A general approach to L-tyrosine porphyrins

Article abstract of DOI:10.1016/S0040-4020(03)00487-3

A novel and general approach has been developed to prepare L-tyrosine-containing porphyrins. The key intermediates, 2-tert-butoxycarbonylamino-3-(3-formyl-4-hexyloxy-phenyl)-propionic acid hexyl ester and 2-tert-butoxycarbonylamino-3-(3-formyl-4-methoxy-phenyl)-propionic acid methyl ester, were prepared by the Reimer-Tiemann reaction of Boc-protected L-tyrosine, which was followed by esterification and alkylation of the phenol hydroxide. A number of novel chiral L-tyrosine porphyrins were obtained from the reactions of 2-tert-butoxycarbonylamino-3-(3-formyl-4-alkoxy-phenyl)-propionic acid ester with different dipyrrolylmethanes and the reaction of 5-(4-trifluoromethylphenyl)pyrromethane afforded the highest yield. The tyrosine porphyrins could be readily deprotected to afford the corresponding diacid or diamine derivatives.

Full text of DOI:10.1016/S0040-4020(03)00487-3

Tetrahedron 59 (2003) 3505–3510
A general approach to L-tyrosine porphyrins
*
Hong Chen, Xue-Bin Shao, Xi-Kui Jiang and Zhan-Ting Li
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Received 6 November 2002; revised 28 February 2003; accepted 20 March 2003
Abstract—A novel and general approach has been developed to prepare L-tyrosine-containing porphyrins. The key intermediates, 2-tert-
butoxycarbonylamino-3-(3-formyl-4-hexyloxy-phenyl)-propionic acid hexyl ester and 2-tert-butoxycarbonylamino-3-(3-formyl-4-meth-
oxy-phenyl)-propionic acid methyl ester, were prepared by the Reimer–Tiemann reaction of Boc-protected L-tyrosine, which was followed
by esterification and alkylation of the phenol hydroxide. A number of novel chiral L-tyrosine porphyrins were obtained from the reactions of
2-tert-butoxycarbonylamino-3-(3-formyl-4-alkoxy-phenyl)-propionic acid ester with different dipyrrolylmethanes and the reaction of 5-(4-
trifluoromethylphenyl)pyrromethane afforded the highest yield. The tyrosine porphyrins could be readily deprotected to afford the
corresponding diacid or diamine derivatives. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
linkers.14–16 Therefore, the possibility of synthesizing
porphyrin derivatives from natural L-tyrosine was explored.
Porphyrins are one of the most useful frameworks for
artificial receptors and catalysts because of their unique
features, such as large rigid and planar conjugated
structures, strong metal coordination activity, extensive
We chose the well-established Lindsey method, which
involves the condensation of an aldehyde with a dipyr-
rolylphenylmethane, followed by an oxidation process, to
synthesize tyrosine porphyrins. Thus, aldehyde 2 was first
prepared according to a reported method,17 which was then
converted into compounds 3a,b. The phenol hydroxy group
was alkylated in order to improve the solubility of the
modifiability, and plentiful photophysical properties.1–5
A
large number of achiral porphyrin derivatives have been
synthesized for the purpose of molecular recognition
and self-assembly.6–12 In contrast, examples of chiral
porphyrins as recognition or assembling blocks are
remarkably limited.13–16 We herein report one facile and
general method to prepare chiral porphyrin derivatives by
directly introducing two or four natural L-tyrosine units to
the meso positions of porphyrins. Considering that the
amino and acid groups of the new porphyrin derivatives
may be readily modified, the chiral porphyrin derivatives
developed in this paper are expected to be used as new
building blocks for future chiral supramolecular design and
synthesis.
1
resulting compounds in organic solvents (Scheme 1). H
NMR spectra exhibit one set of well-established signals,
indicating that the alkylation of the phenol hydroxyl groups
did not lead to the formation of cis/trans atropisomers.18,19
Since the formation of the porphyrin skeleton by the
reactions of aldehydes and dipyrrolylphenylmethanes is
usually of low yields, it is necessary to explore the effect of
2. Results and discussion
We recently initiated a new project of porphyrin-based
molecular recognition, which requires that two chiral amino
acid or short peptide units are connected to a porphyrin
skeleton as closely as possible. Reported methods could not
meet our requirement because in all the reported cases
amino acid or peptide groups are connected by additional
Keywords: porphyrin; L-tyrosine; synthesis; Reimer–Tiemann reaction.
