Update: An efficient synthesis of poly(ethylene glycol)-supported iron(II) porphyrin using a click reaction and its application for the catalytic olefination of aldehydes

Article abstract of DOI:10.1002/adsc.201100289

The facile synthesis of polyethylene glycol (PEG)-immobilized iron(II) porphyrin using a copper-catalyzed azide-alkyne [3+2] cycloaddition "click" reaction is reported. The prepared complex 5 (PEG-C ₅₁H₃₉FeN₇O) was found to be an efficient catalyst for the selective olefination of aldehydes with ethyl diazoacetate in the presence of triphenylphosphine, and afforded excellent olefin yields with high (E) selectivities. The PEG-supported catalyst 5 was readily recovered by precipitation and filtration, and was recycled through ten runs without significant activity loss. Copyright

Full text of DOI:10.1002/adsc.201100289

UPDATES
DOI: 10.1002/adsc.201100289
Update: An Efficient Synthesis of Poly(ethylene glycol)-Support-
ed Iron(II) Porphyrin Using a Click Reaction and its Application
for the Catalytic Olefination of Aldehydes
Tamilselvi Chinnusamy,a Valentin Rodionov,b Fritz E. Kꢀhn,c and Oliver Reisera,*
a
Institut fꢀr Organische Chemie, Universitꢁt Regensburg, Universitꢁtsstr. 31, 93053 Regensburg, Germany
Fax : (+49)-(0)941-943-4121; e-mail: oliver.reiser@chemie.uni-regensburg.de
KAUST Catalysis Center (KCC), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudia
b
Arabia
c
Molekulare Katalyse, Fakultꢁt fꢀr Chemie der Technischen Universitꢁt Mꢀnchen, Lichtenbergstrasse 4, 85747 Garching,
Germany
Received: April 17, 2011; Revised: January 23, 2012; Published online: May 9, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201100289.
Abstract: The facile synthesis of polyethylene
glycol (PEG)-immobilized iron(II) porphyrin using
a copper-catalyzed azide-alkyne [3+2]cycloaddi-
tion “click” reaction is reported. The prepared com-
plex 5 (PEG-C51H39FeN7O) was found to be an effi-
cient catalyst for the selective olefination of alde-
hydes with ethyl diazoacetate in the presence of tri-
phenylphosphine, and afforded excellent olefin
yields with high (E) selectivities. The PEG-support-
ed catalyst 5 was readily recovered by precipitation
and filtration, and was recycled through ten runs
without significant activity loss.
and filtration upon completion. Among the various
polymeric supports, poly(ethylene glycol)s (PEGs)
hold a prominent position due to their accessibility,
facile functionalization, inexpensive nature, and their
unique property of being soluble in most common or-
ganic solvents but also being insoluble in some such
as diethyl ether.[2]
Metalloporphyrins, owing to their high reactivity
and remarkable stability, have been recognized as ef-
ficient and versatile catalysts, which find a broad spec-
trum of applications in organic synthesis.[3] However,
the homogeneous nature of these catalysts renders
their recovery and recycling difficult. This can be
overcome by anchoring them to a PEG support via
a covalent attachment.[4]
Keywords: copper-catalyzed azide-alkyne [3+2]cy-
cloaddition “click” reaction; CuAAC; iron porphy-
rin; olefination; polyethylene glycol (PEG); sup-
ported catalysts
The copper-catalyzed [3+2][5] azide-alkyne[6] cy-
coaddition (CuAAC), a quintessential “click” reac-
tion, is becoming an indispensable tool for ligating
functionalized molecule fragments, and has been well
acknowledged for the preparation of functionalized
polymers, dendrimers, diverse scaffolds and immobi-
The need to improve both the efficiency and environ- lized catalysts and reagents.[7] In spite of reports on
mental acceptability of catalytic processes has created the CuAAC for directly immobilizing metal com-
considerable interest in the development of supported plexes on polymer support,[8] its potential for immobi-
metal catalysts and reagents that maintain high selec- lizing metalloporphyrins on polymer supports remains
tivity and reactivity in organic synthesis.[1] Since tran- unexplored.
