Sparsely substituted chlorins as core constructs in chlorophyll analogue chemistry. Part 1: Synthesis

Article abstract of DOI:10.1016/j.tet.2007.02.038

Five routes to stable chlorins bearing 0 or 1 meso substituents have been investigated, among which reaction of a 9-bromo-1-formyldipyrromethane and 2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin proved most effective. Application of this route afforded metal

Full text of DOI:10.1016/j.tet.2007.02.038

Tetrahedron 63 (2007) 3826–3839
Sparsely substituted chlorins as core constructs in chlorophyll
analogue chemistry. Part 1: Synthesis
Marcin Ptaszek, Brian E. McDowell, Masahiko Taniguchi,
*
Han-Je Kim and Jonathan S. Lindsey
Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA
Received 23 November 2006; revised 7 February 2007; accepted 9 February 2007
Available online 14 February 2007
Abstract—Five routes to stable chlorins bearing 0 or 1 meso substituents have been investigated, among which reaction of a 9-bromo-1-
formyldipyrromethane and 2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin proved most effective. Application of this route afforded metallo-
chlorins [Cu(II), Zn(II), and Pd(II)] including the chlorin lacking any b-pyrrole and meso substituents.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
chlorins for use in diverse applications also requires a funda-
mental understanding of how substituents alter reactivity. A
comprehensive treatment of the effects of substituents re-
quires access to chlorins bearing a systematic progression
of substituents, beginning with no substituents and proceed-
ing to one, two, or more groups at designated locations. An
ultimate objective of this work is to be able to design and
synthesize chlorins that exhibit desired spectral and photo-
physical properties for diverse applications ranging from
artificial photosynthesis to photomedicine.
The dihydroporphyrin, known as a chlorin constitutes the
chromophore of plant chlorophylls. In comparison with
porphyrins, chlorins absorb more strongly in the red region
of the spectrum.1 The prototypical chlorins are chlorophyll
a and chlorophyll b, whose structure and absorption spectra
are shown in Figure 1. The spectra differ owing to the
presence of the methyl group or the formyl group at the 7-
position. Thus, chlorin spectra can be significantly altered
upon modification of even a single substituent. To gain
a deep understanding of the effects of substituents on the
spectral properties of chlorins requires the ability to prepare
chlorins bearing diverse patterns of substituents. To tailor
Surprisingly few systematic studies are available concerning
the effects of substituents on chlorin properties. The dearth
stems largely from synthetic limitations. Two simple routes
Figure 1. Absorption spectra of chlorophyll a (solid line) and chlorophyll b (dashed line) in diethyl ether at room temperature.2 The chlorin numbering system is
shown at right.
Keywords: Chlorin; Hydroporphyrin; Hydrodipyrrin; Dipyrromethane.
* Corresponding author. Tel.: +1 919 5156406; fax: +1 919 5132830; e-mail: jlindsey@ncsu.edu
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.038

