The oxidation of Ni(ii) N-confused porphyrins (NCPs) with azo radical initiators and an unexpected intramolecular nucleophilic substitution reaction via a proposed Ni(iii) NCP intermediate

Article abstract of DOI:10.1039/b904615a

The oxidation of Ni(ii) N-confused porphyrins (NCPs) with azo radical initiators resulted in an unexpected intramolecular nucleophilic substitution reaction via a proposed Ni(iii) NCP intermediate, which could be detected by HRMS.

Full text of DOI:10.1039/b904615a

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The oxidation of Ni(II) N-confused porphyrins (NCPs) with azo radical
initiators and an unexpected intramolecular nucleophilic substitution
reaction via a proposed Ni(III) NCP intermediatew
Hua-Wei Jiang,a Qing-Yun Chen,a Ji-Chang Xiao*a and Yu-Cheng Gub
Received (in Cambridge, UK) 5th March 2009, Accepted 27th April 2009
First published as an Advance Article on the web 15th May 2009
DOI: 10.1039/b904615a
The oxidation of Ni(II) N-confused porphyrins (NCPs) with azo
radical initiators resulted in an unexpected intramolecular
nucleophilic substitution reaction via a proposed Ni(III) NCP
intermediate, which could be detected by HRMS.
Ni(III) species are very rare and usually show low stability,3
and to the best of our knowledge, Ni(III) normal porphyrins
have never been isolated and characterized by single crystal
X-ray diffraction analysis. The stability of Ni(III) porphyrins is
related to many factors, among which the nature of the
porphyrin ligand itself is important. It has been shown that
Ni(III) N-confused porphyrins [Ni(III) NCPs] prepared by
oxidation or metathesis are stable enough for electron
The organometallic chemistry of nickel, especially that of
Ni(III), has attracted great interest in recent years.1–13 Organic
Ni(III) species are key intermediates in many chemical
reactions8c,9 and the formation of a Ni(III)-s bond is also
of great biological importance in some enzyme catalyzed
reactions. For example, the F430 Ni(III)–methyl species plays
an important role in the last chemical step of methane formation
catalyzed by methylcoenzyme M reductase (MCR).1,6 Ni(III)
complexes have also been proposed as intermediates in the
enzyme cycles involving both acetyl coenzyme A synthase2 and
carbon monoxide dehydrogenase.5b,14 Our understanding of
the way in which nickel functions in these enzymes is usually
limited to that derived from spectroscopic methods and
calculations,3,5 and the detailed role of the nickel center is
not clear at present. Synthetic modeling of nickel biosites is
another promising way to investigate the precise function of
the nickel ion in these biological processes. Ni(III)–C s-bonded
intermediates, synthesized by the reaction of a methyl radical
with macrocyclic complexes Ni(II)L (L = cyclam derivatives),
were studied by pulse radiolysis16,17 and flash photolysis.18
Further kinetic and thermodynamic studies demonstrated that
the methyl radical formally oxidizes these Ni(II)L complexes in
an equilibrium process with a relatively fast forward rate.10
These results provide further indirect support for the proposal
that Ni(III)–CH3 species act as crucial intermediates in
enzymes like carbon monoxide dehydrogenases and acetyl
coenzyme A synthase.14,15
2
paramagnetic resonance (EPR) and H NMR studies, which
means that N-confused porphyrins (NCPs) do stabilize Ni(III)
to some extent.20,21
N-Confused porphyrin (NCP), which was first reported
independently by Furuta et al. and by Latos-Grazynski et al.
´
˙
in 1994,22 is a porphyrin isomer in which one of the pyrrole
rings is inverted. The special NNNC inner core often
stabilizes atypical oxidation states or unusual coordination
geometries.9,23 The chemistry of NCP complexes with metals
of biological relevance has been explored with the aim of
generating heme-model complexes.24 We have become very
interested in NCP chemistry, and recently reported the
synthesis and reactions of the first fluoroalkylated Ni(II)
NCPs.25 Based on our interest in the oxidative chemistry of
Ni(II) porphyrins and the recognition that NCPs can stabilize
Ni(III), we have studied the oxidation of Ni(II) NCPs with azo
radical initiators. We found that inner 21-C-substituted Ni(II)
NCPs were obtained instead of the expected Ni(III) species.
However, we propose that Ni(III) NCP intermediates were
involved in the formation of the observed products. Herein, we
present our results.
Treatment of Ni(II) N-confused tetratolylporphyrin Ni2
with AIBN in freshly distilled anhydrous toluene at 70 1C
for 4 h gave, after flash chromatography, a purple compound
Ni2a (Scheme 1). The intense absorption at 434 nm (Soret
band) and the weak absorption at 716 nm (Q band) observed
in the UV/Vis spectrum indicated that the porphyrin-like
The porphyrin-like skeleton of F430 in MCR inspired us to
search for porphyrinoid ligands that could stabilize Ni(III)
species. It is known that Ni(III) porphyrins can be obtained
by the oxidation of Ni(II) porphyrins (if the oxidation takes
place on the nickel),19 a fact that aroused our interest in the
study of the oxidative chemistry of Ni(II) porphyrins. Organic
a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, Shanghai 200032, P. R. China.
E-mail: jchxiao@mail.sioc.ac.cn; Fax: (+86) 21-6416 6128
b Syngenta, Jealott’s Hill International Research Centre, Bracknell,
Berkshire, UK RG42 6EY
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization data. CCDC 715233. For
crystallographic data in CIF or other electronic format, see DOI:
10.1039/b904615a
Scheme 1 The reaction of Ni2 and AIBN.
ꢀc
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3732 | Chem. Commun., 2009, 3732–3734