sition metal complexes are often expensive and diffi-
We report here the successful synthesis of a PEG-
cult to prepare, immobilization on polymeric supports immobilized iron(II) porphyrin using CuAAC, and
provides a means to make them easier to handle and explore its catalytic activity for the olefination of al-
to recycle. Soluble organic polymers have recently dehydes using ethyl diazoacetate in the presence of
emerged as most promising and convenient supports triphenylphosphine. This follows our initial report in
for the immobilization of transition metal complexes. which the covalent attachment of propargylated PEG
Reactions promoted by a soluble, polymer-supported 4 with azidoporphyrine 2 had been attempted.[9] How-
catalyst can consequently be run under homogeneous ever, as subsequently proved, due to a failure in the
conditions, while the catalyst itself can be easily re- synthesis of 4 only a mixture of MeOPEG 3 and 2
covered from the reaction mixture by precipitation was present in solution that, nevertheless, could be
Adv. Synth. Catal. 2012, 354, 1827 – 1831
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1827

Tamilselvi Chinnusamy et al.
UPDATES
Scheme 1. Synthetic route to PEG-immobilized iron porphyrin 5 using CuAAC.
used as a catalyst for the olefination of aldehydes and
could be subsequently recovered as whole by precipi- the olefination of aldehydes[13] with ethyl diazoacetate
tation from the reaction mixture. in the presence of triphenylphosphine as a reducing
The unsymmetrically substituted azido porphyrin agent (Table 1, Scheme 2).
The catalytic potential of conjugate 5 was tested for
1 was readily prepared according to a literature pro-
In all cases, excellent conversion, high yields and
cedure.[10] The free porphyrin 1 was then metallated (E)-selectivity were achieved, being comparable to
in presence of 2,6-dimethylpyridine with ferrous chlo- those reported for the homogeneous iron porphyrin[13]
ride in CHCl3/MeOH to give “clickable” iron porphy- catalysts with the added advantages of facile recovery
rin 2 in 90% yield (Scheme 1). Attachment of 2 to of 5 from the reaction mixture and reusability of the
PEG monomethyl ether (Mn ~5 kgmolÀ1) 3 was ach- PEG-bound catalyst. Whereas also a simple mixture
ieved in two steps: Propargylation of 3[11] gave rise to of MeOPEG 3 and aziodoporphyrine 2 can be recov-
4, which on subsequent copper(I) iodide-catalyzed cy- ered with good efficiency but with leaching of iron up
cloaddition with 2 resulted in covalently attached to 200 ppm into the products in each cycle, the recov-
PEG-immobilized iron(II) prophyrin 5. After extrac- ery of 5 was clearly superior with only minimum
tion with EDTA solution to remove the copper cata- leaching [<2 ppm in all cases (Table 2) as determined
lyst, the reddish-brown colored PEG-porphyrin conju- by ICP-MS] of iron into the products.
gate 5 was obtained by precipitation with diethyl
Among the various aromatic aldehydes studied,
ether. The complex loading was determined to be those substituted with electron-withdrawing substitu-
0.07 mmol/g[12] based on the nitrogen content deter- ents (Table 1, entries 8–12) were found to be more re-
mined by elemental analysis, being in good agreement active, and required shorter reaction times than ben-
with an iron content of 5 of 0.06 mmol/g that was zaldehyde. On the other hand, electron-rich p-me-
measured by ICP-MS analysis.
