
In conclusion we reported an unprecedented oxidation of
alkynes promoted by ammonium persulfate in aqueous
medium stressing the catalytic effect of diphenyl dise-
lenide. The proposed procedure14 represents a convenient
way to prepare 1,2-unprotected dicarbonyl derivatives.
From terminal alkynes an interesting conversion of the re-
sulting a-ketoaldehydes to the corresponding hemiacetals
by treatment of the crude with silica gel and different al-
cohols has been observed.
All the compounds, after purification, were fully
characterized by GC-MS, 1H NMR, and 13C NMR
experiments. Physical and spectral data for the products not
previously described in literature are reported below.
2-Hydroxy-2-isopropoxy-1-phenylethanone (9g)
Oil. 1H NMR (400 MHz, CDCl3): d = 8.07 (d, 2 H, J = 7.5
Hz), 7.64 (t, 1 H, J = 7.5 Hz), 7.51 (t, 2 H, J = 7.5 Hz), 5.79
(d, 1 H, J = 8.0 Hz), 4.57 (d, 1 H, J = 8.0 Hz), 4.27 (sept, 1
H, J = 6.4 Hz), 1.35 (d, 3 H, J = 6.4 Hz), 1.28 (d, 3 H, J = 6.4
Hz) ppm. 13C NMR (100.62 MHz, CDCl3): d = 194.5, 134.9,
133.4, 130.0, 129.1, 90.9, 71.0, 24.2, 22.2 ppm. GC-MS:
m/z (relative intensity) = 192 (1), 121 (51), 105 (100), 77
(58), 51 (29).
Acknowledgment
Financial support from M.I.U.R. (Ministero Italiano Università e
Ricerca), National Projects PRIN2007 (Progetto di Ricerca d’Inter-
esse Nazionale), Consorzio CINMPIS, Bari (Consorzio Interuniver-
sitario Nazionale di Metodologie e Processi Innovativi di Sintesi),
University of Perugia, the Erasmus fellowship programme, the
grant ‘British–Italian’ from the British Council/CRUI are gratefully
acknowledged.
1-Hydroxy-1-methoxydecan-2-one (8h)
Oil. 1H NMR (400 MHz, CDCl3): d = 4.86 (d, 1 H, J = 9.2
Hz), 4.10 (d, 1 H, J = 9.0 Hz), 3.50 (s, 3 H), 2.78–2.71 (m, 1
H), 2.57–2.45 (m, 1 H), 1.71–1.62 (m, 2 H), 1.30–1.28 (m,
10 H), 0.89 (t, 3 H, J = 6.0 Hz) ppm. 13C NMR (100.62 MHz,
CDCl3): d = 206.1, 95.5, 55.5, 37.9, 35.5, 31.7, 29.2, 23.0,
14.0 ppm. GC-MS: m/z (relative intensity) = 202 (1), 141
(100), 123 (33) 71 (94), 57 (94).
References and Notes
(1) (a) Santi, C.; Tiecco, M.; Testaferri, L.; Tomassini, C.;
Santoro, S.; Bizzoca, G. Phosphorus, Sulfur Silicon Relat.
Elem. 2008, 183, 956. (b) Santoro, S.; Santi, C.; Sabatini,
M.; Testaferri, L.; Tiecco, M. Adv. Synth. Catal. 2008, 350,
2881.
(2) Freudendahl, D. M.; Santoro, S.; Shahzad, S. A.; Santi, C.;
Wirth, T. Angew. Chem. Int. Ed. 2009, 48, 8409.
(3) Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.;
Bartoli, D. J. Org. Chem. 1991, 56, 4529.
(4) (a) Hillis, L. R.; Ronald, R. C. J. Org. Chem. 1985, 50, 470.
(b) Mattay, J.; Runsik, J. J. Org. Chem. 1985, 50, 2815.
(5) Zuliani, V.; Cocconcelli, G.; Fantini, M.; Ghiron, C.; Rivara,
M. J. Org. Chem. 2007, 72, 4551; and references cited
therein.
1-Hydroxy-1-methoxyhexan-2-one (8i)
Oil. 1H NMR (400 MHz, CDCl3): d = 4.81 (d, 1 H, J = 9.0
Hz), 4.09 (d, 1 H, J = 9.0 Hz) 3.50 (s, 3 H), 2.78–2.65 (m, 1
H), 2.65–2.43 (m, 1 H), 1.65–1.53 (m, 2 H), 1.43–1.23 (m, 2
H), 0.90 (t, 3 H, J = 7.01 Hz) ppm. 13C NMR (100.6 MHz,
CDCl3): d = 206.1, 95.5, 55.5, 37.5, 25.1, 22.2, 13.7 ppm.
GC-MS: m/z (relative intensity) = 146 (13), 119 (10), 97
(36), 85 (60), 77 (50), 70 (55), 57 (100).
2-Hydroxy-2-methoxy-1-(4¢-bromophenyl)-ethanone (8l)
Mp 109–110 °C. 1H NMR (400 MHz, CDCl3): d = 7.95–
7.85 (m, 2 H), 7.65–7.55 (m, 2 H), 5.57 (d, 1 H, J = 9.0 Hz),
4.55 (d, 1 H, J = 9.0 Hz), 3.55 (s, 3 H) ppm. 13C NMR
(100.62 MHz, CDCl3): d = 193.6, 132.6, 131.8, 131.4, 130.4
Synlett 2010, No. 9, 1402–1406 © Thieme Stuttgart · New York

1406
S. Santoro et al.
LETTER
93.4, 55.0 ppm. GC-MS: m/z (relative intensity) = 242 (1),
183 (100), 157 (83), 75 (60), 50 (51).
(m, 2 H), 7.05–6.95 (m, 2 H), 5.59 (s, 1 H), 4.75 (br s, 1 H),
3.90 (s, 3 H) 3.53 (s, 3 H) ppm. 13C NMR (100.62 MHz,
CDCl3): d = 192.6, 165.0, 132.5, 126.0, 114.5, 93.1, 55.9,
54.7 ppm. GC-MS: m/z (relative intensity) = 196 (1), 134
(100), 107 (80), 92 (83), 77 (86), 63 (51), 50 (29).
2-Hydroxy-2-methoxy-1-(4¢-methoxyphenyl)-ethanone
(8m)
Mp 87–88 °C. 1H NMR (400 MHz, CDCl3): d = 8.10–8.05
Synlett 2010, No. 9, 1402–1406 © Thieme Stuttgart · New York

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