Novel porphyrin-quinone architectures via 1,3-dipolar cycloaddition reactions

Article abstract of DOI:10.1016/j.tetlet.2005.06.074

Porphyrinic pyridinium ylides react with 1,4-benzoquinone and 1,4-naphthoquinone to afford novel meso-substituted indolizine porphyrins.

Full text of DOI:10.1016/j.tetlet.2005.06.074

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5487–5490
Novel porphyrin-quinone architectures via 1,3-dipolar
cycloaddition reactions
´
Shengxian Zhao, Maria G. P. M. S. Neves, Augusto C. Tome,
*
´
Artur M. S. Silva and Jose A. S. Cavaleiro
Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Received 15 March 2005; revised 8 June 2005; accepted 14 June 2005
Available online 5 July 2005
Abstract—Porphyrinicpyridinium ylides react with 1,4-benzoquinone and 1,4-naphthoquinone to afford novel meso-substituted
indolizine porphyrins.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Nature has built up complicated photosystems over
billions of years for photochemical conversion and stor-
age of energy. During the last decades, a great number
of biomimeticmodel systems have been used to study
the photosynthetic electron-transfer mechanism.1 There-
fore, numerous covalently linked porphyrin-quinone
compounds, with different bridging features, have been
designed and studied for that purpose.2
ence of a base (K2CO3 or DBU).10 As indicated in
Scheme 1, the 1,3-dipolar cycloaddition product formed
in this reaction depends on the base used. When potas-
sium carbonate was used, only the mono-addition com-
pound 2 (16% yield) was obtained; however, with DBU,
bis-addition occurred and the novel porphyrinic dimer 3
(23% yield) was the only isolated addition product. In
both cases, porphyrin 4 was also formed.
Over the past years, we3,4 and others5 have been investi-
gating the reactivity of porphyrins as dienophiles and
dipolarophiles in Diels–Alder and 1,3-dipolar cycloaddi-
tion reactions.6 As part of such studies, we have used
new porphyrin pyridinium salts as precursors of the cor-
responding ylides and investigated their reactivities with
quinones. It is known from the literature that in 1,3-
dipolar cycloadditions involving pyridinium salts, the
dipolarophiles are usually dialkyl acetylenedicarboxyl-
ates or a-bromo-a,b-unsaturated esters or nitriles;7
when electron-deficient alkenes are used as dipolaro-
philes the indolizine products are only isolated if the
reactions are carried out in the presence of an oxidant
(e.g., tetrakispyridinecobalt(II) dichromate or MnO2).8
In our present studies, the quinones were used in excess,
acting as reagents and as oxidants.
The structures of compounds 2 and 3 were deduced
1
from their H and 13C NMR spectra, UV–vis and mass
spectra.11,12 The 1H NMR spectrum of 2 shows a singlet
at d 4.18 ppm, corresponding to the methyl ester group,
and an AB spin system at d 6.81 and 6.83 ppm
(J = 10.3 Hz), corresponding to the two proton reso-
nances of the quinone moiety. The three protons at
the indolizine ring appear as three double doublets at
d 8.05 (J = 1.9 and 7.3 Hz), 9.29 (J = 0.9 and 1.9 Hz)
and 9.71 ppm (J = 0.9 and 7.3 Hz), while the protons
of the meso-phenyl groups appear as two multiplets at
d 7.74–7.80 and d 8.21–8.24 ppm. The eight b-pyrrolic
protons appear as two AB spin systems at d 8.86 (4H,
J = 4.8 Hz) and 8.90 ppm (4H, J = 4.8 Hz). The 13C
NMR spectrum of compound 2 shows the signals corre-
sponding to the three carbonyl groups at d 161.8 ppm
(ester group) and at d 181.3 and 182.1 ppm (quinone).
The FAB mass spectrum shows peaks at m/z 794 and
793, which are two units higher than the expected.
Presumably, this might be due to the reduction of the
quinone moiety, under the FAB conditions, and the
observed peaks correspond to [M+3H]+ (794) and to
[M+2H]+Å (793).13
We started these studies with the reaction of porphyrin-
pyridinium salt 19 with 1,4-benzoquinone in the pres-
Keywords: Porphyrins; Ylides; Cycloadditions; Quinones; Indolizine.
