Carbolithiation of meso-aryl-substituted 5,15-diazaporphyrin selectively provides 3-alkylated diazachlorins

Article abstract of DOI:10.1039/c3cc41907j

Treatment of meso-mesityl 5,15-diazaporphyrin with alkyllithiums in toluene at low temperature provided monoalkylated diazachlorins through highly regioselective nucleophilic addition at the β-position near the meso-nitrogen atom. The Royal Society of Che

Full text of DOI:10.1039/c3cc41907j

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Carbolithiation of meso-aryl-substituted
5,15-diazaporphyrin selectively provides
3-alkylated diazachlorins†
Cite this: Chem. Commun., 2013,
49, 5064
Received 14th March 2013,
Accepted 15th April 2013
Ayaka Yamaji, Satoru Hiroto, Ji-Young Shin and Hiroshi Shinokubo*
DOI: 10.1039/c3cc41907j
www.rsc.org/chemcomm
Treatment of meso-mesityl 5,15-diazaporphyrin with alkyllithiums
in toluene at low temperature provided monoalkylated diazachlorins
through highly regioselective nucleophilic addition at the b-position
near the meso-nitrogen atom.
Chlorin, 2,3-dihydroporphyrin, is the key structure of chloro-
phylls, which are important chromophores in Nature.1 Chlorins
display characteristic absorption features including a weakened
Soret band and bathochromically shifted and intensified
Q-bands in comparison to those of porphyrins. The characteristic
absorption phenomenon of chlorins fits with the light-harvesting
functions of photosynthetic antennae.
Scheme 1 Preparation of 5,15-diazaporphyrin 2 from dipyrrin Ni(II) complex 1.
of the outer nitrogen via coordination with lithium would
Recently, we have reported the synthesis of meso-aryl- enhance the efficacy of the addition process and result in high
substituted Ni(II) 5,15-diazaporphyrin 2 via Buchwald–Hartwig regioselectivity. In fact, we found that organolithium reagents
amination of the dichlorodipyrrin Ni(II) complex 1 (X = Cl) with added to 5,15-diazaporphyrin 2 with perfect regioselectivity to
benzylamine through C–N and C–C coupling.2 Matano and afford 3-alkylated 5,15-diazachlorins (Scheme 2).
co-workers have independently established a highly effective
We found that treatment of 10,20-dimesityl-5,15-diazaporphyrin
synthetic procedure for the preparation of diazaporphyrin 2 from 2 with methyllithium in THF at À78 1C provided b-alkylated
1 (X = Br) with metal azide as the nitrogen source (Scheme 1).3 diazaporphyrin 3a in 10% yield through regioselective addition
The metal template strategy with dipyrrin metal precursors 1 has of the methyl group to 2. The 1H NMR spectrum of 3a displays
proven to be quite powerful to create new types of porphyrinoids six doublet peaks and one singlet peak for b-pyrrolic protons.
including heterocorroles and heteroporphyrins.4
The NOESY spectrum of 3a exhibits distinct correlation between the
One of the key features of 5,15-diazaporphyrins is their singlet b-pyrrolic proton and the ortho-methyl protons of the mesityl
relatively low-lying LUMO due to electron-accepting sp2 nitro- group, which suggests that the alkylation occurred at the C3-position
gen atoms. We then became interested in the introduction of (ESI,† Fig. S3). The structure of 3a was unambiguously elucidated
substituents to diazaporphyrins by carbolithiation, because using X-ray diffraction analysis, which confirmed introduction of the
nucleophilic addition of alkyllithiums to pyridines is well methyl group at the proximal b-position (C3-position) to the outer
known to be an efficient method to prepare substituted nitrogen atom (Fig. 1a).
pyridines.5 It has also been reported that regular porphyrins
are susceptible to nucleophilic attack by alkyllithiums6 both at
meso- and b-positions.7 We anticipated that the directing effect
Department of Applied Chemistry, Graduate School of Engineering,
Nagoya University, Chikusa-ku, Nagoya 464-8603, Japan.