*
Corresponding author. Tel.: þ86-21-6416-3300; fax: þ86-21-6416-6128;
e-mail: ztli@pub.sioc.ac.cn
Scheme 1. Synthesis of 3a,b.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00487-3

3506
H. Chen et al. / Tetrahedron 59 (2003) 3505–3510
Scheme 2. Synthesis of 5a–e.
different substituents at the benzene p-position on the yields
of the corresponding reactions to prepare porphyrin
derivatives and find the most suitable dipyrrolylmethane
intermediates. Therefore, a series of dipyrrolylmethanes
5a–e were synthesized from the reactions of aldehydes 4a–
e and pyrrole in the presence of trifluoroacetic acid (TFA) or
boron trifluoride (Scheme 2).
Several different condensation conditions were explored in
order to find the optimal conditions for the reactions of
compounds 3 and 5. Using toluenesulfonic acid and
propionic acid as catalysts at high temperature was not
suitable for any of the present reactions: no expected
porphyrin derivatives could be obtained from the reactions
with these two acids as catalysts.20,21 Trifluoroacetic acid
(Method A) and boron trifluoride (Method B) could catalyze
the reactions, but the yields of the reactions were
substantially dependent on the substituents of compounds
5a–e. The reaction conditions and yields obtained from
these compounds are shown in Scheme 3.
The highest yield (32%) of the porphyrin derivative was
obtained from the reaction of compounds 3b and 5e by using
Method B. Most other reactions afforded moderate yields of
the expected porphyrins (6–16%). Generally, the existence
of electron-withdrawing groups in intermediates 5 is helpful
for the formation of porphyrins 6, since it was found that,
under the similar conditions, the reaction of 3a,b with 5a,
which bears the electron donating hexyloxy group, only led
to the formation of trace amounts of the expected porphyrin
products, as indicated by the MS spectra. Rearrangement
products 7a–c and 8 were also separated from the reactions
of compound 3a and the corresponding dipyrrolylmethanes
5.22–24
Porphyrin 9, which bears four tyrosine units, was also
generated albeit in the relatively low yield of 6% for the
reaction of compound 3b with pyrrole in the presence of
boron trifluoride (Scheme 4). The product has been fully
characterized by 1H NMR spectroscopy, and electron spray
mass spectrometry.
De-protection of porphyrin 6e was explored as a typical
example. With trifluoroacetic acid as the de-protection
reagent, compound 10 was obtained in quantitative yield.
With lithium hydroxide, diacid 11 was obtained in 86%
yield. In principle, these tyrosine porphyrins may be further
modified, to produce different chiral porphyrin derivatives.
The formation of the porphyrin skeletons is usually affected
by the existence of strong Lewis acids. The Boc protecting
Scheme 3. Synthesis of porphyrins 6.

H. Chen et al. / Tetrahedron 59 (2003) 3505–3510
3507
Scheme 4.
group of the tyrosine amino might be unstable during the
reactions. This may be partly responsible for the reduced
yields of some of the tyrosine porphyrins. Therefore, the
reactions of simple methyl ester of L-tyrosine 12 with
intermediates 5 were also explored. However, no expected
tyrosine porphyrin products could be obtained under the
above conditions, indicating that the protection of the amino
group is necessary. Treatment of tyrosine derivatives with
the acid group unprotected with 5 in the presence of
trifluoroacetic acid or boron trifluoride led to formation of
the expected porphyrin products in remarkably low yields
(ca. 2%). These results indicate that protection of the amino
and acid group in the starting materials are necessary for
efficient formation of the porphyrin skeleton.
Elemental analysis was carried out at the SIOC analytical
center. Unless stated otherwise, all reagents and chemical
were obtained from commercial sources and used without
further purification. Pyrrole was distilled from calcium
hydride, dichloromethane and chloroform from calcium
hydride or phosphorus pentoxide, acetonitrile from phos-
phorus pentoxide. Silica gel (300–400 mesh) was used for
column chromatography. Compounds 1,25 4a,26 5a,27 5c,28
5d,29 and 5e30 were prepared according to reported
methods.
3. Conclusion
We have developed one general and efficient method to
prepare L-tyrosine porphyrin derivatives, starting from
various aldehyde derivatives of the amino- and acid-
protected tyrosines. The effects of the substituents and
reaction conditions on the yields of the reactions have been
investigated. Considering the ready availability of the
corresponding tyrosine intermediates and the simple reac-
tion conditions used in this work, it is expected that the new
porphyrin derivatives developed here may be used as
starting materials for further new chiral porphyrin systems.