*
Corresponding author. Tel.: +351 234 370 717; fax: +351 234 370
084; e-mail: jcavaleiro@dq.ua.pt
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.074

5488
S. Zhao et al. / Tetrahedron Letters 46 (2005) 5487–5490
Ph
Ph
O
O
O
N
N
NH
N
NH
N
K2CO3
NCH2CO2CH3 Br
N
+
Ph
Ph
CO2CH3
toluene,
reflux
HN
HN
O
Ph
Ph
2
1
Ph
Ph
Ph
Ph
N
N
HN
NH
Ph
NH
HN
DBU
N
N
Ph
Ph
toluene,
reflux
N
NH
O
N
Ph
HN
N
N
N
H3CO2C
CO2CH3
Ph
O
4
3
Scheme 1.
1
When we compare the H NMR spectrum of 3 with the
one of compound 2, the main difference is the absence of
the signals corresponding to the protons of the quinone
moiety. This is clear evidence that a bis-addition
occurred. The mass spectrum of this compound shows
intense peaks at m/z 1475 ([M+H]+) and 1474 ([M]+Å),
confirming that it is in fact a bis-addition product. The
addition of a second porphyrinic pyridinium ylide to
compound 2, followed by aromatisation, could lead to
compound 3 or to its isomer 5. However, only one of
them was formed. The 13C NMR spectrum of the com-
pound shows three signals corresponding to carbonyl
groups: one at d 162.2 ppm corresponding to the ester
group, and the other two at d 177.5 and 177.9 ppm cor-
responding to the carbonyl groups of the quinone moi-
ety. This spectrum only fits with structure 3, since in
structure 5 there are only two non-equivalent carbonyl
groups. The formation of a mono-addition product
when potassium carbonate is used while a bis-addition
compound is formed in the presence of DBU is probably
related to the fact that in the first case there is a two-
phase reaction system, while with DBU it is a homoge-
nous reaction.
Porphyrin 4, a by-product of these reactions, results
from the dealkylation of 1. To confirm it, a toluene
solution of compound 1 in the presence of DBU or
K2CO3 (in the absence of any dipolarophile) was
refluxed for 8 h and in fact it was converted into 4
(60% yield). It has been shown in the literature that
the carbon–nitrogen bond cleavage in pyridinium com-
pounds corresponds to the oxidation of the carbanion
by oxygen.14
The cycloaddition reaction of pyridinium salt 1 with 1,4-
naphthoquinone and with dimethyl acetylenedicarboxyl-
ate afforded, respectively, compounds 6 (16% yield)15
and 7 (39% yield).16
Ph
N
NH
N
H3CO2C
Ph
N
HN
Ph
O
O
Ph
N
NH
N
N
Ph
CO2CH3
HN
5
Ph
Ph
Ph
O
H3CO2C
N
CO2CH3
CO2CH3
O
N
NH
N
NH
N
Ph
Ph
CO2CH3
HN
N
HN
N
6
7
Ph
Ph

S. Zhao et al. / Tetrahedron Letters 46 (2005) 5487–5490
5489
Ph
CH2CO2CH3 Br-
O
N
NH
N
N
Ph
+
HN
O
Ph
8
DBU, toluene, reflux
O
N
Ph
Ph
Ph
H3CO2C
N
O
CO2CH3
O
N
N
NH
N
NH
N
N
NH
N
N
Ph
+
Ph
Ph
+
HN
HN
HN
O
Ph
Ph
Ph
9
10
11
Scheme 2.
´
4. (a) Silva, A. M. G.; Tome, A. C.; Neves, M. G. P. M. S.;
Silva, A. M. S.; Cavaleiro, J. A. S. Chem. Commun. 1999,
The reaction of the pyridinium salt 8 with 1,4-naphtho-
quinone afforded the non-alkylated pyridyl porphyrin 9
(28% yield) and the two regioisomericocmpounds 10
(10% yield)17 and 11 (5% yield) (Scheme 2).18 We are
extending our studies to other dipolarophiles and to
di- and tetrapyridyl substituted porphyrins. Collabora-
tive theoretical studies related with the formation of
type 3 compounds have also been initiated.
´
1767–1768; (b) Silva, A. M. G.; Tome, A. C.; Neves, M.
G. P. M. S.; Silva, A. M. S.; Cavaleiro, J. A. S. J. Org.
Chem. 2002, 67, 726–732.
