Sulfolenoporphyrins: Synthons for refunctionalization of porphyrins

Article abstract of DOI:10.1016/j.tetlet.2005.01.154

Using sulfolenopyrroles (4) and (11) methods are developed for the synthesis of opp- (15,18,19) and adj- (25) bis-sulfolenoporphyrins; such compounds are useful building blocks for the refunctionalization of the porphyrin system, and readily undergo Diels

Full text of DOI:10.1016/j.tetlet.2005.01.154

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 2009–2013
Sulfolenoporphyrins: synthons for refunctionalization of porphyrins
Sang Hee Lee and Kevin M. Smith*
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
Received 17 January 2005; revised 26 January 2005; accepted 27 January 2005
Abstract—Using sulfolenopyrroles (4) and (11) methods are developed for the synthesis of opp- (15,18,19) and adj- (25) bis-sulfo-
lenoporphyrins; such compounds are useful building blocks for the refunctionalization of the porphyrin system, and readily undergo
Diels–Alder cycloaddition reactions.
Ó 2005 Elsevier Ltd. All rights reserved.
The b,b0-fused sulfolenopyrrole (1) was introduced into
pyrrole and porphyrin chemistry by Vicente et al. in
1997.1 It was shown to react thermally as a potent
masked diene with dienophiles (such as phenylvinylsulf-
one), and a new route to tetrabenzoporphyrins was
developed. These workers also cyclotetramerized the
reduction product (2) to give the symmetrical tetra-
sulfolenoporphyrin (3),1 but this was found to suffer solu-
bility problems in organic solvents. The benzyl ester (4)
of the sulfolenopyrrole was subsequently used by Gun-
ter et al.2,3 to prepare a mono-sulfolenoporphyrin (5)
using the [3+1] variant4–6 of the MacDonald synthesis,7
and this was used in Diels–Alder cycloadditions with
common dienophiles such as dimethyl acetylenedicarb-
oxylate (DMAD) and norbornadiene. Montforts and
co-workers also used pyrrole (4) to prepare an open-
chain sulfolenobilin, which was cyclized to give a sulfo-
lenochlorin and, after Diels–Alder cycloaddition, a fuller-
enochlorin.8,9 At about the same time, Kra¨utler and
co-workers synthesized the soluble zinc(II) 5,10,15,20-
tetra-aryl-tetra-sulfolenoporphyrin (6),10 and eventually
managed to accomplish stepwise Diels–Alder cycloaddi-
tions of up to four fullerenes.11
of the b,b0-fused sulfolene moiety significantly reduced
the nucleophilicity of the intermediate pyrrole, and this
is a critically important issue in pyrrole-coupling reac-
tions.12 In no case (except for the tetramerization reac-
tion of Vicente, Kra¨utler and co-workers)1,10,11 was it
found possible to prepare building blocks with more
than one sulfolenopyrrole subunit, and therefore acces-
sibility to ꢀlinearꢁ and ꢀsteppedꢁ porphyrin oligomers
and adducts was thwarted.
Gunter et al.2,3 successfully prepared symmetrical tri-
pyrranes, using the Sessler method,13 bearing either
O
O
S
O
O
S O
O
S
NH
N
N
R
N
H
HN
(1) R = CO2Et
(2) R = CH2OH
(4) R = CO2CH2Ph
O
O
S O
O
S
O
(3)
Gunter et al.2,3 successfully prepared porphyrins (e.g., 5)
bearing one sulfolenopyrrole subunit, but ambitions to
construct a library of polysulfoleno building blocks for
use in fabrication of superstructured porphyrin assem-
blies were not realized.3 The electron-withdrawing effect
O
O
O
S
Et
Ar
S O
S O
Me
H
NH
N
N
N
N
N
Zn
Ar
Ar
HN
N
Et
Keywords: Benzoporphyrin; Diels–Alder cycloaddition; Porphyrin
synthon; Sulfolenoporphyrin; Sulfolenopyrrole.
