Direct meso-alkynylation of porphyrins doubly assisted by pyridyl coordination

Article abstract of DOI:10.1021/ol301005b

Direct meso-alkynylation of β,β′-dipyridylporphyrin with various alkynyllithium reagents has been achieved, in which the β,β′-dipyridyl groups play an important role in facilitating the nucleophilic addition of the reagents through double coordination. This method enabled the synthesis of a meso-ethynylene-bridged diporphyrin.

Full text of DOI:10.1021/ol301005b

ORGANIC
LETTERS
2012
Vol. 14, No. 11
2778–2781
Direct meso-Alkynylation of Porphyrins
Doubly Assisted by Pyridyl Coordination
Shoma Anabuki,† Sumito Tokuji,† Naoki Aratani,*,†,‡ and Atsuhiro Osuka*,†
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku,
Kyoto 606-8502, Japan, and PRESTO, Japan Science and Technology Agency, Japan
aratani@kuchem.kyoto-u.ac.jp; osuka@kuchem.kyoto-u.ac.jp
Received April 17, 2012
ABSTRACT
Direct meso-alkynylation of β,β0-dipyridylporphyrin with various alkynyllithium reagents has been achieved, in which the β,β0-dipyridyl groups
play an important role in facilitating the nucleophilic addition of the reagents through double coordination. This method enabled the synthesis of a
meso-ethynylene-bridged diporphyrin.
Meso-alkynylated porphyrins have often served as an
important component of conjugated porphyrin arrays1ꢀ5
since meso-alkynyl substituents provide substantial elec-
tronic perturbation to porphyrins and work as an effective
mediator of electronic communication. In addition, ethy-
nyl and 1,3-butadiynyl moieties are convenient and effec-
tive construction motifs for covalent connections. So far,
these meso-alkynylated porphyrins have been prepared by
functional group transformations either from meso-formyl
porphyrins3 or meso-halogenated porphyrins,1 or alterna-
tively by condensations of alkynal with suitable pyrrolic
precursors.2 Direct meso-alkynylations of porphyrins
would be desirable from the viewpoint of reaction
efficiency but remain unexplored to date, to the best of
our knowledge.
As an effective synthetic method, Senge et al. have
developed the meso-functionalization reaction of porphyrins
that consists of nucleophilic addition of aryl or alkyllithium
reagents, protonation with water to form meso-substituted
phlorins, and final oxidation with 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ) to furnish meso-
substituted porphyrins.6 This reaction is applicable to a
wide range of aryl and alkyllithium reagents but not to
alkynyllithium reagents.
† Kyoto University.
‡ PRESTO.
(1) (a) Lin, V. S.-Y.; DiMagno, S. G.; Therien, M. J. Science 1994,
264, 1105. (b) Lin, V. S.-Y.; Therien, M. J. Chem.;Eur. J. 1995, 1, 645.
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Perkin Trans. 1 1978, 366. (b) Atefi, F.; Arnold, D. P. J. Porphyrins
Phthlocyanines 2008, 12, 801. (c) Arnold, D. P.; Nitschinsk, L. J.
Tetrahedron Lett. 1993, 34, 693.
(4) (a) Proess, G.; Pankhert, D.; Hevesi, L. Tetrahedron Lett. 1992,
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(5) (a) Sugiura, K.; Fujimoto, Y.; Sakata, Y. Chem. Commun. 2000,
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Sugiura, K.; Miyasaka, H.; Tanaka, H.; Kawai, T.; Sugimoto, M.;
Yamashita, M. Chem. Lett. 2004, 33, 578.
Figure 1. 2,18-Di-(2-pyridyl)porphyrin and its pincer complexes.
r
10.1021/ol301005b
Published on Web 05/17/2012
2012 American Chemical Society