5. Flemming, J.; Dolphin, D. Tetrahedron Lett. 2002, 43,
7281–7283.
6. For a review on the cycloaddition reactions of porphyrins,
´
see: Cavaleiro, J. A. S.; Neves, M. G. P. M. S.; Tome, A.
C. Arkivoc 2003, xiv, 107–130 (www.arkat-usa.org).
7. Katritzky, A. R.; Qiu, G.; Yang, B.; He, H.-Y. J. Org.
Chem. 1999, 64, 7618–7621.
Acknowledgements
8. (a) Wei, X.; Hu, Y.; Li, T.; Hu, H. J. Chem. Soc., Perkin
Trans. 1 1993, 2487–2489; (b) Wang, B.; Zhang, X.; Li, J.;
Jiang, X.; Hu, Y.; Hu, H. J. Chem. Soc., Perkin Trans. 1
1999, 1571–1575; (c) Zhang, L.; Liang, F.; Sun, L.; Hu, Y.;
Hu, H. Synthesis 2000, 1733–1737.
9. Pyridinium salts 1 and 7 were obtained from the reaction
of the corresponding porphyrins 4 and 8 with methyl
bromoacetate in refluxing chloroform, a modification of
the procedure described in Zhang, L.; Liang, F.; Sun, L.;
Hu, Y.; Hu, H. Synthesis 2000, 1733–1737.
Thanks are due to the University of Aveiro, Fundac¸a˜o
ˆ
the Organic Chemistry Research Unit and Project POC-
TI/1999/QUI/32851. One of us (S. Zhao) is also grateful
to FCT for a Ph.D. grant (SFRH/BD/2936/2000).
para a Ciencia e a Tecnologia and FEDER for funding
References and notes
10. Typical procedure: To a toluene (6 mL) solution of 1
(20 mg) and 1,4-benzoquinone (56 mg, 20 equiv) was
added K2CO3 (180 mg, 50 equiv) [or DBU (0.19 mL,
50 equiv)]. The mixture was refluxed for 8 h. The reaction
mixture was cooled to room temperature and the toluene
was partially evaporated. The compounds were separated
by column chromatography using chloroform as eluent
and further purified by preparative TLC.
1. (a) Gust, D.; Moore, T. In The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic
Press: San Diego, 2000; Vol. 8, pp 153–190; (b) Piotro-
wiak, P. Chem. Soc. Rev. 1999, 28, 143–150; (c) Kurreck,
H.; Huber, M. Angew. Chem., Int. Ed. Engl. 1995, 34,
849–866; (d) Wasielewski, M. R. Chem. Rev. 1992, 92,
435–461.
2. (a) Springer, J.; Kodis, G.; Garza, L.; Moore, A. L.;
Moore, T. A.; Gust, D. J. Phys. Chem. A 2003, 107, 3567–
3575; (b) Kang, Y. K.; Rubtsov, I. V.; Ivine, P. M.; Chen,
J.; Therien, M. J. J. Am. Chem. Soc. 2002, 124, 8275–8279;
(c) Shi, X.; Amin, R.; Liebeskind, L. S. J. Org. Chem.
2000, 65, 1650–1654; (d) Shi, X.; Liebeskind, L. S. J. Org.
Chem. 2000, 65, 1665–1671; (e) Speck, M.; Kurreck, H.;
Senge, M. O. Eur. J. Org. Chem. 2000, 2303–2314; (f)
Wiehe, A.; Senge, M. O.; Scha¨fer, A.; Speck, M.; Tannert,
S.; Kurreck, H.; Ro¨der, B. Tetrahedron 2001, 57, 10089–
10110.
