Isomerization and application of phospholene oxides

Article abstract of DOI:10.1080/10426507.2018.1553043

In this research, an investigation of the isomerization and the applications of 3-phospholene oxides were elaborated. The isomerization of 3-phospholene oxides to 2-phospholene oxides was investigated under thermal condition. The application of bases and acids was also tested in this reaction. Moreover, the isomerization was also elaborated via the formation of halophosphonium salt intermediates. The 3-phospholene oxides were deoxygenated and transformed to the corresponding palladium complexes.

Full text of DOI:10.1080/10426507.2018.1553043

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Isomerization and application of phospholene
oxides
Réka Herbay, Nikolett Péczka, Gábor Györke, Péter Bagi, Elemér Fogassy &
György Keglevich
To cite this article: Réka Herbay, Nikolett Péczka, Gábor Györke, Péter Bagi, Elemér Fogassy
& György Keglevich (2018): Isomerization and application of phospholene oxides, Phosphorus,
Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2018.1553043
To link to this article: https://doi.org/10.1080/10426507.2018.1553043
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2018.1553043
Isomerization and application of phospholene oxides
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Reka Herbay, Nikolett Peczka, Gabor Gyorke, Peter Bagi, Elemer Fogassy, and Gyorgy Keglevich
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, Hungary
ABSTRACT
ARTICLE HISTORY
Received 28 September 2018
Accepted 24 November 2018
In this research, an investigation of the isomerization and the applications of 3-phospholene
oxides were elaborated. The isomerization of 3-phospholene oxides to 2-phospholene oxides was
investigated under thermal condition. The application of bases and acids was also tested in this
reaction. Moreover, the isomerization was also elaborated via the formation of halophosphonium
salt intermediates. The 3-phospholene oxides were deoxygenated and transformed to the corre-
sponding palladium complexes.
KEYWORDS
3-phospholene oxide;
2-phospholene oxide;
halophosphonium salt;
isomerization; palladium
complex
GRAPHICAL ABSTRACT
Introduction
the 3-phospholene oxides (1) to the corresponding 2-
phospholene derivatives (2).
Phospholene oxides form an important class, as they are
valuable starting materials for ligands.[1] The preparation of
the 3-phospholene core is well-established,[2–7] but the 2-
phospholene derivatives can only be prepared by a few
methods,[2, 8] despite the fact that the 2-phospholene oxides
(2) are considered as the main starting materials for
phospha-sugars having antitumor activity.[9–11] In our
research group, 2-phospholene oxides (2) were formed as
side products under thermal or MW conditions during the
alkylating esterification of cyclic phosphinic acids or the
acidic hydrolysis of phosphinic acid esters.[12–14] The forma-
tion of the 2-phospholene derivatives was also observed in
Platinum complexes incorporating 3-phospholene ligands
have already been synthesized and applied in hydroformyla-
tion.[16–18] However, the preparation of the corresponding
palladium complexes (6) is still an unexplored field.
Results and discussion
Investigation of isomerization of 1-substituted-3-methyl-
3-phospholene oxides (1) to 2-phospholene oxides (2)
As the first step of this study, we investigated whether the
isomerization occurs at elevated temperature without
the preparation of phospholene borane complex via the any reagent. It was concluded, that the isomerization of the
chlorophosphonium salts (3 and 4).[15] These observations 3-phospholene oxides (1) did not occur under reflux condi-
prompted us to investigate in detail the isomerization of tions in toluene, dimethylformamide or dimethyl sulfoxide.
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CONTACT Reka Herbay
herbay.reka@mail.bme.hu
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics,
Budapest, Hungary.
ß 2018 Taylor & Francis Group, LLC