In the course of our own studies on porphyrin pincer
complexes,7ꢀ10 we prepared phenylplatinum(II) pincer
complex 2 and (phenylethynyl)platinum(II) pincer com-
plex 3 from 2,18-di-(2-pyridyl)-5,10,15-tris(3,5-di-tert-butyl-
phenyl)-substituted Ni(II)porphyrin (1Ni)7 and found that
these pincer complexes gave different products upon oxi-
dation with iodine (Figure 1). While 2 gave an expected
meso-phenylated porphyrin probably via simple reductive
elimination,9 the oxidation products obtained from 3
commonly had unique structures bearing a CꢀC bond at
the meso position and Pt(II) metal remained even after
reductive elimination because of the strong coordination
with the two pyridyl moieties.10 Curiously, in the presence
of an excess amount of phenylethynyl iodide, 3 underwent
double phenylethynylation to provide a meso-spiro-cyclo-
pentadienyl isoporphyrin.10 We thought that porphyrin
1Ni might be a nice substrate for direct nucleophilic
alkynylation at the unsubstituted meso position owing to
coordination assistance by the neighboring 2-pyridyl sub-
stituents. In this paper, we disclose a facile, direct meso-
alkynylation reaction of 1Ni with alkynyllithium reagents
(Scheme 1).
in THF, which was followed by the addition of water and
oxidation with DDQ. Gratifyingly, this reaction smoothly
proceeded to provide β,β0-dipyridyl meso-phenylethynyl-
porphyrin 4a as a sole product in 86% yield (Scheme 1).
The structure of 4a is fully consistent with the spectros-
copic data. High-resolution electrosprayꢀionization time-
of-flight (HR-ESI-TOF) mass spectral analysis detected
the parent ion peak of 4a at m/z = 1185.6017 (calcd for
1
C80H83N6Ni = 1185.6027 [M þ H]þ). The H NMR
spectrum of 4a exhibits the ortho-protons of the phenyl
group at δ = 6.55ppm, which are slightly upfield shifted as
a result of the ring current of the pyridyl groups. Slow
vapor diffusion of acetonitrile to a dichloroethane solution
of 4a gave nice crystals suitable for X-ray diffraction
analysis. The crystal structure of 4a revealed a meso-
phenylethynylated skeleton unambiguously, in which the
porphyrin core is distorted into a saddle conformation and
the phenylethynyl group is deviated from the porphyrin
mean plane due to the steric hindrance by the pyridyl groups
(Figure 2).11 In addition, the 2-pyridyl substituents take a
conformation with their pyridyl nitrogen atom oppositely
oriented with regard to the meso-alkynyl substituent.
Scheme 1. Synthesis of meso-Alkynyl Porphyrinsa
a Ar = 3,5-di-tert-butylphenyl. Reaction conditions: 1Ni (46.0 μmol),
lithium reagent (5.0 equiv), DDQ (1.5 equiv), THF (4 mL), 0 °C, 3 h. b12 h.
First, we examined the reaction of 1Ni with phenylethynyl-
lithium byfollowing Senge’sprotocol.6 Namely, porphyrin
1Ni was treated with phenylethynyllithium at 0 °C for 3 h
(6) (a) Kalisch, W. W.; Senge, M. O. Angew. Chem., Int. Ed. 1998, 37,
1107. (b) Senge, M. O.; Feng, X. Tetrahedron Lett. 1999, 40, 4165.
(7) (a) Yamaguchi, S.; Katoh, T.; Shinokubo, H.; Osuka, A. J. Am.
Chem. Soc. 2007, 129, 6392. (b) Yamamoto, J.; Shimizu, T.; Yamaguchi,
S.; Aratani, N.; Shinokubo, H.; Osuka, A. J. Porphyrins Phthalocyanines
2011, 15, 534. (c) Yamaguchi, S.; Katoh, T.; Shinokubo, H.; Osuka, A.
J. Am. Chem. Soc. 2008, 130, 14440. (d) Yamaguchi, S.; Shinokubo, H.;
Osuka, A. Inorg. Chem. 2009, 48, 795.
Figure 2. X-ray crystal structure of 4a: (a) top view and (b) side
view. The ellipsoids are scaled to the 50% probability. One of
two porphyrins and solvent molecules are omitted for clarity.
Substituents on the phenyl groups in the side view are omitted
for clarity.
Org. Lett., Vol. 14, No. 11, 2012
2779