11. Selected data for compound 2: mp >300 ꢁC. 1H NMR
(300 MHz, CDCl3) d: À2.75 (s, 2H, NH), 4.18 (s, 3H,
CO2CH3), 6.81 and 6.83 (AB, 2H, quinone CH,
J = 10.3 Hz), 7.74–7.80 (m, 9H, Ph-Hmeta,para), 8.05 (dd,
1H, Indolizine-H, J = 1.9 and 7.3 Hz), 8.21–8.24 (m, 6H,
Ph-Hortho), 8.86 (AB, 4H, b-H, J = 4.8 Hz), 8.90 (AB, 4H, b-
H, J = 4.8 Hz), 9.29 (dd, 1H, Indolizine-H, J = 0.9 and
1.9 Hz), 9.71 (dd, 1H, Indolizine-H, J = 0.9 and 7.3 Hz). 13
C
NMR (75 MHz, CDCl3) d: 52.6 (CO2CH3), 111.7, 114.2,
115.3, 120.8, 121.2, 124.0, 125.1, 125.3, 126.8, 126.9, 127.9,
131.4, 131.8, 134.5, 134.6, 135.0, 139.2, 141.89, 141.91,
143.1, 146.4, 161.8 (CO2CH3), 181.3 and 182.1 (quinone
CO). UV–vis (CHCl3) kmax (loge): 420 (5.43), 516 (4.23),
556 (3.95), 590 (3.78), 649 (3.61) nm. MS (FAB) m/z 794
(M+3H)+, 793 (M+2H)+Å. Anal. Calcd for C52H33N5O4: C,
78.87; H, 4.20; N, 8.84. Found: C, 78.91; H, 4.23; N, 8.75.
´
3. (a) Tome, A. C.; Lacerda, P. S. S.; Neves, M. G. P. M. S.;
Cavaleiro, J. A. S. Chem. Commun. 1997, 1199–1200; (b)
´
Silva, A. M. G.; Tome, A. C.; Neves, M. G. P. M. S.;
Cavaleiro, J. A. S. Tetrahedron Lett. 2000, 41, 3065–
3068.

5490
S. Zhao et al. / Tetrahedron Letters 46 (2005) 5487–5490
meta,para), 8.00 (dd, 1H, Indolizine-H, J = 1.9 and
12. Selected data for compound 3: mp >300 ꢁC. 1H NMR
(300 MHz, CDCl3) d: À2.86 (s, 4H, NH), 4.27 (s, 6H,
CO2CH3), 7.64–7.73 (m, 18H, Ph-Hmeta,para), 7.99 (dd, 2H,
Indolizine-H, J = 1.9 Hz and J = 7.3 Hz), 8.07–8.15 (m,
12H, Ph-Hortho), 8.77 (AB, 8H, b-H, J = 5.2 Hz), 8.81 (d,
4H, b-H, J = 4.9 Hz), 8.93 (d, 4H, b-H, J = 4.9 Hz), 9.38
(dd, 2H, Indolizine-H, J = 0.8 and 1.9 Hz), 9.61 (dd, 2H,
Indolizine-H, J = 0.8 and 7.3 Hz). 13C NMR (75 MHz,
CDCl3) d: 52.7 (CO2CH3), 114.6, 114.7, 115.8, 117.7, 120.5,
120.9, 122.4, 123.8, 125.0, 125.9, 126.6, 127.4, 127.7, 130.2,
131.1, 131.2, 131.3, 131.4, 131.6, 134.5, 134.7, 137.5, 141.7,
141.87, 141.90, 162.2 (CO2CH3), 177.5 and 177.9 (quinone
CO). UV–vis (CHCl3) kmax (loge): 419 (5.80), 517 (4.67),
557 (4.45), 590 (4.18), 649 (4.06) nm. MS (FAB) m/z 1475
(M+H)+, 1474 M+Å. Anal. Calcd for C98H62N10O6: C,
79.77; H, 4.24; N, 9.49. Found: C, 79.86; H, 4.15; N, 9.32.
13. Vekey, K. Int. J. Mass Spectrom. Ion Processes 1990, 97,
265–282.
H
7.2 Hz), 8.21–8.24 (m, 6H, Ph-Hortho), 8.86–8.92 (m, 8H,
b-H), 9.14 (dd, 1H, Indolizine-H, J = 0.9 and 1.9 Hz), 9.87
(dd, 1H, Indolizine-H, J = 0.9 and 7.2 Hz). 13C NMR
(75 MHz, CDCl3) d: 51.7 (CO2CH3), 52.2 (CO2CH3), 53.1
(CO2CH3), 103.8, 112.1, 116.0, 120.7, 121.1, 122.4, 124.8,
125.2, 126.71, 126.74, 127.8, 131.6, 134.5, 136.7, 141.3,
141.88, 141.93, 160.7 (CO2CH3), 163.4 (CO2CH3), 166.3
(CO2CH3). UV–vis (CHCl3) kmax (loge) 417 (5.32), 516
(4.30), 553 (3.99), 590 (3.78), 646 (3.63) nm. HRMS (ESI)
Calcd for C52H38N5O6 (M+H)+: 828.2786. Found
828.2817.
