Rhodium porphyrin bound to a merrifield resin as heterogeneous catalyst for the cyclopropanation reaction of olefins

Article abstract of DOI:10.3390/molecules21030278

Cyclopropanation reaction is an important tool for obtaining interesting compounds and can be catalyzed by metalloporphyrins with high syn/anti ratio. The catalyst cannot be recycled and is usually lost during chromatographic separation from the two isome

Full text of DOI:10.3390/molecules21030278

molecules
Article
Rhodium Porphyrin Bound to a Merrifield Resin as
Heterogeneous Catalyst for the Cyclopropanation
Reaction of Olefins
Alina Ciammaichella, Valeria Cardoni, Alessandro Leoni and Pietro Tagliatesta *
Dipartimento di Scienze e Tecnologie Chimiche, University of Rome-Tor Vergata, Via della Ricerca Scientifica,
00133 Rome, Italy; alina07@hotmail.it (A.C.); valery881@virgilio.it (V.C.); alessandro.leoni@uniroma2.it (A.L.)
* Correspondence: pietro.tagliatesta@uniroma2.it; Tel.: +39-6-7259-4759; Fax: +39-6-7259-4328
Academic Editors: M. Graça P. M. S. Neves and M. Amparo F. Faustino
Received: 4 February 2016; Accepted: 24 February 2016; Published: 27 February 2016
Abstract: Cyclopropanation reaction is an important tool for obtaining interesting compounds and
can be catalyzed by metalloporphyrins with high syn/anti ratio. The catalyst cannot be recycled and
is usually lost during chromatographic separation from the two isomeric products. In this paper
a meso-tetraphenylporphyrin rhodium(III) chloride was bound to a Merrifield resin and used to
catalyze the cyclopropanation reaction of nine olefins, giving good yields and selectivities of the final
products and for the first time, a partial recycling of the catalyst. This new catalytic system will be
tested in the future for the synthesis of natural products containing cyclopropyl ring.
Keywords: porphyrin catalysts; cyclopropanation reactions; immobilized catalysts
1. Introduction
The cyclopropyl ring is an important organic function due to the presence of such structure
in a number of interesting natural products. Recently, this ring has been found in molecules with
antileukemic activity in vitro
such ring using copper, rhodium and osmium complexes as efficient catalysts for the synthesis of
cyclopropanes from diazocompounds [ ]. Synthetic iron, rhodium and osmium porphyrins have been
also reported as catalysts for the cyclopropanation reaction of simple olefins by ethyldiazoacetate
(EDA) [ ]. Compared with the copper catalysts, like CuCl which preferentially affords the anti
[1]. Several methods have been discovered in the past for obtaining
2
3–9
isomers, the porphyrin catalysts give interesting results in reversing the syn/anti ratio of the products
depending on the nature of the metal. The reaction mechanism of the metalloporphyrins catalyzed
cyclopropanation reactions is not completely elucidated in all the aspects, because of the lability of the
bond between the central metal and the acetate residue.
However, the intermediate of the reaction, shown in Scheme 1, proposed, in the case of rhodium,
by Callot et al. [10] was later studied by Kodadek, who used the NMR spectroscopy for detecting the
possible carbene species [4].
Molecules 2016, 21, 278; doi:10.3390/molecules21030278
www.mdpi.com/journal/molecules

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Scheme 1. Carbene formation mechanism.
During our studies on the catalytic properties of metalloporphyrins, we found that rhodium or
ruthenium complexes of such macrocycles are able to catalyze the cyclooligomerization of arylethynes
to give dimers or trimers, depending from the reaction conditions and substrates [11–15]. We also
showed the possibility to bind a ruthenium porphyrin to the Merrifield resin to give an heterogeneous
system able to catalyze the cyclooligomerization of alkynes with a complete recovery of the catalyst by
simple filtration [16].
The recovering of the catalyst without any tedious column separation, is an important goal
in preparative chemistry because this fact allows us to synthesize large amount of the products
using small quantity of expensive metal complexes. In this paper we will show the possibility to
use an immobilized metalloporphyrin as catalyst for the cyclopropanation of standard olefins, with
good yields in some cases and high syn/anti ratios comparable with those obtained using normal
metalloporphyrins in homogeneous solution [10].
2. Results
The heterogeneous catalyst was obtained by using the well known Merrifield technique [17
which was applied for the first synthesis of peptides in solid phase. The starting porphyrin free base,
was synthesized as reported in the literature [18] and rhodium complex was obtained by a standard
method [19]. After saponification with KOH, the rhodium porphyrin was bound to the solid resin
]
1
2
3
using the Williamson method for the synthesis of ethers [20]. The synthetic steps are reported in
Figure 1.
Figure 1. Synthetic pathway for obtaining the catalyst 4.