M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
3827
to chlorins entail (1) derivatization of naturally occurring
chlorins,3 and (2) reduction/derivatization of synthetic por-
phyrins.4 The former route is constrained by the numerous
substituents present in the naturally occurring macrocycles.
The lack of regioselectivity of the latter route typically limits
the scope to the reduction of porphyrins having substitution
patterns (giving 4-fold or 2-fold symmetry) wherein regio-
isomers cannot form. Benchmark chlorins of the latter type
include meso-tetraphenylchlorin (H2TPC)5 and octaethyl-
chlorin (H2OEC),6 which are commercially available, and
5,15-diphenylchlorin.7 Analogues such as meso-tetrakis(3-
hydroxyphenyl)chlorin,8 2,3-dihydroxy-meso-tetraphenyl-
chlorin,9 and diverse 5,15-diarylchlorins10 have been
prepared for studies of photodynamic therapy.
affords the corresponding ZnChlorin73 but no preparative
procedure has been reported. Regardless, all of the hydro-
porphyrins shown in Chart 1 are susceptible to adventitious
dehydrogenation to give the porphyrin in an aerobic environ-
ment, and thus have limited stability toward routine handling
in the laboratory.
The naturally occurring chlorins bonellin (a non-photosyn-
thetic pigment) and Faktor I (a biosynthetic intermediate)
each contain a geminal dialkyl group in the pyrroline ring,
which stabilizes the chlorin to dehydrogenation (Chart 2).
Total syntheses of these ‘C-methylated chlorins’ and other
naturally occurring chlorins have been developed; however,
such syntheses are necessarily elaborate owing to the chal-
lenges of installing the multiple b-pyrrolic and pyrrolinic
substituents.74
The chlorin lacking any substituents, 2,3-dihydroporphine
(known as ‘chlorin’ itself, is termed here as H2Chlorin;
Chart 1), has been the subject of theoretical calculations11
and numerous spectroscopic studies.12–69 The latter include
fundamental studies to probe chlorin features, as well as
spectral hole-burning experiments to probe the utility of
chlorins in optical information storage applications. How-
ever, such a potentially valuable benchmark has not been
employed for studies of reactivity (other than dehydrogena-
tion70), presumably owing to the limited quantities of avail-
able material. The only reported synthesis of H2Chlorin
entails Grignard-mediated cyclization of 2-(N,N-dimethyl-
aminomethyl)pyrrole.71,72 Photoreduction of zinc porphine
The methodology developed for preparing bonellin and
Faktor I has been extended to gain access to synthetic chlor-
ins bearing more simple substituent patterns (while retain-
ing the geminal dimethyl group).75–78 Two routes that we
developed in this regard include (I) reaction of a 9-bromo-
dipyrromethane-1-carbinol (Eastern half) and a 1,3,3-tri-
methyltetrahydrodipyrrin (Western half),76 and (II) reaction
of a 9-bromodipyrromethane-1-carboxaldehyde (Eastern
half) and the same 1,3,3-trimethyltetrahydrodipyrrin (West-
ern half). The two routes are shown in Scheme 1. The West-
ern half incorporates a geminal dimethyl group that ensures
Chart 1.
Chart 2.
Scheme 1.

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M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
the presence of the reduced, pyrroline ring in the resulting
chlorin, thereby precluding adventitious dehydrogenation
leading to the porphyrin. In each case, the reaction proceeds
in a two-step process of condensation of the Eastern and
Western halves to give a 1-methyl-19-bromo-bilane deriva-
tive, and metal-mediated oxidative cyclization of the latter
to give the corresponding chlorin.
and increase the scope, and a new route that entails reaction
of a 9-formyltetrahydrodipyrrin and a dipyrromethane. The
synthetic routes described herein have enabled examination
of the fundamental reactivity, structure, and spectral proper-
ties of stable chlorins bearing few or no substituents, as are
described in the companion papers.81,82
The two routes are similar in a number of respects but
also differ in the conditions for condensation, nature of the
acyclic intermediate, and substituent patterns in the resulting
chlorins. Route I has provided access to chlorins bearing two
substituents (5,10-,75,76 5,12-,79 and 5,8-79) or three substit-
uents (2,5,12-,79 5,10,15-,80 and 5,10,20-80) at sites other
than the pyrroline ring, and each chlorin has contained a
5-substituent (see Fig. 1 for chlorin numbering system). Rea-
sonable yields of chlorin macrocycle formation (12%–45%)
have facilitated preparation of 5,10-disubstituted chlorins in
>100-mg quantities, as required for a variety of applica-
tions. Route II, developed very recently and described
herein, has been applied to access zinc chlorins bearing
two substituents (3,13-), three substituents (3,10,13-), and
no meso- or b-pyrrole substituents.77 By contrast with route
I where each chlorin contains a 5-substituent, the develop-
ment of route II for the synthesis of sparsely substituted,
5-unsubstituted chlorins has presented a number of unex-
pected challenges.
2. Results and discussion
The shorthand nomenclature for the chlorins described
herein employs the following abbreviations with super-
scripts to denote substituents and their positions: B (3,5-di-
tert-butylphenyl), P (phenyl), M (mesityl), and T (p-tolyl).
2.1. Synthesis of chlorins bearing one substituent
(5-position)
The synthesis of a chlorin bearing a lone substituent located
at the 5-position was carried out following route I76 (Scheme
1). Thus, acylation83 of dipyrromethane (1a)84 using benzo-
thioate 2-B76 or 2-T85 gave the 1-acyldipyrromethane 3-B or
3-T in 71% or 39% yield, respectively (Scheme 2). Treat-
ment of 3-B with NBS afforded 4-B in 53% yield. Reduction
of 4-B with NaBH4 gave the corresponding carbinol 4-B-
OH (Eastern half), which upon condensation with 2,3,4,5-
tetrahydro-1,3,3-trimethyldipyrrin (5, Western half)76 using
TFA gave the tetrahydrobilene-a (6-B) in 53% yield. Treat-
ment of the latter to metal-mediated oxidative cyclization
conditions [AgOTf, 2,2,6,6-tetramethylpiperidine (TMPi)
and Zn(OAc)2 in refluxing CH3CN exposed to air] afforded
chlorin ZnC-B5 in 17% yield. The same approach was used
with 1-acyldipyrromethane 3-T but the limited stability of
the corresponding 9-bromo species 4-T prompted in situ
conversion to the chlorin. Thus, bromination of 3-T and
subsequent condensation with 5 yielded putative tetrahydro-
bilene-a 6-T, which was converted to chlorin ZnC-T5 in 7%
overall yield (from 3-T).
In this paper, we describe the investigation of the synthesis
of sterically uncongested, stable chlorins possessing no b-
pyrrole substituents and no or only one meso substituent
(at the 5- or 10-position). A 5-substituted chlorin was pre-
pared via route I. Five routes were investigated to prepare
5-unsubstituted chlorins. The investigation entailed use of
two types of Western halves and five types of Eastern halves.
The routes found suitable for preparing 5-unsubstituted
chlorins include route II (described above), two modified
versions of route II designed to facilitate implementation
Scheme 2.