Further work of molecular recognition based on the tyrosine
porphyrins reported in this paper is being carried out.
4.1.1. 2-tert-Butoxycarbonylamino-3-(3-formyl-4-hexyl-
oxy-phenyl)-propionic acid hexyl ester 3a. A mixture of
compound 2 (1.69 g, 5.47 mmol), potassium carbonate
(1.51 g, 10.9 mmol) and 1-bromohexane (1.54 mL,
10.9 mmol) in DMF (50 mL) was heated at 808C with
stirring for 1 h and then cooled to room temperature. The
solid was then filtered off and DMF was evaporated under
reduced pressure. The residue was triturated in ethyl acetate
(100 mL) and the solution was washed with water (20 mL),
brine (20 mL) and dried over MgSO4. After the solvent was
removed in vacuo, the residue was purified with column
chromatography (n-hexane/ethyl acetate, 10:1), to afford
compound 3a (1.62 g, 66%) as yellow liquid. 1H NMR
(CDCl3): d 10.48 (s, 1H), 7.59 (s, 1H), 7.34 (d, J¼8.7 Hz,
1H), 6.92 (d, J¼8.7 Hz, 1H), 5.03 (d, J¼7.8 Hz, 1H), 4.55–
4.52 (m, 1H), 4.13–4.03 (m, 4H), 3.10–3.02 (m, 2H), 2.0–
0.7 (m, 31H). IR (neat): 945, 1310, 1690, 1710, 1720,
4. Experimental
4.1. General
Melting points are uncorrected. 1H NMR spectra were
recorded on a Bruker AM-300 spectrometer with Me4Si as
internal standard. Mass spectra were record on a Finnigan
Mat-MD800 (EI), a Kratos Concept-1H (ESI) or Bruker
Daltonics FTMS-7 (MALDI-TOF) mass spectrometer.

3508
H. Chen et al. / Tetrahedron 59 (2003) 3505–3510
3250 cm21. EI-MS: m/z 478 [MþH]þ. Anal. calcd for
C27H43NO6: C, 67.90; H, 9.07; N, 2.93. Found: C, 67.95; H,
8.81; N, 2.82.
4H), 4.16–3.92 (m, 4H), 3.86 (t, J¼6.3 Hz, 4H), 3.40–3.15
(m, 4H), 2.00–0.20 (m, 84H), 22.76 (s, 2H). IR (KBr):
1691, 1705, 1730, 3315, 3400 cm21. ESI-MS: m/z 1614
[M]þ. Anal. calcd for C98H128N6O14: C, 72.92; H, 7.99; N,
5.21. Found: C, 72.66; H, 8.02; N, 4.98.
4.1.2. 2-tert-Butoxycarbonylamino-3-(3-formyl-4-meth-
oxy-phenyl)-propionic acid methyl ester 3b. A mixture
of 2 (1.40 g, 4.60 mmol), potassium carbonate (1.38 g,
10.0 mmol) and iodomethane (0.68 mL, 10.9 mmol) in
DMF (30 mL) was stirred at room temperature for 24 h.
The solid was then filtered off and the solvent evaporated
under reduced pressure. The residue was triturated in ethyl
acetate (100 mL) and the solution was washed with water
(20 mL), brine (20 mL) and dried over MgSO4. After the
solution was concentrated, the residue was purified with a
column chromatography (n-hexane/ethyl acetate, 3:1).
Compound 3b was obtained as yellow liquid (1.08 g,
4.1.5. Porphyrin 6b. Method A. Purple solid. Yield: 16%.
Mp 2908C. 1H NMR (CDCl3): d 8.90–8.75 (m, 4H), 8.69 (d,
J¼4.8 Hz, 4H), 8.40–8.25 (m, 4H), 8.10–8.00 (d,
J¼7.8 Hz, 4H), 7.75 (d, J¼2.1 Hz, 2H), 7.54–7.45 (d, d,
J¼4.5, 2.1 Hz, 2H), 7.27 (d, J¼4.5 Hz, 2H), 5.28 (d,
J¼5.9 Hz, 2H), 4.80–4.60 (m, 2H), 4.20–3.95 (m, 4H),
3.86 (t, J¼6.2 Hz, 4H), 3.40–3.10 (m, 4H), 2.00–0.20 (m,
62H), 22.76 (s, 2H). IR (KBr): 1690, 1742, 2220, 3140,
3452 cm21. ESI-MS: m/z 1409 [MþH]þ. Anal. calcd for
C86H102N8O10: C, 73.37; H, 7.30; N, 7.96. Found: C, 73.08;
H, 7.52; N, 7.73.