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1
skeleton had been preserved. The H NMR and mass spectra
Table 2 The reactions of the Ni1, Ni2 with azo radical initiators
indicated that the product might be the 21-CN substituted Ni(II)
NCP, and further comparisons of these data with those of an
authentic 21-CN substituted Ni(II) NCP prepared according to
the reported procedure26 confirmed our speculation.
The reaction conditions were optimized using Ni1 as a
model substrate. It was found that the amount of AIBN and
the reaction temperature have a significant effect on the yield;
4 equiv. of AIBN should be used to facilitate complete
conversion of Ni1 and 60 1C is a suitable temperature for
this reaction. A much longer reaction time is required at
lower temperatures (Table 1, entries 1 and 2), while higher
temperatures didn’t increase the yield of Ni1a (Table 1, entry 4).
Under the optimal reaction conditions, we investigated the
reaction of the Ni(II) NCPs Ni1, Ni2 with azo radical initiators,
namely, AIBN, dimethyl 2,20-azobis(2-methylpropionate) and
diethyl 2,20-azobis(2-methylpropionate) (Table 2). The desired
inner-substituted Ni(II) NCPs (Ni1a–Ni1c, Ni2a–Ni2c) were
obtained for each substrate in yields of B40% in each case.
Most of the starting Ni(II) NCPs (B60%) decomposed under
this reaction condition. To the best of our knowledge, these are
the first examples of azo radical initiators being used for
the introduction of cyano or alkoxycarbonyl substituents to
organic compounds.
Entry
R1
R2
Product
Yielda (%)
1
2
3
4
5
6
H
H
H
CH3
CH3
CH3
CN
Ni1a
Ni1b
Ni1c
Ni2a
Ni2b
Ni2c
45
38
37
42
40
39
COOCH3
COOC2H5
CN
COOCH3
COOC2H5
a
Isolated yield.
To understand the reaction mechanism, some inhibition
experiments were carried out. The addition of an electron
scavenger, 1,4-dinitrobenzene (20 mol%), or a free radical
inhibitor, hydroquinone (20 mol%), to the mixture of Ni2
and AIBN suppressed the reaction, and no products were
formed over a period of 4 h. These results imply that the
generation of the radical CN(CH3)2Cꢁ is essential for the
reaction and excludes
a simple nucleophilic substitution
mechanism. We propose a mechanism involving the Ni(III)–alkyl
species shown in Scheme 2 (which is shown for dimethyl
2,20-azobis(2-methylpropionate) as an example). Firstly, the
(COOCH3)(CH3)2Cꢁ radical oxidizes Ni(II) NCP to form an
NCP Ni(III)–alkyl species, the intermediate A. Subsequent
intramolecular nucleophilic attack results in the formation of
a four-membered ring, intermediate B. The opening of the
four-membered ring and cleavage of the Ni(III)–alkyl s-bond
gives the final product.
Scheme 2 Proposed mechanism.
EPR spectroscopy. For that reason, we tried to identify the
Ni(III) intermediates by mass spectrometry, which is a useful tool
for the characterization of some active intermediates. In situ low
resolution mass spectroscopic analysis of the reaction mixture of
Ni2 and b gave a m/z signal at 827.3 (Scheme 3), and further
analysis by high resolution mass spectroscopy (HRMS) gave a
m/z signal at 827.2880, which is in agreement with the calculated
m/z of 827.28905 for the proposed Ni(III) intermediate (see the
ESIw). Although this result strongly supports the intermediacy
of the proposed Ni(III) species, we cannot completely exclude the
p-radical cation mechanism at present.27
2
According to the reported EPR and H NMR studies, the
oxidation of Ni(II) NCP takes place on the nickel atom rather
than the NCP ring.20 This means that only Ni(III) NCP was
formed in the oxidation process and no p-cation radicals were
produced. So, we speculate that the Ni(III) intermediate A was
generated in the first step of the reaction. However, as a result of
the instability of the Ni(III) NCP species, the intermediates could
not be isolated. The high concentration of alkyl radical makes it
difficult to detect the small amount of Ni(III) intermediates by
Demetallation of Ni1a–Ni1c proceeded smoothly in the
presence of concentrated hydrochloric acid, leading to the
corresponding free base inner-substituted NCPs 1a–1c in good
yields. The structure of 1b was confirmed by single crystal
X-ray diffraction analysis (Fig. 1).z
Table 1 The reaction of Ni1 and AIBN at different temperatures
Entry Temperature/1C Time/h Conversion (%) Yielda (%)
1
2
3
4
20
40
60
70
108
36
4
o5
100
100
100
o5
41
45
42
In conclusion, we have shown that Ni(II) NCPs, upon
treatment with certain azo radical initiators, undergo an
unexpected cyanation or alkoxycarbonylation at the inner
4
a
Isolated yield of compound Ni1a.
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 3732–3734 | 3733

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wR2 = 0.2085 (I 4 2s(I)); R1 = 0.1225, wR2 = 0.2336 (all data).
Reflections collected/unique: 20843/7564 (Rint = 0.0692).
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Notes and references
z Crystal data for 1bꢂCH2Cl2 (CCDC 715233): C47H34Cl2N4O2,
M
=
757.68, monoclinic,
a
=
11.6814(10),
b
=
17.6688(15),
c = 19.2955(17) A, b = 104.487(2)1, V = 3855.9(6) A3, T = 293(2) K,
space group P21/c, Z = 4, m(Mo-Ka) = 0.214 mmꢃ1, R1 = 0.0740,
ꢀc
This journal is The Royal Society of Chemistry 2009
3734 | Chem. Commun., 2009, 3732–3734