thoxybenzaldehyde (Table 1, entry 7), p-ACTHNGUTER(NNUG dimethyl)-
1828
asc.wiley-vch.de
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1827 – 1831

Update: An Efficient Synthesis of Poly(ethylene glycol)-Supported Iron(II) Porphyrin
Table 1. Olefination of aldehydes using MeOPEG-immobi-
lized iron(II) porphyrin 5 as catalyst.[a]
Table 2. Recycling experiments for the olefination of benzal-
dehyde using PEG-immobilized iron(II) porphyrin 5.[a]
Entry Substrate
Time [h] Yield [%] E/Z ratio[b]
Run Time
[h]
Isolated yield E/Z
Iron content of pro-
duct[b]
[%]
ratio
1[c]
2
6.0
3.0
12
94
92
99
89
96:4
93:7
96:4
92:8
1
2
3
4
5
6
7
8
3.0
3.0
3.0
3.5
3.5
4.0
4.0
5.0
5.0
6.0
92
89
85
86
91
80
89
85
92
86
93:7
93:7
92:8
92:8
92:8
92:8
92:8
91:9
91:9
91:9
1.7
1.6
<1
1.5
<1
<1
<1
1.6
1.6
1.5
3[c]
4
3.5
5
6
4.0
5.0
87
84
94:6
94:6
9
10
7
8
6.0
1.5
95
93
92:8
93:7
[a]
[b]
Reaction conditions: benzaldehyde (0.5 mmol), ethyl di-
azoacetate (0.6 mmol), Ph3P (0.6 mmol), catalyst
(1 mol%) in toluene (2 mL) at 808C under an N2 atmos-
phere.
Determined by IPC-MS.
5
9[c]
10
3
2.5
2
95
76
90
83
93:7
93:7
96:4
94:6
11[c]
12
1.5
13
24.0
86
91:9
To explore the limits of recyclability and reusability
of the PEG-supported catalyst 5, we chose the olefi-
nation of benzaldehyde as a model reaction. After
complete disappearance of aldehyde by TLC of each
reaction run, the catalyst was precipitated with diethyl
ether, separated by filtration and reused. In recycling
experiments (Table 2), catalyst 5 was used in 10 cycles
with only a small decrease in catalytic efficiency over
the course of the reactions, and >95% of the catalyst
by precipitation (mass balance) could be recycled
after each run. Moreover, the E/Z regioselectivity of
the catalyst remained high throughout the reaction
cycles.
The reaction mechanism for the olefination of alde-
hydes with diazoacetate in the presence of triphenyl-
phospine by using Fe(II) porphyrin has been studied
in detail by Woo et al.[13] They report that iron(II)
complexes catalytically convert diazo esters in the
presence of phosphines to phosphoranes, which in
turn react with aldehydes to yield olefins and phos-
phine oxide. We assume an analogous mechanism for
our catalytic system.
14
12.0
95
93:7
15
16
17
2.5
3.5
73
87
83:17
92:8
7.0
8.0
84
81
86:14
90:10
18
[a]
Reaction conditions: aldehyde (0.5 mmol, 1 equiv.), ethyl
diazoacetate (0.6 mmol, 1.2 equiv.), Ph3P (0.6 mmol,
1.2 equiv.), catalyst 5 (1 mol%), toluene (2 mL) at 808C
under an N2 atmosphere.
[b]
[c]
E/Z ratio determined by 1H NMR.
Taken from ref.[3a]
:
aldehyde (0.94 mmol), Ph3P
(1.04 mmol), ethyl diazoacetate (1.88 mmol, 2 equiv.), 1–
2 mol% Fe(II) (TPP), toluene (3 mL) at ambient temper-
ature under an N2 atmosphere.
In summary, we report the successful synthesis of
a soluble PEG-immobilized iron porphyrin by using
ACHTUNGTRENNUNGaminobenzaldehyde (Table 1, entry 13) and 2,4,6-tri- a copper-catalyzed azide-alkyne [3+2]cycloaddition.
methoxybenzaldehyde (Table 1, entry 14) were found The “click” method offers the advantage of being
to be the least reactive. As a consequence of this re- readily applicable, allowing a good catalyst loading
activity pattern, the selective monoolefination of an and mild reaction conditions for immobilization of
aromatic dialdehyde (Table 1, entry 15) becomes pos- metalloporphyrins. The PEG-immobilized iron por-
sible.
phyrin catalyst 5 affords nearly quantitative conver-
Scheme 2. Olefination of aldehydes with ethyl diazoacetate.
