Synthesis and reactions of the first fluoroalkylated Ni(II) N-confused porphyrins

Article abstract of DOI:10.1039/b811831k

The first fluoroalkylated Ni(II) N-confused porphyrins were synthesized with high regioselectivity and its further alkylation was studied. The Royal Society of Chemistry.

Full text of DOI:10.1039/b811831k

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Synthesis and reactions of the first fluoroalkylated Ni(II) N-confused
porphyrinsw
Hua-Wei Jiang,a Qing-Yun Chen,a Ji-Chang Xiao*a and Yu-Cheng Gub
Received (in Cambridge, UK) 10th July 2008, Accepted 19th August 2008
First published as an Advance Article on the web 22nd September 2008
DOI: 10.1039/b811831k
The first fluoroalkylated Ni(II) N-confused porphyrins were
synthesized with high regioselectivity and its further alkylation
was studied.
unique structure and properties, we have extended this direct
fluoroalkylation method to NCPs. Herein, we report the first
fluoroalkylation of Ni(II) NCPs and their subsequent reactions.
Treatment of the Ni(II) N-confused tetraphenylporphyrin
(Ni1) with I(CF2)4Cl in the presence of copper powder in
DMSO at 100 1C for 40–60 min gave, after filtration, extrac-
tion and flash chromatography, a purple compound. The
intense absorption at 435 nm (Soret band) and the weak
absorptions at 567, 610 and 781 nm (Q band) observed in
the UV/Vis spectrum indicated that the porphyrin-like skele-
ton had been preserved. Furthermore, the 19F NMR and MS
results showed that the fluoroalkyl group had successfully
been introduced into the Ni(II) NCP. The AB pattern signals
appearing at d ꢀ93.69 and ꢀ96.07 ppm (JAB = 269.8 Hz) in
the 19F NMR spectrum suggested that the fluoroalkyl group
was attached to a chiral center. The chemical shift of C(3)H at
d 9.78 ppm and of the six b-pyrrole protons at d 8.40–8.65 ppm
was in good agreement with the 21-C substituted Ni(II) NCPs
(see ESIw),6,19 which implied that the fluoroalkyl group had
been introduced at the inner carbon of compound Ni1
(Scheme 1).
The chemistry of N-confused porphyrins (NCPs) has attracted the
attention of many chemists since the first synthesis was reported
independently by Furuta and by Latos-Grazyn
´
ski in 1994.1 NCPs
˙
have a number of applications in the area of supermolecular self-
assembly and coordination chemistry, because of their versatile
coordination modes and ability to stabilize some rare high oxida-
tion states of metal ions.2 The biologically relevant metal che-
mistry of N-confused porphyrins has been explored with the aim
of generating heme-model complexes.3 Further applications of
NCPs in catalytic reactions revealed that they can outperform
porphyrins and corroles in some circumstances.4 Considerable
efforts have been made to modify the structures of NCPs by, for
example, halogenation,5 nitration,5 cyanation,6 oxygenation,7
internal fusion,5,8 Diels–Alder reaction,9 and N-alkylation.10
These modifications have led to a much deeper understanding
of the reactivities of NCPs and of their differences from other
porphyrin analogues.
The structure of Ni1b was confirmed by single crystal X-ray
diffraction analysis.z The results showed that the fluoroalkyl
group was attached to the inner 21-carbon rather than to one of
the peripheral carbon atoms (Fig. 1). This is in contrast to the
alkylation of Ni1, which gave low yields of a mixture of inner
21-carbon and inverted 2-nitrogen alkylated products.19,20 Good
selectivity and yield can be achieved in the fluoroalkylation of
the Ni(II) NCP Ni1. The C(21)-Ni distance (2.033(7) A) in Ni1b
is slightly longer than those (2.005(6), 2.019(4), 2.018(3) A)
observed in the inner C-substituted Ni(II) NCPs.6,19 However,
taking the deviation into account, it still doesn’t exceed the
upper limit of C–Ni bond length (2.02(2) A).21 So there is a
s-bond between C(21) and Ni atom, suggesting that the C(21)
adopts an sp3 hybridization.
The introduction of fluorine or fluoroalkyl groups into the
porphyrin macrocycle has profound effects on its physical and
chemical properties.11,12 In this context, we have developed
several efficient methods for synthesizing fluorinated porphyrins,
using, for example, a sulfinatodehalogenation reaction,13 or
copper- or palladium-catalyzed fluoroalkylation.14,15 These
direct fluoroalkylation methods have proved to be important
for the preparation of certain fluoroalkylated porphyrins which
are very difficult to obtain by the condensation of fluoroalkyl
pyrroles and/or fluoroalkyl aldehydes.