1
70%). H NMR (CDCl3): d 10.43 (s, 1H), 7.58 (s, 1H),
7.35 (d, J¼8.7 Hz, 1H), 6.97 (d, J¼8.7 Hz, 1H), 5.04 (d,
J¼5.5 Hz, 1H), 4.70–4.50 (m, 1H), 3.91 (s, 3H), 3.71 (s,
3H), 3.11–3.00 (m, 2H), 1.41 (s, 9H). IR (neat): 940, 1215,
1692, 1715, 1720, 3240 cm21. EI-MS: m/z 337 [M]þ. Anal.
calcd for C17H23NO6: C, 60.52; H, 6.87; N, 4.15. Found: C,
60.62; H, 6.90; N, 3.99.
4.1.6. Porphyrin 6c. Method A. Purple solid. Yield: 11%.
Mp 2878C. 1H NMR (CDCl3): d 8.95–8.83 (m, 4H), 8.73 (d,
J¼4.8 Hz, 4H), 8.65 (d, d, J¼4.3, 2.2 Hz, 4H), 8.41–8.36
(d, d, J¼4.3, 2.5 Hz, 4H), 7.78 (d, J¼1.5 Hz, 2H), 7.57–
7.52 (m, 2H), 7.27 (d, J¼9.0 Hz, 2H), 5.32 (d, J¼6.1 Hz,
2H), 4.80–4.70 (m, 2H), 4.20–3.95 (m, 4H), 3.89 (t,
J¼6.2 Hz, 4H), 3.40–3.15 (m, 4H), 1.70–0.20 (m, 62H),
22.73 (s, 2H). IR (KBr): 1345, 1432, 1535, 1680, 1740,
3146, 3460 cm21. MALDI-TOF-MS: m/z 1447 [M]þ. Anal.
calcd for C84H102N8O14: C, 69.69; H, 7.10; N, 7.74. Found:
C, 69.50; H, 7.28; N, 7.54.
4.1.3. 4-[Bis-(1H-pyrrol-2-yl)-methyl]-benzoic acid hexyl
ester 5b. A solution of compound 4b (0.56 g, 2.40 mmol)
and pyrrole (6.78 mL, 0.10 mol) was degassed by bubbling
with N2 for 10 min. Then trifluoroacetic acid (18 mL,
0.24 mmol) was added. The solution was stirred for 15 min
at room temperature, diluted with dichloromethane
(100 mL), then washed with 0.1 M aqueous sodium
hydroxide (20 mL), washed with water (10 mL), brine
(10 mL), and dried over Na2SO4. The solvent was removed
under reduced pressure and the residue was purified by
chromatography (chloroform as the eluent), to afford 5b as a
yellow liquid (0.61 g, 72%). 1H NMR (CDCl3): d 7.94–8.02
(m, 4H), 7.26 (d, J¼9.9 Hz, 2H), 6.71–6.70 (m, 2H), 6.16
(d, d, J¼3.0 Hz, J¼2.4 Hz, 2H), 5.95–5.80 (m, 2H), 5.52 (s,
1H), 4.29 (t, J¼6.4 Hz, 2H), 2.0–0.7 (m, 11H). IR (neat):
1715, 3240 cm21. EI-MS: m/z 350 [M]þ. Anal. calcd for
C22H26N2O2: C, 75.39; H, 7.48; N, 7.99. Found: C, 75.47;
H, 7.51; N, 8.20.
4.1.7. Porphyrin 6d. Method A. Purple solid. Yield: 6%.
Mp 2948C. 1H NMR (CDCl3): d 8.89–8.83 (m, 4H), 8.76 (d,
J¼4.2 Hz, 4H), 8.35 (d, J¼6.6 Hz, 4H), 8.07–8.02 (m, 4H),
7.79 (d, J¼1.8 Hz, 2H), 7.57–7.53 (d, d, J¼8.8, 2.0 Hz,
2H), 7.28 (d, J¼8.7 Hz, 2H), 5.34 (d, J¼7.5 Hz, 2H),
4.77–4.74 (m, 2H), 4.16–3.95 (m, 4H), 3.90 (t, J¼6.3 Hz,
4H), 3.36–3.27 (m, 4H), 1.70–0.20 (m, 62H), 22.73 (s,
2H). IR (KBr): 1215, 1678, 1736, 3156, 3458 cm21. ESI-
MS: m/z 1495 [MþH]þ. Anal. calcd for C86H102N6F6O10:
C, 69.15; H, 6.88; N, 5.63. Found: C, 69.47; H, 7.08; N,
5.35.