In order to study how effectively the two neighboring
2-pyridyl substituents assist the nucleophilic addition of
phenylethynyllithium via coordination, we examined the
reactions of porphyrin 5 and β-monopyridyl-porphyrin 7
by changing the reaction conditions (Table 1). Porphyrin 5
did not afford phenylethynylated product 6 at 0 °C or
room temperature, but the reaction at 60 °C afforded 6 in
22% yield. An elongated reaction time merely resulted in
complicated mixtures. A certain improvement was ob-
served for 7, in that the reaction of 7 at room temperature
gave phenylethynylated product 8 in 23% yield. However,
the reaction at 70 °C gave a complicated mixture. These
results underscore the importance of two 2-pyridyl sub-
stituents for the smooth phenylethynylation reaction.
can be employed in this reaction, giving products 4bꢀe in
good yields (Scheme 1). Due to their attenuated nucleo-
philicity of the electron-deficient arylethynyllithium, a
longer reaction time improved the yields. 1-Hexynyl-
lithium gave 4f in good yield, and a conjugated alkynyl-
lithium, 3-methylbut-3-ene-1-ynyllithium, provided 4g.
Furthermore, the reactions of trimethylsilylethynyllithium
and ferrocenylethynyllithium gave4hand 4j in good yields.
When subjected to the comparable conditions, the corre-
sponding Zn(II) complex 1Zn and free base 1H were
recovered almost quantitatively. The structures of 4b
and 4h have been also determined by X-ray analysis
(Supporting Information (SI)),12,13 with both displaying
saddle-type distorted conformations, deviations of the
meso-alkynyl substituents, and outer-orienting pyridyl
groups similar to 4a.
Table 1. Synthesis of meso-Phenylethynyl Porphyrinsa
Figure 3. UVꢀvis absorption spectra of 1Ni (black), 4b (red), 4c
(blue), 4e (green), and 4f (pink) in CH2Cl2.
time
(h)
temp
yield
(%)
compd
(°C)
product
The meso-alkynylated porphyrins 4 show the perturbed
and red-shifted UVꢀvis absorption spectra as compared
with 1Ni (Figure 3). Electron-donating arylethynyl sub-
stituents tend to shift Soret-like bands to the lower energy
side. In particular, the absorption spectrum of 4c exhibits a
split and substantially red-shifted Soret band at 443 and
472 nm and a Q-band at 633 nm, probably reflecting the
strong electron-donating character of the (4-dimethyl-
aminophenyl)ethynyl substituent.
5
5
5
5
7
7
7
3
0
6
6
6
6
8
8
8
0
3
rt
60
60
0
<1
22
CM
0
3
12
3
12
12
rt
70
23
CM
a rt = room temperature. CM = complicated mixture.
Finally, the reaction of 1Ni with meso-ethynylatedNi(II)
porphyrin 9 was attempted. After extensive experimenta-
tion, the use of lithium hexamethyldisilazide (LiHMDS) as
a base was found to furnish meso-ethynylene-bridged di-
porphyrin 10 in 60% yield (Scheme 2). The HR-ESI-TOF
The meso-alkynylation reaction of 1Ni has proven to be
applicable to a wide rangeof alkynyllithium reagents. Both
electron-rich and -deficient arylethynyllithium reagents
(8) Song, J.; Aratani, N.; Heo, J. H.; Kim, D.; Shinokubo, H.; Osuka,
A. J. Am. Chem. Soc. 2010, 132, 11868.
(9) Yoshida, K.; Yamaguchi, S.; Osuka, A.; Shinokubo, H. Organo-
metallics 2010, 29, 3997.
(10) Anabuki, S.; Shinokubo, H.; Aratani, N.; Osuka, A. Angew.
Chem., Int. Ed. 2012, 51, 3174.
(12) Crystal data for 4b: C81H84N6NiO C6H6, Mw = 1294.36,
3
˚
triclinic, space group P1 (no. 2), a = 13.467(5) A, b = 16.348(5) A,
˚
˚
c = 18.590(5) A, α = 103.845(5)°, β = 105.316(5)°, γ = 106.968(5)°, V =
3
3547(2) A , Z = 2, T = 93(2) K, Dcalcd = 1.212 g cmꢀ3, R1 = 0.0430
˚
(I > 2σ(I)), Rw = 0.1168 (all data), GOF = 1.032; CCDC 872912.
(13) Crystal data for 4h: C77H86N6NiSi (water)3, Mw = 1294.36,
(11) Crystal data for 4a: C80H82N6Ni (C2H4Cl2)0.315 (CH3CN)3
-
(methanol)0.185, Mw = 1284.17, triclinic, space group P1 (no. 2), a =
3
3
3
3
˚
˚
˚
˚
orthorhombic, space group Cmca (no. 64), a = 28.3019(6) A, b =
14.6275(3) A, b = 20.5197(4) A, c = 24.8238(4) A, α = 98.9918(7)°, β =
3
3
˚
˚
˚
˚
104.1374(7)°, γ = 94.1415(7)°, V = 7088.9(2) A , Z = 4, T = 93(2) K,
11.8093(2) A, c = 42.6587(8) A, V = 14257.6(5) A , Z = 8, T = 93(2) K,
Dcalcd = 1.147 g cmꢀ3, R1 = 0.0877 (I > 2σ(I)), Rw = 0.2968 (all data),
GOF = 1.065; CCDC 872910.
Dcalcd = 1.203 g cmꢀ3, R1 = 0.0648 (I > 2σ(I)), Rw = 0.1911 (all data),
GOF = 1.077; CCDC 872911.
2780
Org. Lett., Vol. 14, No. 11, 2012