We have synthesized a variety of fluoroalkylated porphyrins
and studied their properties.16,17 After the introduction of four
trifluoromethyl groups into meso-tetraphenylporphyrin, we
successfully isolated and thoroughly characterized the challen-
ging 20 p-electron nonaromatic isophlorin which was referred
to for the first time by Woodward during the synthesis of
chlorophyll about half a century ago.18 Considering their
a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin
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 689873. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/b811831k
Scheme 1 Synthesis of inner 21-C fluoroalkylated NCP ( Ni1b).
Chem. Commun., 2008, 5435–5437 | 5435
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effect on the yield. A large excess of I(CF2)4Cl (30 equiv.)
should be used to facilitate complete conversion of Ni1. It was
found that 100 1C is a suitable temperature for this reaction.
Higher temperatures increase the decomposition of the Ni1,
while a much longer reaction time is required at lower
temperatures.
Under the optimal reaction conditions, we investigated the
fluoroalkylation of other NCPs containing electron-donating
or electron-withdrawing substituents on the benzene rings
(Table 1).
The desired fluoroalkylated NiNCPs were obtained for each
substrate. The yields of Ni3 with a chloro group at the
para-position on the phenyl ring (entries 10–12) were much
lower than those of Ni2 with a corresponding methyl group
(entries 6–8). It can therefore be inferred that the substituents on
the phenyl ring influence electrophilic fluoroalkylation through
their effects on the electron density of the conjugated p system of
NiNCPs. The yields became rather low when I(CF2)2Cl was
used as the fluoroalkylating reagent, even with prolonged
reaction times and a large excess of I(CF2)2Cl (100 equiv.)
(entries 1, 5, 9). The low boiling point of I(CF2)2Cl and the fact
that it is readily converted into tetrafluoroethylene under these
reaction conditions may contribute to the decrease in yield.
To understand the reaction mechanism, some inhibition
experiments were carried out. The addition of an electron
scavenger, p-dinitrobenzene (20 mol%), or a free radical
inhibitor, hydroquinone (20 mol%), to the reaction mixture
of Ni1 and I(CF2)2Cl had no effect on the reaction. These
negative results implied the existence of fluoroalkylcoppers as
reaction intermediates instead of fluoroalkyl radicals. This led
us to propose that the reaction mechanism may involve the
addition of a fluoroalkylcopper species across the CQC
double bond to form a new unstable copper species on the
Table 1
Fig. 1 Molecular structure of compound Ni1b with 30% thermal
ellipsoids. The solvent CH2Cl2 was omitted for clarity: (a) top view;
(b) side view.
As a result of the change in hybridization patterns, the
p-delocalization of the macrocycle must take an outer path
C(1)–N(2)–C(3)–C(4) in the confused pyrrole moiety. The
introduction of a fluoroalkyl group to the inner core distorts
the planarity of the porphyrin macrocycle. The dihedral angles
(1) between the planes of the pyrrole rings and that defined by
N(22)N(23)N(24) are as follows: C(21) 40.14(30), N(22)
ꢀ11.81(44), N(23) 8.60(49), N(24) ꢀ14.33(43). These crystal
structure features are very similar to those of the 21-C
methylated Ni(II) NCP19 and the inner C-cyanated Ni(II)
NCPs.6 The UV/Vis spectrum of Ni1b closely resembles that
of 21-C methylated Ni(II) NCPs,19 because of their structural
similarity. The intense absorption at 435 nm (Soret band) and
the weaker ones in the visible region (Q-band) (See ESIw) are
the typical characteristics of metalloporphyrins.
Entry
R
RfI
Product
Yieldb (%)
1
2
3
4
5
6
7
8
9
H
H
H
H
CH3
CH3
CH3
CH3
Cl
Cl
Cl
Cl
I(CF2)2Cla
I(CF2)4Cl
I(CF2)6Cl
IC6F13
Ni1a
Ni1b
Ni1c
Ni1d
Ni2a
Ni2b
Ni2c
Ni2d
Ni3a
Ni3b
Ni3c
Ni3d
37
88
78
78
32
92
91
90
33
62
56
58
I(CF2)2Cla
I(CF2)4Cl
I(CF2)6Cl
IC6F13
I(CF2)2Cla
I(CF2)4Cl
I(CF2)6Cl
IC6F13
10
11
12
a
The reaction conditions were optimized using Ni1 and
I(CF2)4Cl as model substrates. It was found that the amount
of I(CF2)4Cl and the reaction temperature have a significant
b
100 equiv. was used. Isolated yield.