O
S O
O
S
O
Me
H
Ar
*
Corresponding author. Tel.: +1 225 578 7442; fax: +1 225 578
3458; e-mail: kmsmith@lsu.edu
(5)
(6) Ar = 3,5-di(tert-butyl)phenyl
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.154

2010
S. H. Lee, K. M. Smith / Tetrahedron Letters 46 (2005) 2009–2013
O
O
O
Et
S O
S O
S O
Me
NH HN
HN
NH HN
(8)
NH HN
O
O
HO2C
H
H
S
(7)
NH
HN
Et
HO2C
H
H
O S
O
Me
Me2NCH2
CH2NMe2
(14)
N
H
O
O
S
(13)
OHC
CHO
O
N
Et
S O
H
(9)
OHC
(11)
CHO
N
H
O
Me
S O
NH
N
N
NH
N
N
HN
O
O
Et
S
HN
O S
O
Me
(15)
low yield
O S
N
H
(10)
(12)
O
Scheme 2. Synthesis of opp-bis-sulfolenoporphyrin (15).
Scheme 1. Unsuccessful routes to opp-bis(sulfolenopyrrole)porphyrin
(12).
a viable route to the 2,5-diformylsulfolenopyrrole (11).
This was accomplished as follows: pyrrole (10) was trea-
ted with 2-isopentlyoxy-1,3-benzodithole (16)16–18 to
give a 95% yield of the bis-adduct (17).19 With HgO/
HBF4/DMSO, (17) was converted into the required
2,5-diformyl-sulfolenopyrrole (11)19 in 70% yield
(Scheme 3).
one sulfolenepyrrole in the middle (Scheme 1, 7), or two
sulfolenepyrroles, one at each end of the tripyrrane
(Scheme 1, 8). The latter was not sufficiently nucleo-
philic to react with a 2,5-diformylpyrrole (9) in the
[3+1] protocol. We have ourselves shown that sulfoleno-
pyrrole (10) does not undergo double formylation, so a
monopyrrole (11) was not available for reaction with the
mono-sulfolenopyrrole-tripyrrane (7) to give the opp-
bis(sulfolenopyrrole)porphyrin (12).
Thus, pyrrole (11) was condensed under [3+1] condi-
tions with the tripyrrane-1,14-dicarboxylic acid (14) to
give a 58% yield of the opp-bis-sulfolenoporphyrin
(18)19 (Scheme 4); this porphyrin was not particularly
soluble in common organic solvents, so the analogous
porphyrin (19)19 was also prepared from (11) and the tri-
pyrrane (20), in an unoptimized 38% yield.
Herein we report methodology that overcomes the pre-
viously identified electronic problems, and permits the
synthesis of porphyrins bearing more than one and less
than four sulfolenopyrrole subunits. We demonstrate
the effectiveness of the methodology in the synthesis of
both adj - and opp-bis(sulfoleno)porphyrins.
O
O
The standard [3+1] approach to porphyrins requires4,5 a
2,5-diformylpyrrole and a tripyrrane (as in Scheme 1).
The sulfolenopyrrole (10), is not sufficiently nucleophilic
to be formylated more than once under Vilsmeier condi-
tions, and when one electronegative formyl (or imine
salt moiety) is inserted, it certainly could not be formy-
lated a second time. Neither, in our hands, could pyrrole
(10) be 2,5-diformylated using TFA and trimethyl
orthoformate.14 In our published version of the [3+1]
route to porphyrins,6 the tripyrrane is treated with a
monopyrrole subunit bearing 2- and 5-N,N-dimethylam-
inomethylene substituents. Thus, treatment6,15 of (10)3
with an excess of Eschenmoserꢁs salt (Aldrich) gave a
50% yield of the required sulfolenopyrrole (13). This
pyrrole reacted with the tripyrrane dicarboxylic acid
(14) (Scheme 2), but only a small amount of porphyrin
(15) was obtained and this approach was abandoned.
Clearly (see Scheme 1), another avenue for success in
the synthesis of opp-bis(sulfoleno)porphyrins would be
S
H
H
N
H
S
S
O
H
(16)
(10)
AcOH, 50 ˚C, 1 h
O
O
O
O
S
S
HgO, HBF4 - DMSO
S
S
OHC
CHO
N
H
N
H
S
S
(17)
(11)
70% yield
95% yield
Scheme 3. Synthesis of 2,5-diformylsulfolenopyrrole (11).

