Porphodimethylidenes from porphyrin-fused 3-sulfolenes - Versatile porphyrin dienes for cycloadditions

Article abstract of DOI:10.1039/a901446b

A porphyrin with a β-fused 3-sulfolene on one of the pyrroles acts as a porphodimethylidene precusor which can be used for a variety of Diels-Alder cycloaddition reactions.

Full text of DOI:10.1039/a901446b

Porphodimethylidenes from porphyrin-fused 3-sulfolenes—versatile porphyrin
dienes for cycloadditions
Maxwell J. Gunter,*a Hesheng Tanga and Ronald N. Warrenerb
a Division of Chemistry, University of New England, Armidale, NSW 2351, Australia.
E-mail: mgunter@metz.une.edu.au
b Centre for Molecular Architecture, Central Queensland University, Rockhampton, Queensland 4702, Australia
Received (in Cambridge, UK) 22nd February 1999, Accepted 26th March 1999
A porphyrin with a b-fused 3-sulfolene on one of the pyrroles
acts as a porphodimethylidene precusor which can be used
for a variety of Diels–Alder cycloaddition reactions.
clay, CH2Cl2, room temperature, 10 h) with benzyl 5-acetoxy-
methyl-4-ethyl-3-methylpyrrole-2-carboxylate resulted in the
tripyrrane 4, which was subsequently hydrogenolysed and
subjected to a ‘3 + 1’ porphyrin synthesis15 with pyrrole-
2,5-dicarbaldehyde (TFA, CH2Cl2, room temperature, 2 h,
followed by DDQ, 1 h) to form the desired porphyrin 5.†
While 5 is indefinitely stable at ambient temperatures, on
heating above 80 °C it readily loses SO2 to form the reactive
porphodimethylidene 6. Although it was not possible to isolate
6, it could be trapped as Diels–Alder adducts in the presence of
suitable dienophiles. In the absence of a dienophile and at
moderate temperatures (80–110 °C, toluene) it cleanly pro-
duced the dimer 7.
The need for molecular assemblies that will match the
increasingly sophisticated design demands of supramolecular
chemistry has been the motive for the production of modular
components that can be assembled readily and predictably. This
is especially so for custom-designed porphyrins which can be
utilised in an impressive variety of systems.1
For some applications it has been necessary to constrain
rotational freedom of the porphyrin nucleus within the assem-
bly, and this has most effectively been achieved by a 1,2-linkage
at adjacent b-pyrrole positions. Hence the construction of many
rigid porphyrin-containing systems has commonly utilised
Schiff base formation with preformed porphyrin diamines or
diones.2 However, the Diels–Alder reaction is a classic
cycloaddition reaction which leads to fused ring systems and is
ideally suited to the construction of well-defined molecular
assemblies with limited flexibilities.
There have been few reports of Diels–Alder chemistry
involving porphyrins and related macrocycles. Of these, several
have used b-vinyl porphyrins as the diene,3 and a related
tetramethine-bridged porphyrin has also been shown to undergo
cycloaddition reactions.4 Alternatively, tetraaryl porphyrins
have been used as dienophiles, giving a mixture of products
with reactive dienes under forcing conditions,5 and Diels-Alder
methodology has been used in the construction of benzopor-
phyrins.6 More recently, N-substituted b-fused pyrroloporphyr-
ins have been used as dienes for certain cycloaddition
reactions.7 We have shown that cycloaddition reactions provide
an excellent method for geometric control in certain made-to-
order rigid assemblies which incorporate porphyrins.8
Aromatic fused 3-sulfolenes have been used as precursors for
highly reactive o-quinodimethanes.9 Thermal extrusion of
sulfur dioxide from the sulfolenes is usually performed in the
presence of a dienophile so that the quinodimethane is trapped
as a Diels–Alder adduct.10 While N-substituted pyrrole-fused
3-sulfolenes have been used as a source of annelated pyrroles,11
some of which have been subsequently used in the synthesis of
pyrroloporphyrins12 and symmetrical tetra-substituted porphyr-
ins,6 reported here is the first example to the best of our
knowledge of a porphyrin with a b-fused sulfolene that allows
subsequent chemistry at only one of the pyrroles. This is a key
precusor for a range of cycloadducts resulting from Diels–Alder
reaction of the intermediate porphodimethylidene which is
formed by elimination of sulfur dioxide under mild condi-
tions.