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Notes and references
z Crystal data for Ni1b: C49H29Cl3F8N4Ni,
M
=
990.82,
ꢀ
triclinic, space group P1, a = 11.3724(16), b = 14.584(2), c =
14.714(2) A, a = 63.602(3), b = 77.491(3), g = 85.060(3)1, V =
2133.8(5) A3, T = 293(2) K, Z = 2, m(Mo-Ka) = 0.719 mmꢀ1
,
R1 = 0.0906, wR2 = 0.2163 (I 4 2s(I)); R1 = 0.1792, wR2 = 0.2551
(all data). Reflections collected/unique: 11252/7808 (Rint = 0.0952).
Disorders at the fluoroalkyl chain and the solvent CH2Cl2 were
found.
1 (a) P. J. Chmielewski, L. Latos-Grazyn
´
ski, K. Rachlewicz and T.
G"owiak, Angew. Chem., 1994, 104, 805; P. J. Chmielewski, L.
Latos-Grazynski, K. Rachlewicz and T. G"owiak, Angew. Chem.,
˙
´
˙
Scheme 2 Reactions of 21-C fluoroalkylated Ni(II) NCPs with methyl
iodide.
Int. Ed. Engl., 1994, 33, 779; (b) H. Furuta, T. Asano and T.
Ogawa, J. Am. Chem. Soc., 1994, 116, 767.
2 (a) H. Furuta, H. Maeda, T. Ogawa and A. Osuka, Chem.
Commun., 2002, 1795; (b) J. D. Harvey and C. J. Ziegler, Coord.
Chem. Rev., 2003, 247, 1; (c) A. Ghosh, Angew. Chem., Int. Ed.,
2004, 43, 1918; (d) A. Srinivasan and H. Furuta, Acc. Chem. Res.,
2005, 38, 10; (e) H. Maeda and H. Furuta, Pure Appl. Chem., 2006,
confused pyrrole ring. This is similar to our previous report on
the fluoroalkylation of porphyrins.17 The new unstable copper
species breaks down to a radical and subsequently loses a
hydrogen atom to yield the fluoroalkylated NCPs. This
mechanism is quite different from that proposed for methyla-
tion, in which Ni(IV) or Ni(III) species might be involved in the
transition state.19 The mechanism based on the property of
CQC double bond may open up new route for the modifica-
tion of Ni(II) NCPs.
78, 29; (f) P. J. Chmielewski and L. Latos-Grazynski, Coord. Chem.
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Rev., 2005, 249, 2510.
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3 J. D. Harvey and C. J. Ziegler, J. Inorg. Biochem., 2006, 100, 869.
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J. Am. Chem. Soc., 1999, 121, 2945; (b) H. Furuta, H. Maeda, T.
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M. J. Taschner and C. J. Ziegler, J. Org. Chem., 2006, 71,
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To explore the possibility for further functionalization of the
fluoroalkylated NiNCPs, methyl iodide was chosen as an
alkylating reagent. It was found that reactions between 21-C
fluoroalkylated Ni(II) NCPs and methyl iodide proceeded
smoothly, giving the N-methylated NiNCPs in good yields
(Scheme 2). The structures of these N-methylated products
were assigned by MS and UV/Vis spectroscopy, as well as
elemental analysis (see ESIw). The UV/Vis absorption spectra of
these paramagnetic organometallic Ni(II) complexes,
2-aza-2-methyl-21-fluoroalkyl-5,10,15,20-tetraphenyl-21-carba-
porphyrinatonickel(II) iodides, are quite similar to that of
2-aza-2,
21-dimethyl-5,10,15,20-tetraphenyl-21-carbapor-
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phyrinatonickel(II) iodide.19
In conclusion, we have developed for the first time an
effective route for the synthesis of fluoroalkylated N-confused
porphyrins. The fluoroalkyl group was introduced specifically
onto the inner carbon of the porphyrin ring system. No
regioisomeric products were found. The structure was
determined by single-crystal X-ray diffraction. Subsequent
methylation reactions proceeded smoothly under mild
conditions. Further studies on the properties and applications
of fluoroalkylated N-confused porphyrins are now under way.
We thank the Chinese Academy of Sciences (Hundreds of
Talents Program), the National Science Foundation
(20772147) and Syngenta Ltd for the financial support. We
thank Dr John Clough of Syngenta Jealott’s Hill International
Research Centre for his suggestions and proofreading.
19 P. J. Chmielewski, L. Latos-Grazynski and T. G"owiak, J. Am.
´
˙
Chem. Soc., 1996, 118, 5690.
20 I. Schmidt and P. J. Chmielewski, Inorg. Chem., 2003, 42, 5579.
21 L. Sacconi, P. Dapporto, P. Stoppioni, P. Innocenti and C.
Benneli, Inorg. Chem., 1977, 16, 1669.
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