Silylethynyl substituents as porphyrin protecting groups for solubilization and selectivity control

Article abstract of DOI:10.1021/ol500569b

Silylethynyl substituents are proposed as protecting groups for porphyrin derivatives to enhance their solubility and enable regioselective functionalization. After usage as protecting groups, silylethynyl groups at the meso-positions can be efficiently removed upon heating with aqueous H ₂SO₄ in the presence of a surfactant. This approach was applied to the preparation of unsymmetrically β-substituted porphyrins and porphin-porphyrin oligomers, which were inaccessible by conventional methods.

Full text of DOI:10.1021/ol500569b

Letter
pubs.acs.org/OrgLett
Silylethynyl Substituents as Porphyrin Protecting Groups for
Solubilization and Selectivity Control
Kazuma Oda, Masanari Akita, Satoru Hiroto,* and Hiroshi Shinokubo*
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Nagoya, 464-8603, Japan
S
* Supporting Information
ABSTRACT: Silylethynyl substituents are proposed as protecting groups for
porphyrin derivatives to enhance their solubility and enable regioselective
functionalization. After usage as protecting groups, silylethynyl groups at the
meso-positions can be efficiently removed upon heating with aqueous H2SO4
in the presence of a surfactant. This approach was applied to the preparation
of unsymmetrically β-substituted porphyrins and porphin−porphyrin
oligomers, which were inaccessible by conventional methods.
Table 1. Dealkynylation of meso-Dialkynylporphyrins
orphyrins have attracted much attention as catalysts for
organic reactions, building blocks for supramolecules, and
P
materials for optoelectronic devices.1 As a result, a number of
synthetic procedures for various porphyrins have been
developed.2 However, no convenient methods to protect the
reactive meso-carbon atoms in porphyrins have been estab-
lished, although some removable meso-substituents are known.
Neya et al. reported that treatment of tetra-tert-butylporphyrin
with H2SO4 produced porphin, a porphyrin without any
substituents, in moderate yield.3 This method, however, is
useful only for the synthesis of porphin. Other defunctionaliza-
tions at the meso-positions involve decarboxylation processes.4
Unfortunately, such carbonyl substituents are not useful as
protecting groups owing to their high reactivity. Recently,
Osuka and co-workers reported palladium-catalyzed reductive
debromination at the meso-positions. However, halogen
substituents often reduce the solubility of these substrates in
organic solvents and they also do not survive during transition-
metal-catalyzed reactions.5
Silylethynyl groups not only enhance the solubility of π-
conjugated molecules due to the bulky silyl groups,6 but the
electron-withdrawing nature of the alkyne moiety also improves
the stability of unstable compounds such as higher acenes7 and
radicals.8 The installation of trialkylsilylethynyl groups on
various π-systems can be readily achieved via Sonogashira
coupling. However, no removal methods have been available.
Herein we report our serendipitous finding of the deal-
kynylation reaction of meso-ethynylporphyrins. We also
demonstrate the utility of silylethynyl protection for regiose-
lective functionalization of porphyrins through temporary
masking of the reactive meso-positions.
yield
entry
M
additive time (h)
solvent
2
3
4
1
2
3
4
Zn
Ni
Ni
Ni
Ni
none
none
none
SDS
16
10
12
24
12
ClCH2CH2Cl
ClCH2CH2Cl
C6H4Cl2
54
−
99
6
8
<1
−
0
45
−
63
ClCH2CH2Cl
ClCH2CH2Cl
0
a
5
none
<1
<1
75
a
DBSA was employed instead of H2SO4.
(entry 2). Interestingly, the reaction was heavily dependent on
the solvent: diacetyl product 2H was quantitatively obtained in
1,2-dichlorobenzene (entry 3). The reaction conditions were
further optimized, and the addition of sodium dodecyl sulfate
(SDS) enhanced the yield of 4Ni to 63% (entry 4).10 Other
surfactants, such as Triton-X100 and cetyltrimethylammonium
bromide, did not work well. The use of dodecylbenzenesulfonic
acid (DBSA) instead of the sulfuric acid−SDS combination
provided 4Ni in 75% yield (entry 5).11 These results suggest
that the effective mixing of the organic and aqueous phases is
the key to successful dealkynylation.
To prepare diacetylporphyrin, we performed the hydration of
bis(trimethylsilylethynyl)porphyrin Zn(II) 1Zn with aqueous
sulfonic acid (25% aq.) in 1,2-dichloroethane (Table 1).9 The
reaction successfully afforded the desired product 2H in 54%
yield. To our surprise, however, acetyl product 3H and meso-
unsubstituted porphyrin 4H were also obtained as byproducts
in 8% and 6% yields, respectively (entry 1). Ni(II) complex 1Ni
also underwent dealkynylation to afford 4Ni in 45% yield
Received: February 21, 2014
Published: March 3, 2014
© 2014 American Chemical Society
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Letter
The scope of this dealkynylation procedure was investigated
(Scheme 1). Di(phenylethynyl)porphyrin Ni(II) 5Ni also
on the carbonyl group induces cleavage of the C−C bond to
provide the corresponding meso-unsubstituted porphyrin and
the carboxylic acid. The generation of a carboxylic acid was
confirmed in the reaction of anthrylethynylporphyrin Ni(II)
7Ni, which provided 4Ni along with anthrylacetic acid (Scheme
3). The formation of anthrylacetic acid was assigned by the
Scheme 1. Dealkynylation and Deacetylation of 5,15-
Diarylporphyrins
1
fluorescence and H NMR spectra compared to the authentic
sample.
