Magnesium bis(monoperoxyphthalate) hexahydrate as mild and efficient oxidant for the synthesis of selenones

Article abstract of DOI:10.3762/bjoc.10.127

A new, efficient and mild method for the direct oxidation of selenides to selenones using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) has been developed. Noteworthy this transformation proceeds at room temperature, employs a cheap and safety oxi

Full text of DOI:10.3762/bjoc.10.127

Magnesium bis(monoperoxyphthalate) hexahydrate
as mild and efficient oxidant for the
synthesis of selenones
Andrea Temperini*1, Massimo Curini1, Ornelio Rosati1 and Lucio Minuti2
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 1267–1271.
1Dipartimento di Scienze Farmaceutiche, Università di Perugia, via
del Liceo 1, 06123 Perugia, Italy and 2Dipartimento di Chimica,
Biologia e Biotecnologia, Università di Perugia, via Elce di Sotto 8,
06123 Perugia, Italy
doi:10.3762/bjoc.10.127
Received: 10 March 2014
Accepted: 13 May 2014
Published: 02 June 2014
Email:
Andrea Temperini* - andrea.temperini@unipg.it
Dedicated to the memory of Professor Marcello Tiecco.
Associate Editor: T. J. J. Müller
* Corresponding author
Keywords:
© 2014 Temperini et al; licensee Beilstein-Institut.
License and terms: see end of document.
heterocycles; monoperoxyphthalate; oxidation; selenides; selenones
Abstract
A new, efficient and mild method for the direct oxidation of selenides to selenones using magnesium bis(monoperoxyphthalate)
hexahydrate (MMPP) has been developed. Noteworthy this transformation proceeds at room temperature, employs a cheap and
safety oxidant and has a broad functional group tolerance. Moreover, the produced selenones could be useful intermediates for the
synthesis of different heterocyclic compounds.
Introduction
Organoselenium compounds have received considerable atten-
tion in recent times because they are versatile reagents or inter-
mediates in organic synthesis [1]. Particularly, alkyl phenyl
selenones [2,3] represent a valuable compound class due to the
ability of the phenylselenonyl group to behave as a good
Scheme 1: General transformation of selenides to selenones.
leaving group in substitution reactions (Scheme 1). Thus, the
development of efficient and mild methods for their synthesis is
of considerable interest.
vantages such as harsh reaction conditions and limited struc-
tural features of the substrates; thus, potassium hydrogen
A few previous papers report the synthesis of selenones 2 by persulfate [6] (Oxone) and m-chloroperoxybenzoic acid [4,7]
oxidation of the corresponding selenides 1 with potassium (MCPBA) have been employed for the oxidation of different
permanganate [4], trifluoroacetic acid [4] and hydrogen alkyl phenyl selenides to the corresponding selenones. Since the
peroxide in trifluoroethanol with stoichiometric amounts of phenylselenonyl group is an excellent leaving group, selenone 2
phenylseleninic acid [5]. These methods suffer of several disad- readily undergoes SN2 type substitution reactions with common
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Beilstein J. Org. Chem. 2014, 10, 1267–1271.
nucleophiles [7,8] as shown in Scheme 2. A wide range of
heterocyclic compounds can be obtained by intramolecular
nucleophilic substitution reactions e.g. epoxides from
β-hydroxy phenyl selenides [9,10], N-benzoyl- and N-tosyl-1,3-
oxazolidin-2-ones from β-hydroxyalkyl phenyl selenides [11],
N-arenesulfonylazetidines from γ-(phenylseleno)alkyl arylsul-
fonamides [12], N-acylaziridines [13], 1,3-oxazolines, dihy-
drooxazine and pyrrolidines from acylamino phenyl selenides
[14]. Interestingly, the intramolecular substitution reaction of a
phenylselenonyl group was used on enantioenriched γ-hydrox-
yalkyl phenyl selenides to obtain optically active 2-substituted
tetrahydrofurans [15] (see Scheme 2).
Scheme 2: Phenylselenone 2 as useful leaving group for the syn-
thesis of different organic molecules.