M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
3829
2.2. Synthesis of chlorins lacking a 5-substituent
treated to the conditions for metal-mediated oxidative cycliza-
tion, the differing oxidation states of A, B, and C are expected
to give rise to different properties and ease of oxidation.
(1) Retrosynthetic analysis. We investigated five routes
(I–V) to the target chlorin bearing no substituents (R¼H)
or one substituent at the 10-position (R¼aryl), as shown in
Scheme 3. The routes are based on the ready availability
of dipyrromethanes (1) and the tetrahydrodipyrrin 5. The
2+2 synthesis of a chlorin entails condensation of an Eastern
half (composed of two pyrrole units) and a Western half
(composed of one pyrrole and one pyrroline unit). The two
halves must have complementary sets of reactive nucleo-
philic and electrophilic positions. The routes differ from
each other in the placement of reactive groups on the two
halves: the a-pyrrolic position and the pyrrolinic methyl
group react as nucleophiles, whereas the a-bromo-, formyl,
and hydroxymethylpyrrolic groups serve as electrophiles.
A key issue in the condensation concerns the lability of the
Eastern half and Western half under the reaction conditions
employed, particularly the level of acid present in the con-
densation. A requirement for stronger acidic conditions
is expected for the condensation in each of routes I–V
(pyrrolic-carboxaldehyde or 1ꢀ pyrrole-carbinol) to give a
5-unsubstituted chlorin versus that employed to give a
5-substituted chlorin (2ꢀ pyrrole-carbinol in route I). How-
ever, strong acid causes the Western half 5 to undergo irre-
versible rearrangement to a bicyclic product,76 and Eastern
halves can undergo cleavage. The liberation of free pyrrolic
species upon acidolysis of an Eastern half opens the door to
the formation of chlorin byproducts as well as porphyrin spe-
cies. Dipyrromethanes bearing meso-aryl substituents are
more prone to acidolysis than those lacking a meso substit-
uent.86 Even in the absence of acid, bromo-dipyrromethanes
(e.g., many of the Eastern halves) are inherently reactive.
Thus, conditions to force the reaction of Eastern and Western
halves, such as strong acid or elevated temperature, are of
limited utility.
The routes also differ in the nature of the intermediates ex-
pected upon condensation of the Eastern half and Western
half. The intermediates are shown in the retrosynthetic
scheme. Intermediate A is a 2,3,4,5-tetrahydrobilene-a, B
is a 2,3,4,5-tetrahydrobiladiene-ab, and C is a 2,3,4,5-tetra-
hydrobilatriene-abc. While the intermediates obtained upon
condensation are typically not characterized but instead are
Scheme 3. Routes to 5-unsubstituted chlorines.