E-mail: hshino@apchem.nagoya-u.ac.jp; Fax: +81-52-789-3188
† Electronic supplementary information (ESI) available: Experimental proce-
dures, spectral data of all new compounds, photophysical data, and crystal-
lographic data of 3a, 4a and 3e. CCDC 928786–928788. For ESI and
crystallographic data in CIF or other electronic format see DOI: 10.1039/
Scheme 2 Nucleophilic addition of alkyllithiums to 2.
c3cc41907j
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Table 1 Nucleophilic addition of alkyllithiums to 2a
Diazaporphyrin yield (%)
Diazachlorin yield (%)
R
Solvent
THF
Me
Me
3a
10
6
4a
4a
4b
4c
4d
4e
Trace
42
12
17
48
Toluene 3a
n-Bu Toluene 3b
s-Bu Toluene 3c
t-Bu Toluene 3d
27
12
Trace
18
Ph
Toluene 3e
Trace
a
Reaction conditions: diazaporphyrin (0.025 mmol), alkyllithium
(0.2 mmol), solvent (5 mL), À78 1C, 3.5 h.
b-alkylated diazaporphyrins and diazachlorins with perfect
regioselectivity (Table 1). The use of phenyllithium furnished
phenyldiazaporphyrin 3e exclusively probably due to effective
conjugation between the phenyl group and the diazaporphyrin
core, suggested by the rather small dihedral angle (22.51) between
the phenyl group and the adjacent pyrrole unit (Fig. 1e and f).3 In
the crystal packing, two molecules of 3e assemble through p–p
stacking between the phenyl ring and the diazaporphyrin core, the
interplanar distance of which is 3.53 Å.
The observed regioselectivity can be accounted for by a directing
effect of the outer nitrogen atom, which facilitates the nucleophilic
attack of the alkyllithium reagent at the C3-position through coordi-
nation with lithium (Scheme 3). The DFT calculations estimated that
the resulting anionic intermediate A is more stable by 7.5 kcal molÀ1
than B, which could result from alkylation at the C2-position.
Formation of the anionic species after carbolithiation was confirmed
by the trapping experiment of the intermediate with deuterium
oxide, providing 2-deuterated 4a with 43% of isotope labelling.
The UV/vis absorption spectrum of b-alkylated diazachlorin
4a was almost identical with that of diazachlorin 5 which was
obtained through hydrogenation of 2 with p-tosylhydrazide
under basic conditions (Fig. 2).9 Compared to diazaporphyrin
3a, diazachlorins 4a and 5 exhibited weakened Soret bands
along with substantially red shifted Q-bands (ca. 60 nm). The
characteristic changes are consistent with the general trend
typically observed from porphyrin to chlorin. These changes are
due to symmetry lowering to weaken degeneracy of the frontier
orbitals, resulting in smaller configuration interaction. In fact,
Fig. 1 Crystal structures of 3a (a) top view and (b) side view, 4a (c) top view and
(d) side view and 3e (e) top view, (f) side view and (g) dimeric structure in the
crystal packing. meso-Aryl substituents are omitted for clarity. The thermal
ellipsoids are scaled to the 50% probability level.
We then checked the solvent effect on alkylation. To our
delight, we found that the use of toluene as the reaction solvent
dramatically changed the reaction profile to afford b-alkylated
diazachlorin 4a in 42% yield along with diazaporphyrin 3a in
6% yield without changing the regioselectivity in the addition
process.8 The 1H NMR spectrum of 4a exhibited six doublet
peaks for b-protons in the aromatic region from d = 8.0 to 8.8 as
well as for protons on sp3 carbons, which were observed in the
up-field region from d = 3.4 to 4.6. This clearly suggests the
presence of the saturated carbon centre. The structure of 4a was
confirmed using X-ray diffraction analysis. As shown in Fig 1b,
the structure of diazachlorin 4a is rather planar. The C2–C3
bond length is 1.54 Å, confirming its single bond nature. While
diazachlorin 4a was stable enough under ambient conditions,
treatment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
in dichloromethane readily oxidized 4a to diazaporphyrin 3a
quantitatively.
Other organolithium reagents such as n-BuLi, s-BuLi, t-BuLi and
PhLi also induced carbolithiation to provide the corresponding
Scheme 3 Proposed reaction pathway and calculated energy difference
between the intermediates at the B3LYP/631SDD level.
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large Q-band, suggesting potential application of diazachlorins
to light-harvesting materials.
The work was supported by Grants-in-Aid for Scientific Research
(No. 24350023) and Program for Leading Graduate Schools
‘‘Integrative Graduate Education and Research in Green Natural
Sciences’’, MEXT, Japan. H.S. acknowledges Yazaki Memorial
Foundation for Science and Technology for financial support.