Compound 7 is analogous to the previously identified dimeric
product formed from o-quinodimethane itself,9 and its structure
was established from its 1H NMR spectrum and mass spectrum
[m/z 841.5 (M + H)+]. In particular the NMR spectrum (C6D6)
showed a clear lack of simple symmetry, and individual
O2
S
O2
S
i
SO2Ph
R1
R2
N
H
1 R1 = H, R2 = CO2Bn (37%)
2 R1, R2 = I (75%)
3 R1, R2 = H (78%)
ii
iii
+
3
iv
CO2Bn
N
H
AcO
BnO2C
BnO2C
N
H
HN
SO2
H
N
v
N
H
N
SO2
N
4
H
N
(57%)
The pyrrole-fused 3-sulfolene 1 was prepared by a modifica-
5
tion of the Barton–Zard reaction13 using benzyl isocyanoacetate
(55%)
and
3-phenylsulfonyl-2,5-dihydrothiophene
1,1-dioxide
Scheme 1 Reagents and conditions: i, NCCH2CO2Bn, KOBut, THF,
215–25 °C, 2 h; ii, H2, Pd–C (10%), 3 atm, 7 h, room temp., then I2, KI(aq.
EtOH), 5 h, room temp.; iii H2, Pd–C (10%), NaOAc, 3 atm, 22 h, room
temp.; iv, Montmorillonite clay K-10, CH2Cl2, N2, 10 h, room temp.; v, H2,
Pd–C (10%), 3 atm, 3 h, then pyrrole-2,5-dicarbaldehyde, TFA, CH2Cl2, 2
h, then DDQ, 1 h, room temp.
(Scheme 1),14 in an analogous manner to that for the
corresponding ethyl ester reported by Vicente et al.6 Hydro-
genolysis (H2, 10% Pd–C) and oxidative iodination (I32, room
temperature, 2 h) to give 2 followed by reduction (H2, 10% Pd–
C, NaOAc, 3 atm) produced 3. Condensation (Montmorillonite
Chem. Commun., 1999, 803–804
803

5
[2H, s, pyrrole b-H], 9.87 [2H, s, meso-H], 10.21 [2H, s, meso-H];
lmax(CHCl3)/nm 392, 502, 539, 561; nmax/cm21 1216(SNO); m/z (FAB)
485.20074 (M+ + 1). For 7: dH(300 MHz, C6D6, dashed (A) numbering for
chlorin ring) 21.62 [2H, br s, NAH], 22.76 [2H, s, NH], 0.82 [3H, t,
C(7A)CH2CH3], 1.67 [3H, t, C(18A)CH2CH3], 1.76 [3H, t, C(13)CH2CH3],
1.95 [3H, t, C(2)CH2CH3], 2.93 [3H, s, C(8A)CH3], 3.28 [3H, s, C(17A)CH3],
3.34 [3H, s, C(12)CH3], 3.48 [3H, s, C(3)CH3], 2.83 [2H, m,
C(7A)CH2CH3], 3.05 [1H, m, C(22A)CH2], 3.34 [1H, m, C(22A)CH2], 3.84
[4H, m, C(18A, 13)CH2CH3], 4.11 [2H, m, C(2)CH2CH3], 4.68 [2H, m,
C(21)CH2CH2], 5.18 [1H, d, J 21, C(23) CH2], 5.56 [1H, d, J 21, C(23)
CH2], 6.16 [1H, s, C(3A)NCH2], 6.95 [1H, s, C(3A)NCH2], 9.21 [1H, d,
C(7)H], 9.23 [1H, d, C(12A)H], 9.45 [1H, d, C(8)H], 9.46 [1H, d, C(13A)H],
9.50. 9.75, 9.80, 9.87, 10.20, 10.27, 10.38, 10.48 [1H each, s, meso-HAs]; m/z
(FAB) 841.47036 (M++1). For 8: dH(CDCl3) 24.01 [2H, br s, NH], 1.86
[6H, t, CH2CH3], 3.68 [6H, s, CH3], 4.08 [6H, s, OCH3], 4.12 [4H, q,
CH2CH3], 5.10 [4H, s, CH2], 9.36 [2H, s, pyrrole b-H], 9.93 [2H, s, meso-
H], 10.17 [2H, s, meso-H]; m/z (EI) 562.25886 (M+). For 9: dH(CDCl3)
23.95 [2H, br s, NH], 1.88 [6H, t, CH2CH3], 3.68 [6H, s, CH3], 4.15 [6H,
m, CH2CH3, CH], 4.30, 4.36 [2H, m, CH2], 4.84 [2H, d, CH2A], 6.86 [2H,