Adv. Synth. Catal. 2012, 354, 1827 – 1831
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1829

Tamilselvi Chinnusamy et al.
UPDATES
phyrin 5 was recovered by filtration and washed with Et2O.
The filtrate was concentrated under reduced pressure and
purified by column chromatography using hexane/ethyl ace-
tate to give pure olefin.
sions, high yields, and high selectivity in the olefina-
tion reaction of aldehydes with ethyl diazoacetate.
The performance of 5 compares well to those of other
immobilized catalysts that are reported for aldehyde
olefination.[14]
Acknowledgements
Experimental Section
This work was supported by the Bavarian Elite Network
NANOCAT.
Synthesis of PEG-Immobilized Iron(II) Porphyrin 5
Synthesis of azido iron(II) porphyrin:
A solution of
FeCl2·4H2O (1.2 mmol, 10 equiv.) in methanol (2 mL) was
added to a solution of azidoporphyrin (0.12 mmol, 1 equiv.)
in chloroform (20 mL) and 2,6-dimethylpyridine (1.2 mmol,
10 equiv.) in the dark. The resulting solution was stirred
under a nitrogen atmosphere for 4 days. After completion,
the solvent was evaporated under reduced pressure and the
resulting residue was dissolved in dichloromethane, washed
with water, brine solution, dried and the solvent was evapo-
rated under reduced pressure. The crude material was puri-
fied on silica (CH2Cl2/MeOH 95:5, Rf =0.4) to afford azido
iron(II) porphyrin; yield: 90%. UV-vis (CH2Cl2): lmax =420,
445, 515, 555 nm; MS (EI-MS): m/z=877.5 (M+); anal.
calcd. for C56H51FeN7·2H2O: C 73.59, H 6.07, N 10.73;
References
[1] a) C. A. McNamara, M. J. Dixon, M. Bradley, Chem.
Rev. 2002, 102, 3275; b) M. Benaglia, A. Puglisi, F.
Cozzi, Chem. Rev. 2003, 103, 3401; c) A. Sakthivel, W.
Sun, G. Raudaschl-Sieber, A. S. T. Chiang, M. Hanzlik,
F. E. Kꢀhn, Catal. Commun. 2006, 7, 302.
[2] a) T. J. Dickerson, N. N. Reed, K. D. Janda, Chem. Rev.
2002, 102, 3325; b) D. E. Bergbreiter, Chem. Rev. 2002,
102, 3345; c) D. J. Gravert, K. D. Janda, Chem. Rev.
1997, 97, 489.
[3] For reviews see: a) B. Meunier, Chem. Rev. 1992, 92,
1411; b) J. P. Collman, X. Zhang, V. J. Lee, E. S. Uffel-
man, J. I. Brauman, Science 1993, 261, 1404; c) P.
Mꢀller, C. Fruit, Chem. Rev. 2003, 103, 2905; d) G. Si-
monneaux, P. Tagliatesta, J. Porphyrins Phthalocyanines
2004, 8, 1166; e) G. Maas, Chem. Soc. Rev. 2004, 33,
183; f) Q.-H. Xia, H.-Q. Ge, C.-P. Ye, Z.-M. Liu, K.-X.
Su, Chem. Rev. 2005, 105, 1603.
[4] a) J.-L. Zhang, C.-M. Che, Org. Lett. 2002, 4, 1911;
b) M. Benaglia, T. Danelli, G. Pozi, Org. Biomol.
Chem. 2003, 1, 454; c) J.-L. Zhang, J.-S. Huang, C.-M.
Che, Chem. Eur. J. 2006, 12, 3020; d) S.-T. Liu, K. V.
Reddy, R.-Y. Lai, Tetrahedron 2007, 63, 1821.
˜
found: C 72.95, H 5.70, N 10.38; IR (neat): n=2924, 2853,
2419, 2122, 2051, 1988, 1735, 1637, 1536 cmÀ1.