Scheme 2. Synthesis of Diporphyrin 10a
Figure 4. UVꢀvis absorption spectra of 10 (red) and 11 (black)
in CH2Cl2.
restricted perpendicular conformation due to the repulsion
between the appended porphyrin and two pyridyl groups.14
In summary, the direct meso-alkynylation of 1Ni pro-
ceeded smoothly with various alkynyllithium reagents.
This reaction is probably assisted by the double coordina-
tion of the pyridyl groups to the lithium reagent. The
ethynylene-bridged diporphyrin 10 was prepared by this
method. Coordination-assisted nucleophilic addition reac-
tions may have wider applicability with regard to a co-
ordinating group and nucleophile. Along this line, the
application of this strategy to other useful reactions is
now actively being studied in our laboratory.
a Ar = 3,5-di-tert-butylphenyl.
mass measurement detected the parent ion peak of 10 at
m/z = 2040.0765 (calcd for C136H149N10Ni2 = 2040.0727
[M þ H]þ). The 1H NMR spectrum of 10 is fully consistent
with its unsymmetrical structure, displaying one singlet
and six doublets due to the β-protons and four signals due
to the pyridyl protons (SI), among which Ha and Hb
protons are observed at 6.67 and 5.67 ppm owing to the
diatropic ring current of the attached porphyrin. Figure 4
shows the UVꢀvis absorption spectrum of 10 along with
that of meso-ethynylene-bridged diporphyrin 11 as a
reference. The absorption spectrum of 10 exhibits a broad
Soret band at 446 nm and Q-bands at 548, 600, and 714 nm,
which are significantly different from those of 11. This
result suggests that the diporphyrin 10 is forced to take a
Acknowledgment. This work was partly supported by
Grants-in-Aid for Scientific Research (No. 18685013; Nos.
19205006 (A) and 20108001 “pi-Space”) from MEXT and
by the JST PRESTO program. S.T. thanks the JSPS
Research Fellowship for Young Scientists program.
Supporting Information Available. Preparation and
analytical data for samples, and crystallographic data
(CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
(14) Tsuda, A.; Hu, H.; Tanaka, R.; Aida, T. Angew. Chem., Int. Ed.
2005, 44, 4884.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 11, 2012
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