Scheme 3. Detection of a Carboxylic Acid
afforded the dealkylated product 4Ni but in low yield (12%),
while diethynylporphyrin 6Ni provided 4Ni in 68% yield. This
result indicates the dealkynylation does not require silyl groups
if the substrate is sufficiently soluble. Notably, the reaction of
diacetylporphyrin 2Ni under the optimized conditions
furnished 4Ni in 92% yield, indicating that dealkynylation
proceeds through the diacetylporphyrin intermediate.
The utility of the present dealkynylation protocol was
demonstrated by synthesizing porphin−porphyrin oligomers
10 (Scheme 4). Porphin is a useful motif for construction of π-
stacking structures. However, introduction of a porphin unit is
challenging because of the insoluble nature of porphin.
Precursory porphyrin dimer 9a and trimer 9b were prepared
through Suzuki−Miyaura coupling of 5-bromo-10,20-bis(silyl-
ethynyl)porphyrin 8a and 5,15-dibromo-10,20-bis(silyl-
ethynyl)porphyrin 8b.13 Desilylation of 9a using tetrabutyl-
ammonium fluoride (TBAF), followed by dealkynylation with
DBSA, produced 10a in 58% yield. meso-Unsubstituted meso−
meso linked porphyrin trimer 10b was also synthesized from 9b
in 56% yield. Consequently, the bis(triisopropylsilylethynyl)-
porphyrin group can serve as a synthetic equivalent to porphin,
for which the insolubility can be circumvented by the bulky silyl
group.
On the basis of these observations, we propose a plausible
reaction mechanism in Scheme 2. The reaction goes through
Scheme 2. Plausible Dealkynylation Mechanism
The structure of porphin−porphyrin 10a was unambiguously
elucidated by X-ray diffraction analysis (Figure 1).14 As
expected, two porphin rings are mutually stacked in a face-to-
face manner. The interplanar distance is 3.67 Å, which is within
the sum of the van der Waals radii of two carbon atoms.
We further investigated the use of alkynyl protection for the
synthesis of unsymmetrically substituted porphyrins. Recently,
transition-metal-catalyzed C−H borylation and arylation have
been developed for late-stage functionalization of porphyrins at
β-positions with high regioselectivity.15,16 These procedures,
however, could not control the regioselectivity of two
introduced substituents, resulting in a mixture of three isomers.
We expected combining the iridium-catalyzed direct borylation
reaction with the present alkyne protection method enabled the
controlled synthesis of unsymmetrically β-substituted porphyr-
ins 14 from silylethynylporphyrin Ni(II) 11 (Scheme 5).
Iridium-catalyzed direct borylation of 11 with bis(pinacolate)-
diboron (pin2B2) and 4,4-di-tert-butyl-2,2-bipyridyl (dtbpy) in
the sequence of hydrolysis and retro-Friedel−Crafts acylation.12
Initially, regioselective protonation and hydration of the alkyne
moiety affords the α-silyl ketone, which is readily transformed
to acetylporphyrin A via protodesilylation. In the next step,
protonation at the meso-position occurs with the aid of electron
donation from the nitrogen atom. Finally, the attack of water
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Letter
Scheme 4. Synthesis of Porphin−Porphyrin Oligomers 10
Scheme 5. Synthesis of Unsymmetrically β-Substituted
Porphyrins
nitrophenyl groups at the β-positions in 74% yield (two steps).
Desilylation of 13 with TBAF followed by dealkynylation with
DBSA in 1,2-dichloroethane provided 14 in 53% yield.
In conclusion, we have developed a method for deal-
kynylation of meso-alkynylporphyrins through acid-mediated
hydrolysis that is enhanced by the addition of an anionic
surfactant. Using this protocol, porphin−porphyrin oligomers
were prepared. Furthermore, the utility of alkynyl substituents
as protecting groups in the synthesis of unsymmetrically β-
substituted porphyrins was demonstrated. We believe that the
present dealkynylation procedure enables the facile synthesis of
intriguing porphyrins that have previously been inaccessible by
conventional methods.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details and spectral data for all new compounds.
Crystallographic data (CIF file) for 10a. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: hshino@apchem.nagoya-u.ac.jp.
*E-mail: hiroto@apchem.nagoya-u.ac.jp.