m, Ar–H], 7.10 [3H, m, Ar–H], 9.38 [2H, s, pyrrole b-H], 10.11 [2H, s,
meso-H], 10.19 [2H, s, meso-H]; m/z (EI) 593.27971 (M+). For 10:
dH(CDCl3) 23.90 [2H, br s, NH], 1.84 [6H, t, CH2CH3], 1.86 [1H, d, J 10,
CH2], 2.35 [1H, d, J 10, CH2], 2.57 2H, m, CH], 3.13 [2H, s, CH], 3.45 [2H,
dd, CH2], 3.64 [6H, s, CH3], 4.12 [4H, q, CH2CH3], 4.69 [2H, dd, CH2],
6.38 [2H, s, NCH], 9.40 [2H, s, pyrrole b-H], 10.09 [2H, s, meso-H], 10.18
[2H, s, meso-H].
CO2Me
CO2Me
N
ii
N
H
8
N
N
H
N
iii
O
N
N
Ph
6
O
iv
9
i
N
H
N
N
N
H
N
N
10
HN
NH
N
1 See, for example Comprehensive Supramolecular Chemistry, ed. J. L.
Atwood, J. E. D. Davies, D. D. MacNicol and F. Vogtle, Elsevier,
Oxford, 1996, vol. 2, 4, 5, 6, 9, 10.
7
Scheme 2 Reagents and conditions: i, D, toluene, 80–110 °C, 2 h; ii,
MeO2CC·CCO2Me, D, toluene, 110 °C, 4.5 h; iii, N-phenylmaleimide, D,
85 °C, 3 h; iv, norbornadiene, D, 80 °C, 2 h.
2 M. J. Crossley, L. G. King, I. A. Newsom and C. S. Sheehan, J. Chem.
Soc., Perkin Trans. 1, 1996, 2675; M. J. Crossley and J. K. Prashar,
Tetrahedron Lett., 1997, 38, 6751; M. J. Crossley, L. J. Govenlock and
J. K. Prashar, J. Chem. Soc., Chem. Commun., 1995, 2379; M. J.
Crossley, P. L. Burn, S. J. Langford and J. K. Prashar, J. Chem. Soc.,
Chem. Commun., 1995, 1921; E. J. Atkinson, A. M. Oliver and M. N.
Paddon-Row, Tetrahedron Lett., 1993, 34, 6147; P. T. Gulyas, S. J.
Langford, N. L. Lokan, M. G. Ranasinghe and M. N. Paddon-Row,
J. Org. Chem., 1997, 62, 3038; K. A. Jolliffe, T. D. M. Bell, K. P.
Ghiggino, S. J. Langford and M. N. Paddon-Row, Angew. Chem., Int.
Ed., 1998, 37, 916.
3 M. A. F. Faustino, M. G. P. M. S. Neves, M. G. H. Vicente, A. M. S.
Silva and J. A. S. Cavaleiro, Tetrahedron Lett., 1996, 37, 3569; S. Kai
and M. Suzuki, Tetrahedron Lett., 1996, 37, 5931; G. Zheng, A. N.
Kozyrev, T. J. Dougherty, K. M. Smith and R. K. Pandey, Chem. Lett.,
1996, 1119.
resonances for each of the substituents on the porphyrin and
chlorin rings.† For example, there are four distinct ethyl and
methyl resonances, two AB quartets for the b-pyrrole protons,
eight singlets for the meso-protons, and two NH singlets at high
field. The exocyclic methylene is defined by two singlets (d
6.16 and 6.95) significantly deshielded by the neighbouring
porphyrin while the deshielded single bridging methylene is a
clear AB quartet at d 5.18 and 5.56. The remaining ethylene of
the spiro-linked cyclohexene bridge is a series of complex
multiplets at d 3.05, 3.34 and 4.68. The UV-visible spectrum of
7 is a composite of both porphyrin and chlorin-type rings and
not surprisingly shows little evidence of electronic communica-
tion between the linked macrocycles.