In this article, we investigated the use of magnesium
bis(monoperoxyphthalate) hexahydrate (MMPP) as a new
oxidant for the straightforward conversion of selenides 1 to
selenones 2 under mild experimental conditions. Magnesium Results and Discussion
bis(monoperoxyphthalate) hexahydrate is a cheap commer- Firstly, a solution of selenide 1a in ethanol was treated with
cially available, relatively stable and easy to use oxidant and it 2.4 equiv of MMPP at room temperature to obtain the corres-
has been employed for the selective oxidation of sulfides to the ponding selenone 2a in 94% yield (Table 1, entry 1). The
corresponding sulfoxides, for the preparation of α-methylene- known oxidation of selenide 1a with MCPBA in dichloro-
cyclohexane [16] and glycosyl sulfoxides [17]. Compared to the methane [4] gave the corresponding selenone in 68% yield. It is
widely used peroxy acid MCPBA, MMPP has similar chemical noteworthy that the reaction byproduct magnesium phthalate is
properties, but it is a halogen-free reagent and it is considered water soluble and easy to separate during work-up; acidifica-
safer to use in both small- and large-scale reactions [18]. The tion of the water phase and extraction with dichloromethane
only disadvantage of MMPP is its poor solubility in non-polar allows to recover the pure phthalic acid in excellent yield.
solvents such as dichloromethane. To the best of our
knowledge the use of MMPP for the over oxidation of the sele- This protocol was then extended to the oxidation of selenides
nium atom to the corresponding selenone was not reported 1b–d. The reactions were monitored by simple TLC and good
before.
to excellent yields of the selenones 2b–d were obtained after
Table 1: Oxidation of selenides 1a–d to selenones 2a–d with MMPP.
Entry
1
Selenide
Solvent
EtOH
Time (h)
3
Selenone
Yield (%)
94
1a
2a
2
THFa
3
54
1b
1c
1d
2b
3
4
THFa
EtOH
2
1
80
63
2c
2d
aDipotassium hydrogen phosphate was added.
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Beilstein J. Org. Chem. 2014, 10, 1267–1271.
simple work-up without additional purification. Structures of corresponding methyl cyclopentyl ketone deriving from ring
compounds 2a,b and 2d were assigned by their IR and NMR contraction [20]. On the other hand the oxidation of 1b with
spectra. The NMR and IR spectra data were in agreement with Oxone in methanol and water gave the β-methoxy alcohol
those of similar compounds reported in the literature [6]. through transformation of the C–Se bond into a C–O bond even
Despite the low solubility of MMPP in tetrahydrofuran, the oxi- in the presence of a weak nucleophile like the hydroxy ion [6].
dation of selenides 1b and 1c in tetrahydrofuran and in the pres- The oxidation of γ-(phenylseleno)alkyl tosylamide 1d with
ence of dipotassium hydrogen phosphate as base, proceeded MMPP (2.4 equiv) in ethanol afforded the corresponding
smoothly and let us to obtain selenones 2b and 2c in good selenone 2d in 63% yield. Instead, when the same reaction was
yields (Table 1, entry 2 and 3). Selenone 2c was previously carried out in tetrahydrofuran, the undesirable olefine derived
obtained in 60% yield by reaction of 1c with MCPBA in di- from the β-elimination of selenoxide intermediate was formed
chloromethane [19]. Interestingly, selenone 2b was obtained for as the main product. Otherwise, when the same reaction was
the first time by our oxidation procedure performed in tetrahy- conducted in the presence of powdered potassium hydroxide,
drofuran as solvent and fully characterized by classical spectro- selenone intermediate 2d containing the nucleophilic tosyl-
scopic analysis and high resolution mass spectrometry. amide group, readly underwent selective cyclization to give
However, it is important to note that the oxidation of selenide unsubstituted N-tosylazetidine (3d) in 55% yield (Table 2, entry
1b with MCPBA in methanol did not give selenone 2b but the 1), lower than the yield obtained with MCPBA (100%, [14]).
Table 2: Oxidative cyclization with MMPP of functionalized selenides 1e–j to heterocycles 3e–j.
Entry
1
Selenide
Solvent
EtOHa
Time (h)
3
Selenone
Yield (%)
55
1d
3d
3e
2
3
4
THFb
MeOH
MeOH
16
4
77
84
67
1e
1f
3f
7
1g
3g
5
THFb
10
94
3h
1h
6
7
THFc
6
7
82
69
3i
3j
1i
1j
MeOH
aPotassium hydroxide was added. bDipotassium hydrogen phosphate was added. cCyclized in acetone with powdered potassium carbonate.
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Beilstein J. Org. Chem. 2014, 10, 1267–1271.