S. H. Lee, K. M. Smith / Tetrahedron Letters 46 (2005) 2009–2013
2011
role (4) was treated with benzaldehyde in the presence
of TsOH and TFA in dichloromethane to give a 60%
yield of the dipyrromethane (21). This was catalyti-
cally denbenzylated (95% yield) to give the dipyrro-
methane 1,9-dicarboxylic acid (22). Compound (22)
was treated with the generic 1,9-diformyldipyrro-
methane (23) [obtained by the reaction of 3,5-dimeth-
oxybenzaldehyde with pyrrole {40% yield of 1,9-di-
unsubstituted dipyrromethane (24)} followed by
double Vilsmeier formylation (70% yield)] to give
porphyrin (25)19 in 15% yield (Scheme 5).
O
R
S O
Me
NH HN
HN
O
O
S
HO2C
R
HO2C
OHC
CHO
N
H
Me
(11)
(14) R = Et
(20) R = CH2CH2CO2Me
O
R
S O
Finally, susceptibility of the opp- (18,19) and adj-bis-sul-
folenoporphyrins (25) toward Diels–Alder cycloaddition
reactions was readily established. For example (Scheme
6), the opp-porphyrin (18) reacted (at 110 °C in tri-
chlorobenzene) with DMAD to give the bis-adduct
(26). With DDQ this gave an overall 85% yield [from
(18)] of the opp-dibenzoporphyrin (27).19 As was pre-
dictable based on steric arguments, Diels–Alder cyclo-
addition reactions of the adj-bis-sulfolenoporphyrin
(25) were more difficult to accomplish. With DMAD
at 214 °C in trichlorobenzene, the bis-adduct (28) was
obtained, and after DDQ treatment, a 40% overall yield
[from (25)] of the adj-dibenzoporphyrin (29)19 was
obtained.
Me
NH
N
N
HN
R
O S
O
Me
(18) R = Et (58% yield)
(19) R = CH2CH2CO2Me (38%)
Scheme 4. Synthesis of opp-bis-sulfolenoporphyrins (18) and (19).
Our attention next turned to methodology for synthe-
sis of an adj-bis-sulfolenoporphyrin. The sulfolenopyr-
O
O
O
O
S
S O
O S
CHO
NH HN
(21)
TsOH/TFA
CO2CH2Ph
N
H
PhCH2O2C
CO2CH2Ph
(4)
O
O
S O
O S
O
O
O S
S O
NH HN
(22)
+
HO2C
OHC
CO2H
NH
N
N
TFA/CH2Cl2
HN
CHO
NH HN
(25)
MeO
OMe
MeO
OMe
(23)
MeO
OMe
H
H
NH HN
CHO
TFA
N
H
MeO
OMe
(24)
Scheme 5. Synthesis of adj-bis-sulfolenoporphyrin (25).

2012
S. H. Lee, K. M. Smith / Tetrahedron Letters 46 (2005) 2009–2013
(18)
(25)
DMAD, heat
DMAD, heat
CO2Me
CO2Me
MeO2C
MeO C
CO2Me
CO2Me
Et
2
Me
NH
N
N
NH
N
HN
N
HN
Et
MeO2C
MeO2C
Me
(28)
(26)
MeO
OMe
DDQ
DDQ
CO2Me
Et
CO2Me
CO2Me
CO2Me
MeO2C
MeO2C
Me
NH
N
N
NH
N
N
HN
Et
HN
MeO2C
MeO2C
Me
(27)
(29)
MeO
OMe
Scheme 6. Diels–Alder cycloaddition reactions of (18) and (25).
12. Smith, K. M.; Vicente, M. G. H. In Science of Synthesis;
Weinreb, S. M., Ed.; Thieme: Stuttgart, 2004; Vol. 17, pp
1087–1116.
13. Sessler, J. L.; Johnson, M. R.; Lynch, V. J. Org. Chem.
1987, 52, 4394–4397.
Acknowledgements
This work was supported by grants from the National
Science Foundation (CHE-0296012) and the National
Institutes of Health (EB-002064).
14. Tardieux, C.; Bolze, F.; Gros, C. P.; Guilard, R. Synthesis
1998, 267–268.
15. Nguyen, L. T.; Senge, M. O.; Smith, K. M. Tetrahedron
Lett. 1994, 35, 7581–7584.
References and notes
16. Nakayama, J. J. Chem. Soc., Perkin Trans. 1 1975, 525–
530.