Figure 1. X-ray crystal structure of porphin−porphyrin dimer 10a. (a)
Side view, (b) front view, and (c) packing structure in crystal. The
thermal ellipsoids are scaled at the 50% probability level. tert-Butyl
substituents are omitted for clarity.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by Grants-in-Aid for Scientific
Research (Nos. 25410039 and 24350023) and the Program for
Leading Graduate Schools “Integrative Graduate Education and
Research in Green Natural Sciences”, MEXT, Japan. H.S.
mesitylene produced the corresponding borylated porphyrin 12
quantitatively. The subsequent Suzuki−Miyaura cross-coupling
with 4-bromonitrobenzene afforded porphyrin 13 with two
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Letter
acknowledges Toyoaki Schlorship Foundation for financial
support.
REFERENCES
■
(1) (a) Kadish, K., Smith, K. M., Guilard, R., Eds. The Porphyrin
Handbook Vol. 11−20; Academic Press: Boston, 2003. (b) Kadish, K.,
Smith, K. M., Guilard, R., Eds. Handbook of Porphyrin Science Vol. 1−
30; World Scientific Publishing Co. Pte. Ltd.: Singapore, 2010.
(2) Aratani, N.; Osuka, A. In Handbook of Porphyrin Science, Vol. 1;
Kadish, K., Smith, K. M., Guilard, R., Eds.; World Scientific Publishing
Co. Pte. Ltd.: Singapore, 2010; p 1.
(3) (a) Neya, S.; Funasaki, N. Tetrahedron Lett. 2002, 43, 1057.
(b) Ryppa, C.; Senge, M. O.; Hatscher, S. S.; Kleinpeter, E.; Wacker,
P.; Schilde, U.; Wiehe, A. Chem.Eur. J. 2005, 11, 3427.
(4) Neya, S.; Quan, J.; Hata, M.; Hoshino, T.; Funasaki, N.
Tetrahedron Lett. 2006, 47, 8731.
(5) Sahoo, A. K.; Nakamura, Y.; Aratani, N.; Kim, K. S.; Noh, S. B.;
Shinokubo, H.; Kim, D.; Osuka, A. Org. Lett. 2006, 8, 4141.
(6) Anthony, J. E.; Eaton, D. L.; Parkin, S. R. Org. Lett. 2002, 4, 15.
(7) (a) Payne, M. M.; Parkin, S. R.; Anthony, J. E. J. Am. Chem. Soc.
2005, 127, 8028. (b) Purushothaman, B.; Bruzek, M.; Parkin, S. R.;
Miller, A.-F.; Anthony, J. E. Angew. Chem., Int. Ed. 2011, 50, 7013.
(8) Munto, H. E.; Marvel, C. S. J. Am. Chem. Soc. 1932, 54, 4445.
(9) Tokuji, S.; Maeda, C.; Yorimitsu, H.; Osuka, A. Chem.Eur. J.
2011, 17, 7154.
(10) The use of Ultrapur-100 grade H2SO4 which contained a very
low amount of metal impurities at the ppb level resulted in no change
in the reaction profile. The effect of possible metal impurities was also
checked by the additive test. The addition of Fe2+, Fe3+, and Pb2+ in
the reaction media did not produce the dealkynylated products.
(11) DBSA was used as a dehydration reagent in aqueous media. For
example: Manabe, K.; Iimura, S.; Sun, X.-M.; Kobayashi, S. J. Am.
Chem. Soc. 2002, 124, 11971.
(12) For deacetylation with a super acid, see: (a) Olah, G. A.; Laali,
K.; Mehrotra, A. K. J. Org. Chem. 1983, 48, 3360. (b) Kozelj, M.;
Petric, A. Synlett 2007, 11, 1699.
(13) Screen, T. E. O.; Lawton, K. B.; Wilson, G. S.; Dolney, N.;
Ispasoiu, R.; Goodson, T., III; Martin, S. J.; Bradley, D. D. C.;
Andrson, H. L. J. Mater. Chem. 2001, 11, 312.
(14) Crystallographic data for 10a: C76H68N8OCl2Ni2, Mw =
1278.14, triclinic, P1, a = 11.636(2) Å, b = 15.963(3) Å, c = 19.746
̅
(4) Å, α = 102.414(2)°, β = 101.791(2)°, γ = 108.945(2)°, Z = 2, R =
0.0547 (I > 2.0 σ(I)), Rw = 0.1756 (all data), GOF = 1.130.
(15) (a) Hata, H.; Shinokubo, H.; Osuka, A. J. Am. Chem. Soc. 2005,
127, 8264. (b) Hata, H.; Yamaguchi, S.; Mori, G.; Nakazono, S.;
Katoh, T.; Takatsu, K.; Hiroto, S.; Shinokubo, H.; Osuka, A. Chem.
Asian J. 2007, 2, 849.
(16) (a) Kawamata, Y.; Tokuji, S.; Yorimitsu, H.; Osuka, A. Angew.
Chem., Int. Ed. 2011, 50, 8867. (b) Yamamoto, Y.; Tokuji, S.; Tanaka,
T.; Yorimitsu, H.; Osuka, A. Asian J. Org. Chem. 2013, 2, 320.
1821
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