4.1.8. Porphyrin 7a and 8. Method B. A solution of
compound 3a (0.39 g, 0.81 mmol) and compound 5b
(0.28 g, 0.80 mmol) in chloroform (80 mL) was purged
with nitrogen for 15 min. Boron trifluoride etherate
(106 mL, 2.5 M stock solution in chloroform, 0.27 mmol)
was added. The solution was stirred for 1 h at room
temperature, and then DDQ (0.14 g, 0.61 mmol) was added.
The mixture was stirred for additional 1 h at room
temperature. The solvent was removed under reduced
pressure. After work-up, the residue was subjected to
column chromatography (n-hexane/dichloromethane, 1:10),
to give 7a (65 mg, 15%) and 8 (100 mg, 19%) as purple
solid. No expected tyrosine porphyrin product was purified.
4.1.4. Porphyrin 6a. Method A. A solution of compound 5b
(0.89 g, 2.54 mmol) and compound 3a (1.21 g, 2.54 mmol)
in acetonitrile (180 mL) was purged with nitrogen for
30 min. Then trifluoroacetic acid (50 mL, 0.65 mmol) was
added. The solution was stirred at room temperature for 5 h.
Then a solution of 2,3-dichloro-4,5-dicyanoquinone (DDQ)
(0.58 g, 2.55 mmol) in THF (20 mL) was added and the
mixture was stirred over night. The solvent was removed
and the residue was triturated with chloroform (150 mL).
The solution was washed with 1 M aqueous sodium
carbonate solution (30 mL), water (30 mL), brine (30 mL),
and dried over MgSO4. After the solvent was removed, the
residue was subjected to column chromatography (dichloro-
methane/diethyl ether, 200:1), to give 6a (124 mg, 6%) as a
purple solid. The product was further purified by recrys-
tallization from dichloromethane for microanalysis. Mp
2858C. 1H NMR (CDCl3): d 8.85–8.75 (m, 8H), 8.45–8.41
(d, d, J¼5.2, 3.9 Hz, 4H), 8.27 (d, J¼5.1 Hz, 4H), 7.76 (s,
2H), 7.53–7.49 (d, J¼3.8 Hz, 2H), 7.26–7.23 (m, 2H), 5.31
(d, J¼7.8 Hz, 2H), 4.74–4.70 (m, 2H), 4.51 (t, J¼6.6 Hz,
Compound 7a. Purple solid. Mp 2458C. 1H NMR (CDCl3): d
8.94–8.78 (m, 8H), 8.48–8.44 (m, 6H), 8.33–8.26 (m, 6H),
7.79 (d, J¼2.1 Hz, 1H), 7.55–7.50 (d, d, J¼7.5, 2.0 Hz,
1H), 7.30–7.22 (m, 1H), 5.35–5.27 (d, J¼6.0 Hz, 1H),
4.75–4.69 (m, 1H), 4.53 (t, J¼6.7 Hz, 6H), 4.13–3.97 (m,
2H), 3.90–3.85 (t, J¼6.3 Hz, 2H), 3.39–3.19 (m, 2H), 2.0–
0.25 (m, 64H), 22.76 (s, 2H). IR (KBr): 1678, 1724, 1743,

H. Chen et al. / Tetrahedron 59 (2003) 3505–3510
3509
3142, 3548 cm21. ESI-MS: m/z 1370 [MþH]þ. Anal. calcd
for C85H103N5O11: C, 74.48; H, 7.57; N, 5.11. Found: C,
74.79; H, 7.95; N, 4.76.
4.1.13. Porphyrin 10. A solution of compound 6e (0.12 g,
0.10 mmol) in a mixture of trifluoroacetic acid (5 mL) and
dichloromethane (5 mL) was stirred at room temperature for
4 h. Dichloromethane (50 mL) was added and the solution
was washed with water (3£15 mL), aqueous sodium
carbonate solution (1N, 10 mL), water (10 mL), brine
(10 mL), and dried with MgSO4. After the solvent was
removed under reduced pressure, the residue was purified
with column chromatography (dichloromethane/methanol,
50:1), to give porphyrin 10 (98 mg, 98%) as purple solid.