An experiment to replicate the result of Toshimitsu [14] furan 3j was obtained in 69% yield (Table 2, entry 7) as the sole
employing MCPBA and potassium hydroxide in ethanol, product. It is interesting to note that N-heterocyclic compounds
produced compound 3d with a comparable yield of 54%. When 3d and 3f–j are not obtained when Oxone [6] is employed as
our procedure was extended to selenides 1e–j containing a oxidant. In these cases the products obtained were the corres-
nucleophilic nitrogen or oxygen atom, the MMPP oxidation of ponding selenoxides and the β-elimination products.
these selenides, gave the corresponding selenone intermediates
which readily undergo intramolecular SN2 type substitution Conclusion
reactions to afford a range of heterocyclic compounds (Table 2, In summary, compared to the widely used oxidant MCPBA,
entries 2–7) and benzeneseleninic acid. Thus, the oxidation of MMPP is cheap, stable in the solid state, safer in handling and
β-hydroxyalkyl phenyl selenide 1e gave, in tetrahydrofuran and easier to use. Furthermore, the water soluble reaction byprod-
in the presence of dipotassium hydrogen phosphate, the corres- ucts magnesium phthalate and benzeneseleninate anion are gen-
ponding oxirane 3e in 77% yield, resembling the previously erally easy to separate during work-up; the former could be
reported one by oxidation with MCPBA (73% [9]). The MMPP recovered without additional purification as phthalic acid up to
oxidation of β-benzoylamino phenyl selenide 1f in methanol 85%, and the latter as diphenyl diselenide [21]. Finally, the oxi-
afforded exclusively the 1,3-oxazine 3f in excellent yield dation of selenides to selenones described here is compatible
(84%).
with different functional groups, occurs under mild reaction
conditions and the yields are comparable with those obtained by
This result is in accordance with data reported by Toshimitsu means of peroxy acid MCPBA. Application of the reported oxi-
[14] for a structural similar compound oxidized with MCPBA. dation methodology to the synthesis of bioactive molecules is
In this case the authors stated that the cyclization by the oxygen currently under investigation.
atom was very fast and no β-methoxyamide derivative was
detected when methanol was employed as the reaction solvent.
Supporting Information
Similarly the dihydrooxazine 3g [14] was easily obtained in
good yield by the oxidative cyclization of the acylamino phenyl
Supporting Information File 1
selenide 1g with MMPP in methanol (Table 2, entry 4) although
in lower yield than reported before (90% [14]). As reported in
Table 2 (entries 5 and 6), the N-tosyl-1,3-oxazolidin-2-one [11]
3h and the N-benzoyl-1,3-oxazolidin-2-one [11] 3i were
easily obtained by MMPP oxidation of the corresponding
β-carbamoyloxyalkyl phenyl selenides 1h and 1i in tetrahydro-
furan. The N-substituted-1,3-oxazolidin-2-ones 3h and 3i were
obtained in 94% and 82% yields respectively as a result of the
intramolecular displacement of the phenylselenonyl group by
the nitrogen atom of the carbamic group. These results are in
accordance with precedent oxidation–cyclization reactions
performed with MCPBA (96% and 88% respectively) [11]. The
presence of the phenylselenone intermediate in the above reac-
tions was already and unambiguously demonstrated [11]. On
the other hand, the oxidation of 1d with MMPP in ethanol
allowed to isolate and to fully characterize (high resolution
mass spectra and NMR analysis) the expected selenone inter-
mediate 2d (Table 1, entry 4). Finally our procedure was
applied to the synthesis of 2-substituted tetrahydrofuran 3j
which was previously obtained in 77% yield employing
MCPBA in tetrahydrofuran [15]. The oxidation of 1j with
MMPP in tetrahydrofuran proceeded smoothly to give 3j in
poor yield besides the olefine derived from the elimination of
the selenoxide intermediate. The use of methanol as the solvent
in the oxidative-cyclization reaction of 1j not only favoured the
oxidation reaction, but also suppressed the β-elimination side
reaction of the selenoxide intermediate [14]. Thus tetrahydro-
Experimental procedures, characterization data and copies
of 1H and 13C NMR spectra.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-127-S1.pdf]
Acknowledgements
The authors thank MIUR, Italy, National Project PRIN
20109Z2XRJ_010 and the Fondazione Cassa Risparmio Perugia
(Project 2012.0122.021) for the financial support.