17. Nakayama, J.; Imura, M.; Hoshino, M. Chem. Lett. 1975,
1319–1320.
18. Cadamuro, S.; Degani, I.; Fochi, R.; Gatti, A.; Piscopo,
1. Vicente, M. G. H.; Tome, A. C.; Walter, A.; Cavaleiro, J.
A. S. Tetrahedron Lett. 1997, 38, 3639–3642.
2. Gunter, M. J.; Tang, H.; Warrener, R. N. Chem. Commun.
1999, 803–804.
3. Gunter, M. J.; Tang, H.; Warrener, R. N. J. Porphyrins
Phthalocyanines 2002, 6, 673–684.
4. Boudif, A.; Momenteau, M. J. Chem. Soc., Perkin Trans.
1 1996, 1235–1242.
5. Lash, T. D. In The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic: San Diego,
2000; Vol. 2, pp 125–199.
6. Nguyen, L. T.; Senge, M. O.; Smith, K. M. J. Org. Chem.
1996, 61, 998–1003.
7. Arsenault, G. P.; Bullock, E.; MacDonald, S. F. J. Am.
Chem. Soc. 1960, 82, 4384–4389.
8. Montforts, F.-P.; Kutzki, O. Angew. Chem., Int. Ed. 2000,
39, 599–601.
9. Kutzki, O.; Walter, A.; Montforts, F.-P. Helv. Chim. Acta
2000, 83, 2231–2245.
L. J. Chem. Soc., Perkin Trans. 1 1993, 2939–
2943.
19. Selected data for 11: 1H NMR (DMSO-d6), d ppm: 4.48 (s,
4H), 9.76 (s, 2H); 13C NMR (DMSO-d6), d ppm 52.2,
123.0, 130.0, 181.7; HRMS (TOF ES+): Calcd for
C8H7NO4 M+Na = 235.9993, found: m/z 235.9986; Anal.
Calcd for C8H7NO4SÆ0.25H2O: C, 44.13; H, 3.47; N, 6.43.
Found: C, 44.20; H, 3.44; N, 6.21.
Selected data for 17: 1H NMR (CDCl3), d ppm 3.85 (s,
4H), 6.39 (d, J = 6.6 Hz, 2H), 7.12 (m, 4H), 7.35 (m, 4H),
11.43 (s, 1H); 13C NMR (CDCl3) d 47.5, 52.6, 112.5, 122.3,
125.6, 126.0, 136.5; HRMS (TOF ES+): Calcd for
C20H15NO2S5 M+Na = 483.9604, found: m/z 483.9603;
Anal. Calcd for C20H15NO2S5: C, 52.04; H, 3.28; N, 3.03.
Found: C, 51.97; H, 3.35; N, 2.96.
10. Kra¨utler, B.; Sheehan, C. S.; Rieder, A. Helv. Chim. Acta
2000, 83, 583–591.
11. Rieder, A.; Kra¨utler, B. J. Am. Chem. Soc. 2000, 122,
9050–9051.
Selected data for 18: UV–vis kmax (CH2Cl2) 399 nm (e
360,000), 503 (36,000), 541 (39,000), 562 (32,000); 1H
NMR (CDCl3+TFA), d ppm ꢀ3.00 (br, 2H), 1.64 (t,
J = 9.2 Hz, 3H), 3.58 (s, 3H), 4.04 (q, J = 9.2 Hz, 2H), 5.68

S. H. Lee, K. M. Smith / Tetrahedron Letters 46 (2005) 2009–2013
2013
(s, 4H), 5.69 (s, 4H), 10.63 (2, 2H), 10.65 (s, 2H); 13C
NMR (CDCl3+TFA), d ppm 11.9, 16.4, 20.2, 55.7, 101.0,
101.4, 107.3, 111.8, 116.4, 134.6, 137.7, 139.5, 143.1, 143.9,
146.0, 153.1, 158.9, 159.6; HRMS (TOF ES+): Calcd for
C30H30N4O4S2 M+H = 575.1786, found: m/z 575.1786.