Immobilization of azido iron(II) porphyrin 2 to PEG
using CuAAC: A solution of azido iron(II) porphyrin
(0.07 mmol, 1.0 equiv.), CuI (6 mol%), triethylamine (1 mL)
and propargylated MeOPEG5000 4 (0.07 mmol, 1 equiv.) in
dry degassed CH2Cl2 (15 mL) was stirred at room tempera-
ture 18 h under a nitrogen atmosphere. After disappearance
of azido iron(II) porphyrin (confirmed by TLC: CH2Cl2/
MeOH 95:5, Rf =0.4) the reaction mixture was quenched
with 0.1M EDTA solution, the product was extracted with
CH2Cl2 (3ꢃ10 mL). Then the combined organic layer
washed with brine and dried over Na2SO4. After removal of
the solvent, the crude product was precipitated out from di-
ethyl ether. The precipitated reddish brown solid was isolat-
ed by filtration, washed thoroughly with diethyl ether and
dried under vacuum to yield PEG-immobilized Fe(II) por-
phyrin 5. UV-vis (CH2Cl2): lmax =380, 415, 510 nm. The
loading of the iron porphyrin 5 was found to be 0.07 mmol/g
based on the nitrogen content (0.67% N) as determined by
elemental analysis and 0.06 mmol/g based on ICP-MS analy-
[5] a) C. W. Tornøe, M. Meldal, in: American Peptide Sym-
posium, (Eds.: M. Lebl, R. A. Houghten), American
Peptide Society and Kluwer Academic Publishers, San
Diego, CA, 2001, p 263; b) V. V. Rostovtsev, L. C.
Green, V. V. Fokin, K. B. Sharpless, Angew. Chem.
2002, 114, 2708; Angew. Chem. Int. Ed. 2002, 41, 2596;
c) C. W. Tornøe, C. Christensen, M. Meldal, J. Org.
Chem. 2002, 67, 3057.
[6] R. Huisgen, Pure Appl. Chem. 1989, 61, 613.
˜
sis of iron. IR (neat): n=2886, 1596, 1467, 1440, 1340, 1279,
[7] a) E. M. Ryu, Y. Zhao, Org. Lett. 2005, 7, 1035; H. C.
Kolb, K. B. Sharpless, Drug Discovery Today 2003, 8,
1128; b) P. Wu, M. Malkoch, J. N. Hunt, R. Vestberg,
E. Kaltgrad, M. G. Finn, V. V. Fokin, K. B. Sharpless,
C. J. Hawker, Chem. Commun. 2005, 5775; c) A. Gis-
sibl, M. G. Finn, O. Reiser, Org. Lett. 2005, 7, 2325;
d) A. Gheorghe, A. Matsuno, O. Reiser, Adv. Synth.
Catal. 2006, 348, 1016; e) A. Gheorghe, E. C. Yanez, J.
Horn, W. Bannwarth, B. Narsaiah, O. Reiser, Synlett
2006, 2767; f) D. Font, C. Jimeno, M. A. Pericꢄs, Org.
Lett. 2006, 8, 4653; g) E. Fernandez-Megia, J. Correa, I.
Rodriguez-Meizoso, R. Riguera, Macromolecules 2006,
39, 2113; h) D. Font, A. Bastero, S. Sayalero, C.
Jimeno, M. A. Pericꢄs, Org. Lett. 2007, 9, 1943; i) A.
Gissibl, C. Padie, M. Hager, F. Jaroschik, R. Rasappan,
E. Cuevas-Yanez, C.-O. Turrin, A.-M. Caminade, J.-P.
1241, 1174, 1149, 1099, 1069, 995, 962, 842, 804, 748, 702,
660 cmÀ1.
General Experimental Procedure for Olefination of
Aldehydes
Into a 10-mL Schlenk tube placed in a preheated oil bath at
808C were added aldehyde (0.5 mmol), ethyl diazoacetate
(0.6 mmol), triphenylphosphine (0.6 mmol) and catalyst 5
(1 mol%) in toluene (1 mL) under a nitrogen atmosphere.