17. Selected data for compound 10: mp >300 ꢁC. 1H NMR
(300 MHz, CDCl3) d: À2.77 (s, 2H, NH), 4.01 (s,
3H, CO2CH3), 7.73–7.82 (m, 11H, naphth.-H and
Ph-Hmeta,para), 8.21–8.24 (m, 6H, Ph-Hortho), 8.32–8.39
(m, 2H, naphth.-H), 8.41 (dd, 1H, Indolizine-H, J = 1.5
and 9.1 Hz), 8.87–8.94 (m, 8H, b-H), 9.01 (dd, 1H,
Indolizine-H, J = 0.9 and 9.1 Hz), 10.13 (br s, 1H,
Indolizine-H). UV–vis (CHCl3) kmax 420, 515, 551, 590,
645 nm. MS (FAB) 842 (M+H)+, 841 M+Å. HRMS (FAB)
calcd. for C56H36N5O4 (M+H)+: 842.2767. Found
842.2757.
14. Nour, T. A.; Salama, A. J. Chem. Soc. (C) 1969, 2511–
2513.
15. Selected data for compound 6: mp >300 ꢁC. 1H NMR
(300 MHz, CDCl3) d: À2.75 (s, 2H, NH), 4.24 (s, 3H,
CO2CH3), 7.72–7.80 (m, 11H, naphth.-H and
Ph-Hmeta,para), 8.10 (dd, 1H, Indolizine-H, J = 1.9 and
7.3 Hz), 8.21–8.24 (m, 7H, naphth.-H and Ph-Hortho),
8.31–8.34 (m, 1H, naphth.-H), 8.87 (AB, 4H, b-H,
J = 4.8 Hz), 8.91 (d, 2H, b-H, J = 4.9 Hz), 8.95 (d, 2H,
b-H, J = 4.9 Hz), 9.52 (dd, 1H, Indolizine-H, J = 0.9 and
1.9 Hz), 9.70 (dd, 1H, Indolizine-H, J = 0.9 and 7.3 Hz).
UV–vis (CHCl3) kmax (loge): 421 (5.54), 517 (4.33), 556
(4.10), 591 (3.84), 648 (3.73) nm. MS (FAB) 842 (M+H)+,
841 M+Å. Anal. Calcd for C56H35N5O4: C, 79.89; H, 4.19;
N, 8.32. Found: C, 79.89; H, 4.25; N, 8.32.
18. Selected data for compound 11: mp >300 ꢁC. 1H NMR
(300 MHz, CDCl3) d: À2.52 (s, 2H, NH), 4.25 (s, 3H,
CO2CH3), 6.58 (dd, 1H, naphth.-H, J = 1.0 and 7.9 Hz),
7.01 (dt, 1H, naphth.-H, J = 1.2 and 7.6 Hz), 7.35 (t, 1H,
naphth.-H, J = 7.1 Hz), 7.48 (t, 1H, Indolizine-H,
J = 7.1 Hz), 7.70–7.78 (m, 9H, Ph-Hmeta,para), 7.99–8.03
(m, 2H, Indolizine-H and naphth.-H), 8.15–8.25 (m, 6H,
Ph-Hortho), 8.64 (d, 2H, b-H, J = 4.8 Hz), 8.76 (d, 2H, b-H,
J = 4.8 Hz), 8.84 (AB, 4H, J = 5.2 Hz), 9.56 (dd, 1H,
Indolizine-H, J = 0.6 and 7.0 Hz). UV–vis (CHCl3) kmax
421, 517, 553, 593, 649 nm. MS (FAB) 842 (M+H)+, 841
M+Å. HRMS (FAB) Calcd for C56H36N5O4 (M+H)+:
842.2767. Found 842.2780.
1
16. Selected data for compound 7: mp 273–274 ꢁC. H NMR
(300 MHz, CDCl3) d: À2.76 (s, 2H, NH), 3.80, 4.05 and
4.11 (3s, 9H, 3 · CO2CH3), 7.73–7.79 (m, 9H, Ph-