Selected data for 19: UV–vis kmax (CH2Cl2) 401 nm (e
149,000), 504 (25,800), 543 (25,800); 1H NMR
Selected data for 27: UV–vis kmax (CH2Cl2) 419 nm (e
500,000), 497 (31,500), 567 (84,800), 581 (63,600), 636
(34,800); 1H NMR (CDCl3), d ppm ꢀ6.73 (s, 2H), 1.58 (s,
6H), 1.66 (t, J = 7.6 Hz, 6H), 3.22 (s, 6H), 3.71 (q,
J = 7.6 Hz, 4H), 4.33 (s, 6H), 4.34 (s, 6H), 9.13 (s, 4H),
9.28 (s, 2H), 9.34 (s, 2H); 13C NMR (CDCl3) d ppm 11.1,
17.5, 19.4, 53.4, 53.6, 94.5, 94.6, 121.5, 121.7, 130.1, 130.2,
132.5, 134.5, 135.3, 139.4, 141.5, 141.7, 146.1, 146.2, 169.4,
169.5; HRMS (TOF ES+): Calcd for C42H38N4O8+
H = 749.2587, found: m/z 749.2579; Anal. Calcd for
C42H38N4O8Æ1.5H2O: C, 68.57; H, 5.34; N, 7.61. found:
C, 68.31; H, 5.38; N, 7.41.
(CDCl3+TFA),
d
ppm ꢀ3.50 (br, 2H), 3.16 (t,
J = 7.3 Hz, 4H), 3.67 (s, 6H), 3.68 (s, 6H), 4.46 (t,
J = 7.3 Hz, 4H), 5.75 (s, 4H), 5.81 (s, 4H), 10.66 (s, 2H),
10.90 (s, 2H); 13C NMR (CDCl3+TFA), ppm 11.7, 21.7,
29.9, 30.6, 35.4, 53.4, 56.0, 102.0, 102.2, 135.1, 135.6,
137.7, 138.1, 142.0, 143.3, 176.2.
Selected data for 29: UV–vis kmax (CH2Cl2) 431 nm (e
440,000), 534 (37,600), 569 (50,900), 594 (33,000), 650
Selected data for 25: UV–vis kmax (CH2Cl2) 408 nm (e
1
1
106,000), 502 (11,300), 576 (7000); H NMR (CDCl3), d
(28,000). H NMR (CDCl3) d ppm ꢀ2.45 (s, 1H), ꢀ2.22
ppm ꢀ3.22 (s, 2H), 4.01 (s, 6H), 4.51 (s, 4H), 5.63 (s, 4H),
6.95 (s, 1H), 7.42 (d, J = 2.2 Hz, 2H), 7.85–8.00 (m, 5H),
9.20 (d, J = 4.7 Hz, 2H), 9.38 (d, J = 4.7 Hz, 2H), 10.12 (s,
2H); 13C NMR (CH2Cl2), d ppm 55.9, 56.2, 58.7, 100.6,
104.1, 114.7, 118.2, 121.1, 129.2, 130.5, 132.4, 132.6, 133.0,
135.0, 136.7, 139.4, 140.0, 141.3, 142.8, 146.3, 148.9, 160.0;
HRMS (TOF ES+): Calcd for C38H31N4O8S2Mꢀ
2SO2+H = 575.2447, found: m/z 575.2231; Anal. Calcd
for C38H30N4O6S2Æ1.5H2O: C, 62.55; H, 4.55; N, 7.67.
Found: C, 62.65; H, 4.35; N, 7.51.
(br s, 1H), 4.02 (s, 6H), 4.04 (s, 6H), 4.20 (s, 6H), 6.97 (t,
J = 2.0 Hz, 1H), 7.46 (d, J = 2.0 Hz, 2H), 7.49 (s, 2H),
7.64–7.72 (m, 4H), 7.98 (t, J = 6.1 Hz, 1H), 9.11 (d,
J = 4.6 Hz, 2H), 9.24 (d, J = 4.6 Hz, 2H), 9.67 (s, 2H),
10.37 (s, 2H). 13C NMR (CDCl3) d ppm 52.9, 53.3, 55.9,
100.3, 114.1, 114.6, 122.0, 127.0, 128.8, 129.1, 129.8, 130.9,
131.1, 131.2, 132.3, 137.3, 138.4, 139.3, 140.1, 141.9,
145.1,146.5, 159.6, 168.2, 169.0. HRMS (TOF ES+):
Calcd for C50H39N4O10 M+H = 855.2666, found: m/z
855.2595.