Compound 8. Purple solid. Mp 2888C. 1H NMR (CDCl3): d
8.84 (s, 8H), 8.46 (d, J¼7.8 Hz, 8H), 8.31 (d, J¼8.1 Hz,
8H), 4.52 (t, J¼6.9 Hz, 8H), 2.0–0.5 (m, 44H), 22.81 (s,
2H). IR (KBr): 1727, 3440 cm21. ESI-MS: m/z 1127 [M]þ.
Anal. calcd for C72H78N4O8: C, 76.70; H, 6.97; N, 4.97.
Found: C, 76.41; H, 7.17; N, 4.64.
1
Mp 236–2388C. H NMR (CDCl3): d 8.95–8.87 (m, 4H),
4.1.9. Porphyrin 6e. Method B. Purple solid. Yield: 32%.
Mp .3008C. 1H NMR (CDCl3): d 9.00–8.75 (m, 8H),
8.50–8.25 (m, 4H), 8.10–8.02 (d, d, 4H), 7.79 (d, 2H),
7.58–7.53 (d, d, 2H), 7.28 (d, 2H), 5.33 (d, J¼8.1 Hz, 2H),
4.77–4.74 (m, 2H), 3.70–3.50 (m, 12H), 3.36–3.20 (m,
4H), 1.40 (s, 18H), 22.73 (s, 2H). IR (KBr): 1217, 1324,
1670, 1735, 3150, 3450 cm21. ESI-MS: m/z [M]þ. Anal.
calcd for C66H62N6F6O10: C, 65.34; H, 5.15; N, 6.93.
Found: C, 65.17; H, 5.36; N, 6.78.
8.87–8.70 (m, 4H), 8.33 (d, 4H, J¼8.4 Hz), 8.04 (d, 4H,
J¼7.8 Hz), 7.78 (d, 2H, J¼1.5 Hz), 7.50 (d, J¼7.6 Hz, 2H),
7.25 (d, J¼7.4 Hz, 2H), 4.10–4.00 (m, 4H), 3.90 (t,
J¼5.4 Hz, 4H), 3.80–3.70 (br, 2H), 3.20–3.00 (m, 4H),
1.80–0.50 (m, 48H), 22.76 (s, 2H). IR (KBr): 1745,
3300 cm21. ESI-MS: m/z 1013 [MþH]þ. Anal. calcd for
C56H46F6N6O6: C, 66.40; H, 4.58; N, 8.30. Found: C, 64.06;
H, 4.98; N, 8.12.
4.1.14. Porphyrin 11. A mixture of compound 6e (0.10 g,
0.08 mmol) and lithium hydroxide monohydrate (28 mg,
0.67 mmol) in a mixture of tetrahydrofuran (20 mL) and
water (2 mL) was stirred for 1 h. Hydrochloric acid (1N)
was added to make pH¼6.5. The solvent was removed
under reduced pressure and the solid was washed with water
completely, dried, and then purified by column chromato-
graphy (dichloromethane/methanol, 50:1), to afford com-
pound 11 (85 mg, 86%) as purple solid. Mp 220–2228C. 1H
NMR (DMSO-d6): d 9.00–8.75 (m, 8H), 8.50–8.25 (m,
4H), 8.10–8.02 (d, d, J¼6.8 Hz, J¼3.2 Hz, 4H), 7.79 (d,
J¼2.0 Hz, 2H), 7.58–7.53 (d, d, J¼7.6, 1.9 Hz, 2H), 7.28
(d, J¼7.8 Hz, 2H), 5.33 (d, J¼8.1 Hz, 2H), 4.77–4.74
(m, 2H), 3.70–3.50 (m, 12H), 3.36–3.20 (m, 4H), 1.40 (s,
4.1.10. Porphyrins 7b. Method B. Purple solid. Yield: 18%.
Mp 2788C. 1H NMR (CDCl3): d 8.98–8.74 (m, 8H), 8.69–
8.64 (m, 6H), 8.42–8.37 (m, 6H), 7.80 (br, 1H), 7.55 (d,
J¼8.1 Hz, 1H), 7.27 (d, J¼8.4 Hz, 1H), 5.30 (d, J¼4.2 Hz,
1H), 4.76–4.71 (m, 1H), 4.13–3.98 (m, 2H), 3.89 (t,
J¼6.4 Hz, 2H), 3.40–3.18 (m, 2H), 1.60–0.20 (m, 31H),
22.77 (s, 2H). IR (KBr): 1345, 1534, 1670, 1726, 1745,
3135, 3460 cm21. ESI-MS: m/z 1120 [M]þ. Anal. calcd for
C64H64N8O11: C, 68.56; H, 5.75; N, 9.99. Found: C, 68.37;
H, 5.84; N, 9.68.