The homogeneous mixture was stirred for the period indi-
cated in Table 1. After completion of the reaction, the re-
sulting mixture was cooled to room temperature and con-
centrated under reduced pressure. The residue was treated
with diethyl ether, the precipitated PEG-supported iron por-
1830
asc.wiley-vch.de
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1827 – 1831

Update: An Efficient Synthesis of Poly(ethylene glycol)-Supported Iron(II) Porphyrin
Majoral, O. Reiser, Org. Lett. 2007, 9, 2895; j) A. Bas-
tero, D. Font, M. A. Pericas, J. Org. Chem. 2007, 72,
2460; k) E. Alza, X. C. Cambeiro, C. Jimeno, M. A.
Pericꢄs, Org. Lett. 2007, 9, 3717; l) D. Font, S. Sayalero,
A. Bastero, C. Jimeno, M. A. Pericꢄs, Org. Lett. 2008,
10, 337; m) E. Alza, C. Rodriguez-Escrich, S. Sayalero,
A. Bastero, M. A. Pericꢄs, Chem. Eur. J. 2009, 15,
10167; n) D. Popa, R. Marcos, S. Sayalero, A. Vidal-
Ferran, M. A. Pericꢄs, Adv. Synth. Catal. 2009, 351,
1539; o) A. Schꢁtz, M. Hager, O. Reiser, Adv. Funct.
Mater. 2009, 19, 2109; p) A. Schꢁtz, T. R. Long, R. N.
Grass, W. J. Stark, P. R. Hanson, O. Reiser, Adv. Funct.
Mater. 2010, 20, 4323; q) E. Alza, S. Sayalero, X. C.
Cambeiro, R. Martꢅn-Rapffln, P. O. Miranda, M. A.
Pericꢄs, Synlett 2011, 464.
of 4 – the reported catalyses were therefore performed
by a mixture of MeOPEG/azido-Fe(II) TPP that was
nevertheless efficiently recovered by precipitation – we
decided to retract our original report: S. Jain, J. K.
¨
Joseph, F. E. Kuhn, O. Reiser, Adv. Synth. Catal. 2011,
353, 1391.
[10] M. Severac, L. L. Pleux, A. Scarpaci, E. Blart, F.
Odobel, Tetrahedron Lett. 2007, 48, 6518.
[11] a) V. Rodionov, H. Gao, S. Scroggins, D. A. Unruh, A.-
J. Avestro, J. M. J. FrØchet, J. Am. Chem. Soc. 2010,
132, 2570; b) G. Ru¯ta, C. Gediminas, M. Ric?ardas,
Chemija 2009, 20, 241.
[12] The theoretical loading of complex 2 to MeOPEG5000 is
approximately 0.17 mmol/g.
[13] a) G. A. Mirafzal, G. Cheng, L. K. Woo, J. Am. Chem.
Soc. 2002, 124, 176; b) G. Cheng, G. A. Mirafzal, L. K.
Woo, Organometallics 2003, 22, 1468.
[14] a) S. Syukri, W. Sun, F. E. Kꢀhn, Tetrahedron Lett.
2007, 48, 1613; b) W. Sun, F. E. Kꢀhn, Tetrahedron Lett.
2004, 45, 7415.
[8] a) X.-Y. Wang, A. Kimyonok, M. Weck, Chem.
Commun. 2006, 3933; b) S. Jain, O. Reiser,
ChemSusChem 2008, 1, 534; A. Schꢁtz, R. N. Grass, Q.
Kainz, W. J. Stark, O. Reiser, Chem. Mater. 2010, 22,
305.
¨
[9] S. Jain, J. K. Joseph, F. E. Kuhn, O. Reiser, Adv. Synth.
Catal. 2009, 351, 230. Due to the failure of the synthesis
Adv. Synth. Catal. 2012, 354, 1827 – 1831
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1831