Notes and references
1 (a) H. Tamiaki and M. Kunieda, in Handbook of Porphyrin Science,
ed. K. M. Kadish, K. M. Smith and R. Guilard, World Scientific,
Singapore, 2011, vol. 11, pp. 223–290; (b) Handbook of Porphyrin
Science, ed. K. M. Kadish, K. M. Smith and R. Guilard, World
Scientific, Singapore, 2012, vol. 20.
2 M. Horie, Y. Hayashi, S. Yamaguchi and H. Shinokubo, Chem.–Eur. J.,
2012, 18, 5919.
3 Y. Matano, T. Shibano, H. Nakano and H. Imahori, Chem.–Eur. J.,
2012, 18, 6208.
Fig. 2 UV/vis absorption spectra of 3a, 4a and 5 measured in dichloromethane.
4 (a) T. Ito, Y. Hayashi, S. Shimizu, J.-Y. Shin, N. Kobayashi and
H. Shinokubo, Angew. Chem., Int. Ed., 2012, 51, 8542; (b) H. Kamiya,
T. Kondo, T. Sakida, S. Yamaguchi and H. Shinokubo, Chem.–Eur. J.,
the DFT calculation revealed the larger energy gap between
HOMO and HOMO–1 of 4a than that of 3a (Fig. S21, ESI†).
Electrochemical properties of 3a and 4a were examined
using cyclic voltammetry (ESI,† Fig. S20). One reversible oxida-
tion wave and two reversible reduction waves were observed
for diazaporphyrin 3a, while diazachlorin 4a exhibited one
reversible reduction and one reversible oxidation wave. The
electrochemical HOMO–LUMO gaps for 3a and 4a were deter-
mined to be 2.18 and 1.93 V, respectively. The narrower
HOMO–LUMO gap of 4a matches well with the optical analysis
and theoretical calculations. The saturation of the Cb–Cb bond
did not alter the reduction potential (À1.44 V for 3a vs. À1.49 V
for 4a) but induced a substantial cathodic shift in the oxidation
potential (0.74 V for 3a vs. 0.44 V for 4a).
¨
2012, 18, 16129; (c) D. Sakow, B. Boker, K. Brandhorst, O. Burghaus
¨
and M. Broring, Angew. Chem., Int. Ed., 2013, 52, 4912.
5 (a) J. C. W. Evans and C. F. H. Allen, Org. Synth., 1943, Coll. vol. II, 517;
(b) C. S. Giam and J. L. Stout, J. Chem. Soc., Chem. Commun., 1970, 478.
6 (a) J. Clayden, Organolithiums: Selectivity for Synthesis, Pergamon,
Oxford, 2002; (b) The Chemistry of Organolithium Compounds, ed.
Z. Rappoport and I. Marek, John Wiley & Sons, New York, 2004.
7 (a) M. O. Senge, W. W. Kalisch and I. Bischoff, Chem.–Eur. J., 2000,
6, 2721; (b) W. W. Kalisch and M. O. Senge, Angew. Chem., Int. Ed., 1998,
37, 1107; (c) I. Bischoff, X. Feng and M. O. Senge, Tetrahedron, 2001,
57, 5573; (d) M. O. Senge, J. Richter, I. Bischoff and A. Ryan, Tetrahedron,
2010, 66, 3508; (e) B. Krattinger and H. J. Callot, Tetrahedron Lett., 1996,
37, 7699; ( f ) B. Krattinger and H. J. Callot, Tetrahedron Lett., 1998,
39, 1165; (g) B. Krattinger and H. J. Callot, Eur. J. Org. Chem., 1999, 1857.
8 The starting material 1 was also recovered in ca. 30%. In addition,
trace amounts of dialkylated diazaporphyrins and diazabacterio-
chlorins were detected. Probably dialkylation is unfavorable because
of unstable dilithiated species even in the presence of an excess
amount of the alkyllithium. The present alkylation was also applic-
able for 3,5-di-tert-butyldiphenyl-substituted diazaporphyrin.
9 H. W. Whitlock, R. Hanauer, M. Y. Oester and B. K. Bower, J. Am.
Chem. Soc., 1969, 91, 7485.
In conclusion, 5,15-diazachlorins were readily prepared
by regioselective nucleophilic addition of alkyllithiums to
5,15-diazaporphyrin. Similarly to the absorption features of
typical chlorins, diazachlorins exhibited a red-shifted and relatively
c
5066 Chem. Commun., 2013, 49, 5064--5066
This journal is The Royal Society of Chemistry 2013