4.1.11. Porphyrins 7c. Method B. Purple solid. Yield: 30%.
Mp 2968C. 1H NMR (CDCl3): d 8.90–8.75 (m, 8H), 8.37–
8.30 (m, 6H), 8.07–8.03 (m, 6H), 7.79 (d, J¼6.4 Hz, 1H),
7.57–7.51 (m, 1H), 7.29–7.24 (m, 1H), 5.32–5.28 (d,
J¼4.0 Hz, 1H), 4.74–4.71 (m, 1H), 4.13–4.00 (m, 2H),
3.87 (t, J¼6.3 Hz, 2H), 3.34–3.21 (m, 2H), 1.60–0.20 (m,
31H), 22.77 (s, 2H). IR (KBr): 1067, 1324, 1745, 3160,
3456 cm21. ESI-MS: m/z 1191 [MþH]þ. Anal. calcd for
C67H64N5O5F9: C, 67.61; H, 5.42; N, 5.88. Found: C, 67.69;
H, 5.73; N, 5.32.
18H), 22.73 (s, 2H). IR (KBr): 1676, 1760, 3000 cm21
.
ESI-MS: m/z 1185 [M]þ. Anal. calcd for C64H58F6N6O10:
C, 64.86; H, 4.93; N, 7.09. Found: C, 64.56; H, 5.05; N,
6.95.
4.1.15. 2-Amino-3-(3-formyl-4-methoxy-phenyl)-pro-
pionic acid methyl ester 12. A solution of compound 3b
(50 mM) in trifluoroacetic acid was stirred at room
temperature for 2 h. The acid was removed under reduced
pressure and the residue was triturated with dichloro-
methane. After work-up, the crude product was purified by
flash chromatography (dichloromethane/methane 20:1), to
afford compound 12 as a white solid (95%). Mp 145–
1478C. 1H NMR (CDCl3): d 10.34 (s, 1H), 7.58 (s, 1H), 7.30
(d, J¼6. 8 Hz, 1H), 6.92 (d, J¼6.9 Hz, 1H), 3.90 (m, 1H),
3.79 (s, 3H), 3.68 (s, 3H), 3.10–3.02 (m, 2H). IR (KBr):
1710, 1745, 3200 cm21. EI-MS: m/z 237 [M]þ. Anal. calcd
for C12H15NO4: C, 60.75; H, 6.37; N, 5.90. Found: C, 60.52;
H, 6.58; N, 6.09.
4.1.12. Porphyrin 9. A solution of compound 3a (0.75 g,
1.58 mmol) and pyrrole (0.11 mL, 1.58 mmol) in chloro-
form (160 mL) was purged with nitrogen for 5 min. Boron
trifluoride etherate (0.21 mL, 2.5 M stock solution in
chloroform, 0.53 mmol) was added. The solution was
stirred for 1 h at room temperature. Then p-chloranil
(0.29 g, 0.12 mmol) was added and the mixture was
refluxing for 1 h. Triethylamine (73 mL, 0.53 mmol) was
added. The solvent was removed under reduced pressure.
After work-up as above for Method B, the residue was
subjected to chromatography (dichloromethane/ethyl
acetate, 25:1), to give compound 9 (50 mg, 6%) as a purple
1
solid. Mp 2658C. H NMR (CDCl3): d 8.73–8.69 (m, 8H),
7.78–7.71 (m, 4H), 7.52–7.47 (m, 4H), 7.25–7.20 (m, 4H),
5.27 (d, J¼8.1 Hz, 4H), 4.80–4.69 (m, 4H), 4.17–3.90 (m,
8H), 3.84–3.77 (m, 8H), 3.41–3.10 (m, 8H), 1.8–0.2 (m,
124H), 22.72 (s, 2H). IR (KBr): 1668, 1743, 3145,
3456 cm21. ESI-MS: m/z 2102 [MþH]þ. Anal. calcd for
C124H178N8O20: C, 70.89; H, 8.54; N, 5.33. Found: C,
70.44; H, 8.52; N, 4.76.