References
1. Wirth, T., Ed. Organoselenium Chemistry: Synthesis and Reactions;
Wiley-VCH: Weinheim, Germany, 2012.
2. Lattanzi, A. Oxidation of Sulfur, Selenium, and Tellurium. In
Comprehensive Organic Synthesis II, 2nd ed.; Knochel, P.;
Molander, G. A., Eds.; Elsevier: Oxford, UK, 2014; Vol. 7, pp 837–879.
doi:10.1016/B978-0-08-097742-3.00734-5
3. Drabowicz, J.; Mikołajczyk, M. Selenium at higher oxidation. In
Organoselenium Chemistry: Modern Developments in Organic
Synthesis; Wirth, T., Ed.; Topics in Current Chemistry, Vol. 208;
Springer: Berlin, 2000; pp 143–176.
4. Krief, A.; Dumont, W.; Denis, J.-N.; Evrard, G.; Norberg, B.
J. Chem. Soc., Chem. Commun. 1985, 569–570.
doi:10.1039/c39850000569
5. Krief, A.; Dumont, W.; De Mahieu, A. F. Tetrahedron Lett. 1988, 29,
3269–3272. doi:10.1016/0040-4039(88)85139-6
6. Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.
J. Org. Chem. 1995, 60, 8412–8413. doi:10.1021/jo00131a018
1270

Beilstein J. Org. Chem. 2014, 10, 1267–1271.
7. Uemura, S.; Fukuzawa, S.-i.; Toshimitsu, A.
J. Chem. Soc., Chem. Commun. 1983, 1501–1502.
doi:10.1039/c39830001501
8. Krief, A.; Dumont, W.; Denis, J.-N. J. Chem. Soc., Chem. Commun.
1985, 571–572. doi:10.1039/c39850000571
9. Uemura, S.; Ohe, K.; Sugita, N. J. Chem. Soc., Chem. Commun. 1988,
111–112. doi:10.1039/c39880000111
10.Krief, A.; Dumont, W.; Laboureur, J. L. Tetrahedron Lett. 1988, 29,
3265–3268. doi:10.1016/0040-4039(88)85138-4
11.Tiecco, M.; Testaferri, L.; Temperini, A.; Bagnoli, L.; Marini, F.;
Santi, C. Chem.–Eur. J. 2004, 10, 1752–1764.
doi:10.1002/chem.200305497
12.Tiecco, M.; Testaferri, L.; Temperini, A.; Terlizzi, R.; Bagnoli, L.;
Marini, F.; Santi, C. Org. Biomol. Chem. 2007, 5, 3510–3519.
doi:10.1039/b712861d
13.Ward, V. R.; Cooper, M. A.; Ward, A. D. J. Chem. Soc., Perkin Trans. 1
2001, 944–945. doi:10.1039/b102468j
14.Toshimitsu, A.; Hirosawa, C.; Tanimoto, S.; Uemura, S.
Tetrahedron Lett. 1992, 33, 4017–4020.
doi:10.1016/0040-4039(92)88089-N
15.Minuti, L.; Barattucci, A.; Bonaccorsi, P. M.; Di Gioia, M. L.; Leggio, A.;
Siciliano, C.; Temperini, A. Org. Lett. 2013, 15, 3906–3909.
doi:10.1021/ol401653w
16.Chen, C.; Crich, D. Tetrahedron Lett. 1992, 33, 1945–1948.
doi:10.1016/0040-4039(92)88109-I
17.Chen, M.-Y.; Patkar, L. N.; Lin, C.-C. J. Org. Chem. 2004, 69,
2884–2887. doi:10.1021/jo035698o
18.Heaney, H. Novel organic peroxygen reagents for use in Organic
Synthesis. In Organic peroxygen chemistry; Herrmann, W. A., Ed.;
Topics in Current Chemistry, Vol. 164; Springer: Berlin, 1993; pp 1–19.
19.Ward, A. D.; Ward, V. R.; Tiekink, E. R. T.
Z. Kristallogr. - New Cryst. Struct. 2001, 216, 553–554.
20.Uemura, S.; Fukuzawa, S.-i. J. Chem. Soc., Perkin Trans. 1 1985,
471–480. doi:10.1039/p19850000471
21.Tiecco, M.; Testaferri, L.; Temperini, A.; Terlizzi, R.; Bagnoli, L.;
Marini, F.; Santi, C. Synthesis 2005, 579–582.
doi:10.1055/s-2005-861783
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