4 P. A. Liddell, L. J. Demanche, S. Li, A. N. Macpherson, R. A. Nieman,
A. L. Moore, T. A. Moore and D. Gust, Tetrahedron Lett., 1994, 35,
995.
On heating 5 in toluene at 80–110 °C in the presence of
various dienophiles shown in Scheme 2, the corresponding
Diels–Alder adducts were isolated in good yields (65–95%).†
5 A. C. Tomé, P. S. S. Lacerda, M. G. P. M. S. Neves and J. A. S.
Cavaleiro, Chem. Commun., 1997, 1199.
6 S. Ito, T. Murashima and N. Ono, J. Chem. Soc., Perkin Trans. 1, 1997,
3161; S. Ito, T. Murashima, H. Uno and N. Ono, Chem. Commun., 1998,
1661; M. G. H. Vicente, A. C. Tomé, A. Walter and J. A. S. Cavaleiro,
Tetrahedron Lett., 1997, 38, 3639.
7 S. Knapp, J. Vasudevan, T. J. Emge, B. H. Arison, J. A. Potenza and
H. J. Schugar, Angew. Chem., Int. Ed., 1998, 37, 2368.
8 R. N. Warrener, A. C. Schultz, M. R. Johnston and M. J. Gunter, J. Org.
Chem., 1999, in press; R. N. Warrener, M. R. Johnston and M. J. Gunter,
Synlett, 1998, 593; R. N. Warrener, M. R. Johnston, A. C. Schultz, M.
Golic, M. A. Houghton, M. J. Gunter and R. A. Russell, Synlett, 1998,
590.
9 J. L. Charlton and M. M. Alauddin, Tetrahedron (Tetrahedron Report
No. 220), 1987, 43, 2873; T.-S. Chou, Rev. Heteroatom Chem., 1993, 8,
65.
10 H.-C. Chen and T.-S. Chou, Tetrahedron, 1998, 54, 12609.
11 K. Ando, M. Kankake, T. Suzuki and H. Takayama, Synlett, 1994,
741.
12 M. G. H. Vicente, M. T. Cancilla, C. B. Lebrilla and K. M. Smith, Chem.
Commun., 1998, 2355.
13 D. Barton and S. Zard, J. Chem. Soc., Chem. Commun., 1985, 1098; D.
Barton, J. Kertvagoret and S. Zard, Tetrahedron, 1990, 46, 7587; D. P.
Arnold, L. Burgess-Dean, J. Hubbard and M. A. Rahman, Aust. J.
Chem., 1994, 47, 969.
The C2 symmetry of each is clear from the 1H NMR spectra. In
v
the case of 10, only a single stereoisomer was isolated, and both
a lack of vicinal H, H-coupling and no significant shielding of
the ethylenic protons indicates it to be the exo-product
(molecular modelling indicates a close proximity of the
ethylenic protons to the shielding region of the porphyrin in the
endo-isomer, although the environments of the bridge methy-
lenes are little different in either isomer). Each of these suggests
considerable potential as building blocks for higher level
structures. For example 8 can be utilised in further cycloaddi-
tion reactions using its activated double bond, 9 via a variety of
associated N-substituted derivatives can provide a single
attachment point on a meso-unsubstituted porphyrin, and the
formation of 10 indicates the possibility for more elaborate
architectures. Although these few reactions demonstrate the
utility of 5, its potential is clearly much more extensive and can
now be explored.
This research was supported by the Australian Research
Council.
14 P. Hopkins and P. Fuchs, J. Org. Chem., 1978, 43, 1208; S.-S. Chou and
C. M. Sun, Tetrahedron Lett., 1990, 31, 1035.
15 T. D. Lash, Chem. Eur. J., 1996, 2, 1197.
Notes and references
† Selected data for 5: dH(CDCl3) 24.0 [2H, br s, NH], 1.84 [6H, t,
CH2CH3], 3.70 [6H, s, CH3], 4.12 [4H, q, CH2CH3], 5.67 [4H, s, CH2], 9.38
Communication 9/01446B
804
Chem. Commun., 1999, 803–804