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R. HERBAY ET AL.
Scheme 1. Investigation of isomerization without using solvent and reagent.
and reagent. The optimal conditions were 50 ꢀC and 2.5 d,
and the isomerization was almost complete in every case
(Scheme 3).
In our previous study, the isomerization of cyclic
chloro-3-phospholenium salts (3) to the corresponding chloro-
2-phospholenium species (4) was identified as a side reaction.[15]
Thus, the isomerization of 3-phospholene oxides (1) was also
investigated via the formation of chloro-phospholenium salts
(3 and 4). The 1-substituted-3-phospholene oxides (1) were
converted to chloro-3-phospholenium salts (3) using oxalyl
chloride. The cyclic chlorophosphonium salts (3) were stirred at
50 ꢀC in sealed tube to promote the formation of the thermodi-
namically more stable chloro-2-phospholenium salts (4). The
reaction mixture was quenched with water to give the corre-
sponding 2-phospholene oxides (1) (Scheme 4).
Scheme 2. Investigation of isomerization in the presence of base.
However, when the 3-phospholene oxides (1) were stirred at
200 ꢀC without any solvent for five days, the isomerization
ratio was up to 82% in every case (Scheme 1).
The next step was the investigation of the effects of bases
on the reaction. During the optimization reactions, several
organic or inorganic bases were tested. It was concluded,
that carbonates, such as K2CO3 and Cs2CO3 are sufficient
bases for the isomerization. The highest isomerization ratio
(84%) was reached by refluxing the phenyl-3-methyl-3-
phospholene oxide (1a) in dimethyl-formamide using 2
equivalent of Cs2CO3 in the presence of TEBAC (triethyl-
benzyl-ammonium chloride). It was also concluded, that the
isomerization ratio could not be increased by changing the
reaction conditions (Scheme 2).
The isomerization was then investigated in the presence
of acids. The 1-phenyl-3-phospholene-oxide (1a) was
refluxed in different solvents in the presence of several
organic or inorganic acids, but no isomerization was
observed. Then, the isomerization of 3-phospholene oxides
Palladium complex formation of cyclic phosphines
In our research group, the deoxygenation and the transition
metal complex formation of cyclic phosphines have been
investigated for decades.[1] The platinum complexes of 3-
phospholenes were also prepared previously, and they were
applied as catalysts in the hydroformylation of styrene.[16–18]
In the literature, the palladium complexes of 3-phospholenes
(6) were unknown, so our aim was the preparation of these
compounds (6). The deoxygention of phospholene oxides
(1) was accomplished according to the method developed by
us.[17,18] The 3-phosphelenes (5) thus prepared were reacted
with bis(benzonitrile)palladium(II) to give the corresponding
(1) was accomplished using methanesulfonic acid as solvent palladium complexes (6) (Scheme 5).
Scheme 3. Investigation of isomerization using methanesulfonic acid.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Scheme 4. Investigation of isomerization via the formation of chloro phosphonium salts.
Scheme 5. Preparation of palladium complexes from racemic phospholene oxides.
Phospholenes and Phospholene Oxides. J. Org. Chem. 1968, 33,
1034–1041.
Conclusions
In summary, the isomerization of 3-phospholene oxides (1)
to 2-phospholene oxides (2) was accomplished. Several
methods were evaluated, among which two afforded the 2-
phospholene oxides (2) in good or excellent yields.
Palladium complexes incorporating 3-phospholene (6)
[9] Fujie, M.; Nakamura, S.; Asai, K.; Niimi, T.; Yamashita, J.;
Kiyofuji, K.; Shibata, K.; Suzuki, M.; Aoshima, R.; Urano, T.;
et al.
Evaluation
A
Novel Phospha Sugar Analogue: Synthesis and
of 2,3-dibromo-3-methyl-1-phenylphospholane
1-oxide as a New Class of Potential Anti-Proliferative Materials
for Leukemia Cells. Heterocycl. Commun. 2009, 15, 273–278.
[10] Yamashita, M.; Iida, A.; Mizuno, H.; Miyamoto, Y.; Morishita,
T.; Sata, N.; Kiguchi, K.; Yabui, A.; Oshikawa, T. Reactions of
2-phospholene 1-oxides with Bromine in Some Media: Facile
Preparation of Bromohydrin Derivatives of 2-Phospholenes.
Heteroat. Chem. 1993, 4, 553–557. DOI: 10.1002/hc.520040606.
[11] Yamashita, M.; Reddy, V. K.; Rao, L. N.; Haritha, B.; Maeda,
M.; Suzuki, K.; Totsuka, H.; Takahashi, M.; Oshikawa, T. An
Efficient Approach towards the Stereospecific Synthesis of
Epoxides from Phospholene Oxides. Tetrahedron Lett. 2003, 44,
2339–2341. DOI: 10.1016/S0040-4039(03)00255-7.
ligands were also synthesized.
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