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From the data of the elemental analysis obtained for the catalyst
4, we estimate the content of the
rhodium porphyrin to be around 1 mmolar per gram of solid, a value very close to those obtained for
other porphyrin functionalized solids [21 24]. The binding of the catalyst to the solid through the
–
3
ethereal function allows to separate the functionalized resin from the bulk of the reaction by vacuum
filtration and reuse it.
˝
Furthermore, the robustness of the system at the reaction temperature (65 C) was also verified by
UV/vis methods. In fact after 48 h of reaction at this temperature no trace of free metalloporphyrin
was detected in the reaction media by UV/vis spectra. In Table 1 we report the data obtained using
nine simple olefins as substrates in the cyclopropanation reaction catalyzed by 4. The catalytic
activity of the rhodium porphyrin bound to the resin is compared with that obtained from literature
(in parentheses) for styrene, cyclohexene and norbornene.
Table 1. Cyclopropanation of olefins catalyzed by
4 as catalyst compared with the data from
previous papers.
syn/anti Ratio c
d
Yield (%) b
syn/anti Ratio from Lit.
Entry
Substrate
1
2
3
4
5
6
7
8
9
a
Styrene a
4-chlorostyrene
4-methylstyrene
1.12
1.10
1.30
1.85
1.03
1.27
0.9 e
0.72 e
0.15
1.13
-
-
-
0.84
1.28
-
-
-
60(71 d)
55
53
59
4-methoxystyrene
Cyclohexene b
48(62 d)
51(71 d)
45 e
Norbonene b
1-Methylcyclopentene b
2,4,4-Trimethylpentene a
trans-β-Methylstyrene b
70 e
52
Reactions carried out at 65 ˝C in CHCl3. Reactions carried out at 45 ˝C in CH2Cl2 for 12 h with 3.7 mmol
b
c
d
of substrate and 20 mg of catalyst
catalyst. This paper.
4.
Yields determined by GC analysis. From ref. 10 with Rh(III)(TPP)I as
e
In our opinion these results support the fact that there is no influence of the polymeric matrix on
the yields and syn/anti ratios.
3. Discussion
From the data it is clear that the yields of the reactions are slightly lower whilst the syn/anti ratios
are comparable with those obtained using rhodium porphyrins in homogeneous solution. The turnover
numbers are between 103 and 104 for all the reactions, much higher than those previously reported [10].
Only when cyclohexene is used as substrate the syn/anti ratio increases. The recycle of the catalyst
did not give good results in the case of styrene which has been used as standard substrate. In fact the
yield decreases to 42% in the second run but this value remains almost constant for the third and fourth
run, showing that the catalyst retains part of its activity. It should be noted that to our knowledge,
this is the first example of the reuse of a catalyst for the cyclopropanation reaction. Furthermore,
the lower yield reported in the text for the reuse of the catalyst
not much affected by the temperature. In fact a yield of 50% for the reaction on styrene using
after a thermal treatment before the use, is almost comparable to that reported in Table 1, entry 1.
Control experiments were performed using catalyst and in homogeneous solution and after
4 after the first run, seems to be
4
2
3
4
˝
treatment at 65 C in chloroform for 6 h, using styrene as standard olefin. In Table 2 the results of such
reactions are reported. In Supplementary Materials, experimental procedure and characterization of
new compounds are reported.

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Table 2. Cyclopropanation of styrene catalyzed by 2, 3 and 4.
Yield(%) a,b
Entry
Catalyst
syn/anti Ratio
1
2
3
2
3
59
58
50
1.04
0.92
1.06
c
4 c
b
Reactions carried out at 65 ˝C in CHCl3. Yields determined by GC analysis. After treatment of the catalyst
a
at 65 ˝C in chloroform for 6 h.
Both yield and syn/anti ratio for entries 1 and 2 are comparable with those obtained with catalyst
4
in the same experimental conditions (see Table 1, entry 1).
4. Materials and Methods
4.1. General
UV/vis spectra were recorded with a Varian Cary 10 spectrophotometer (Palo Alto, CA, USA).
1H-NMR spectra were recorded on a Bruker AM 400 spectrometer (Billerica, MA, USA) as CDCl3
solutions. Chemical shifts are given in ppm from tetramethylsilane (TMS) and are referenced against
residual solvent signals. Mass spectra (FAB) were recorded on a VG-Quattro spectrometer (Fisons,
Manchester, UK) using 3-nitrobenzylalcohol (NBA) as a matrix. The products yield and the isomeric
ratios for all the reactions were determined by GC analyses (Waltham, MA, USA) performed on a Focus
Thermo instrument equipped with a 15 m Restek MTX-5 capillary column and a FID detector. Chemical
yields were determined by adding a suitable internal standard (decane or dodecane) to the reaction
mixture at the end of each experiment and were reproducible within ˘2% for multiple experiments.
4.2. Chemicals
All the reagents and solvents (Aldrich, St. Louis, MO, USA) were of the highest analytical grade
and used without further purification.
Silica gel 60 (70–230 and 230–400 mesh, Merck, Darmstadt, Germany) was used for column
chromatography. High-purity grade nitrogen gas was purchased from Rivoira.
The free base 5-(4-acetoxymethylphenyl)-10,15,20-triphenylporphyrin was synthesized by
literature methods [18].
Rhodium(III) meso-tetraphenylporphyrin chloride was obtained as reported in the literature. [19
]
Analytical data for cyclopropane derivatives of 4-chloro, 4-methyl and 4-methoxystyrene are reported
in the literature [25].
5. Conclusions
In synthesis we have prepared a new heterogeneous catalytic system using a rhodium porphyrin
immobilized on the Merrifield resin and used it for the cyclopropanation of nine standard olefins.
The catalyst can be separated from the bulk of the reaction by a simple filtration and retains part of its
catalytic activity. New studies on the use of similar strategies for obtaining heterogeneous porphyrin
catalysts for other reactions are currently in progress.
Supplementary Materials: Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/
21/3/278/s1.
Author Contributions: Pietro Tagliatesta conceived and designed the experiments; Alina Ciammaichella and
Valeria Cardoni performed the experiments; Alessandro Leoni contributed reagents/materials/analysis tools;
Pietro Tagliatesta wrote the paper.
Conflicts of Interest: The authors declare no conflict of interest.

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