Acknowledgements
This work was financially supported by the National
Science Foundation of China (No. 90206005) and the
Ministry of Science and Technology (No. G2000078101) of
China. We thank Professors Ji-Liang Shi and Min Shi for
beneficial discussions.

3510
H. Chen et al. / Tetrahedron 59 (2003) 3505–3510
15. Jaln, R. K.; Hamilton, A. D. Org. Lett. 2000, 12, 1721.
References
16. Boitrel, B.; Baveux-Chambenoit, V.; Richard, P. Eur. J. Org.
Chem. 2001, 4213.
1. Ogoshi, H.; Mizutani, T. Acc. Chem. Res. 1998, 31, 81.
2. Purrello, R.; Gurrieri, S.; Lauceri, R. Coord. Chem. Rev. 1999,
190–192, 683.
17. Zhang, X.-X.; Lippard, S. J. J. Org. Chem. 2000, 65, 5298.
18. Jung, M. E.; Lazarova, T. I. J. Org. Chem. 1997, 62, 1553.
19. Zhang, X.-X.; Lippard, S. J. Inorg. Chem. 2000, 39, 4388.
20. Narayanan, S. J.; Sridevi, B.; Srinivasan, A.; Chandrashekar,
T. K.; Roy, R. Tetrahedron Lett. 1998, 39, 7389.
21. Shipps, G., Jr.; Rebek, J., Jr. Tetrahedron Lett. 1994, 35, 6823.
22. Littler, B. J.; Ciringh, Y.; Lindsey, J. S. J. Org. Chem. 1999,
64, 2864.
3. Ogoshi, H.; Mizutani, T. Curr. Opin. Chem. Biol. 1999, 3, 736.
4. Burrell, A. K.; Officer, D. L.; Plieger, P. G.; Reid, D. C. W.
Chem. Rev. 2001, 101, 2751.
5. Diederich, F. Chimia 2001, 55, 821.
6. Anderson, H. L.; Anderson, S.; Sanders, J. K. M. J. Chem. Soc.
Perkin Trans. 1 1995, 2231.
7. Reek, J. N. J.; Schenning, A. P. H. J.; Bosman, A. W.; Meijer,
E. W.; Crossley, M. J. Chem. Commun. 1998, 11.
8. Kuroda, Y.; Kawashima, A.; Hayashi, Y.; Ogoshi, H. J. Am.
Chem. Soc. 1997, 119, 4929.
23. Tietze, L. F.; Schulz, G. Chem. Eur. J. 1997, 3, 523.
24. Smith, K. M. In Porphyrins and Metalloporphyrins; Smith,
K. M., Ed.; Elsevier: Amsterdam, 1975; pp 29–58.
25. Boger, D. L.; Yohannes, D. J. Org. Chem. 1988, 53, 487.
26. Sudhoelter, E. J. R.; van Dijk, M.; Teunis, C. J.; Sanders,
G. M.; Harkema, S. J. Mater. Chem. 1996, 6, 357.
27. Littler, B. J.; Miller, M. A.; Hung, C.-H.; Wagner, R. W.;
O’Shea, D. F. J. Org. Chem. 1999, 64, 1391.
9. Ambroise, A.; Li, J.; Yu, L.; Lindsey, J. S. Org. Lett. 2000, 17,
2563.
10. Drain, C. M.; Russell, K. C.; Lehn, J.-M. Chem. Commun.
1996, 337.
11. Hunter, C. A.; Sarson, L. D. Angew. Chem. Int. Ed. Engl. 1994,
22, 2313.
28. Rao, P. D.; Dhanalekshmi, S.; Littler, B. J.; Lindsey, J. S.
J. Org. Chem. 2000, 65, 7323.
12. Kral, V.; Rusin, O.; Schmidtchen, F. P. Org. Lett. 2001, 6, 873.
13. Lai, T.-S.; Zhang, R.; Cheung, K.-K.; Che, C.-M.; Lai, T.-S.;
Kwong, H.-L. Chem. Commun. 1998, 1583.
14. Galardon, E.; Lukas, M.; Le Maux, P.; Simonneaux, G.
Tetrahedron Lett. 1999, 40, 2753.
29. Brueckner, C.; Karunaratne, V.; Rettig, S. J.; Dolphin, D. Can.
J. Chem. 1996, 74, 2182.
30. Dudic, M.; Lhotak, P.; Kral, V.; Lang, K.; Stibor, I.
Tetrahedron Lett. 1999, 40, 5949.