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M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
(2) Route I. Access to a 5-unsubstituted chlorin via route I
(Scheme 1) requires use of a 1ꢀ carbinol rather than a 2ꢀ car-
binol. The synthesis of such chlorins required preparation of
1-formyldipyrromethanes. Thus, Grignard-mediated formyl-
ation (with phenyl formate) of dipyrromethane (1a), 5-phe-
nyldipyrromethane (1b), and 5-mesityldipyrromethane (1c)
gave the corresponding 1-formyldipyrromethanes 7a–c.87
Treatment of 7c with NBS gave the 1-bromo-9-formyldipyr-
romethane 8c in 67% yield. Reduction of 8c with NaBH4
afforded the 1-bromo-9-hydroxymethyldipyrromethane
8c-OH. Reaction of 8c-OH with 5 under the standard
conditions75 of TFA catalysis followed by metal-mediated
oxidative cyclization afforded the corresponding chlorin
ZnC-M10 in <1% yield (Scheme 4). We attributed the low
yield to the poor reactivity of the 1ꢀ carbinol. Related studies
of the reaction of similar dipyrromethane-carbinols in por-
phyrin-forming conditions have also given quite low yields.88
Scheme 4. Route I.
(3) Route II. (a) Standard procedure. Route II utilizes a
1-bromo-9-formyldipyrromethane (Eastern half) and the
tetrahydrodipyrrin (Western half). Treatment of a 1-formyl-
dipyrromethane (7a–c) with NBS gave the corresponding
9-bromo-1-formyldipyrromethane 8a–c in 55%–78%
yields. The condensation of 9-bromo-1-formyldipyrro-
methane (8a) and Western half 5 was carried out with
1 equiv of BF3$O(Et)2 in CH3CN, which gave no reaction
after 15 min, while excess BF3$O(Et)2 resulted in decom-
position of 5. Battersby reported the condensation of a
1-formyldipyrromethane and a tetrahydrodipyrrin using
p-toluenesulfonic acid (p-TsOH$H2O) in MeOH, affording
an intermediate 2,3,4,5-tetrahydrobiladiene-ab on the path
to a copper chlorin.89 Note that the Eastern half and Western
half reactants employed by Battersby contained several
b-substituents and no meso substituents. We performed
the condensation of 8a and 5 using 13.5 mM reactants and
5 mol equiv (68 mM) of p-TsOH$H2O in methanol (Scheme
5). The putative protonated 2,3,4,5-tetrahydrobiladiene-ab
was observed with a maximum absorption centered at
480 nm (to be compared with Battersby’s tetrahydro-
biladiene-ab at 496 nm89), an absorption characteristic of
dipyrrin chromophores.
Scheme 5. Route II.
The crude mixture was then subjected to the standard condi-
tions76 for metal-mediated oxidative cyclization, affording
the desired zinc chlorin ZnC in 9% yield. The similar reac-
tion of 9-bromo-1-formyldipyrromethane 8b or 8c afforded
ZnC-P10 or ZnC-M10 in 10% or 12% yield, respectively. A
microscale study of the concentration dependence of the
condensation of 8a and 5 (and 5 mol equiv of p-TsOH$H2O
in CH2Cl2/MeOH) identified improved yields upon doubling
the concentration of the condensation reactants. Thus, reac-
tion using 26 mM Eastern and Western halves afforded
workable quantities (66–104 mg) of ZnC, ZnC-P10 or
ZnC-M10 in 16%, 33% or 42% yield, respectively. The syn-
theses of ZnC and ZnC-M10 in this manner were reported in
a separate publication.77
(3b) Streamlined route II. The clean bromination of 1-for-
myldipyrromethane 7a suggested a streamlined three-step

M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
3831
Table 1. Exploration of the metal-mediated oxidative cyclization of a tetra-
hydrobiladiene-aba
procedure for chlorin synthesis. Thus, 7a was brominated
with NBS and the crude reaction mixture was carried
through the two-step procedure for chlorin formation as de-
scribed above. The yield of chlorin ZnC in the three-step
procedure was 18% (145 mg) versus w12% (104 mg)77 in
the standard procedure (Scheme 5). The streamlined three-
step procedure is advantageous in avoiding chromatography
following step one, and employing a simple workup in
step two.
Entry Metal salt
Baseb
Solvent Product
Yield (%)
9c
1
2
3
4
5
6
Zn(OAc)2
Zn(OAc)2
Zn(OAc)2
Pd(OAc)2
Pd(OAc)2
TMPi
DBU
DIEA MeCN
TMPi MeCN
KOHe EtOH
MeCN
MeCN
ZnC-P10 37c
ZnC-P10
ZnC-P10 10c
PdC-P10
PdC-P10
PdC-P10
CuC-P10
12d
6d
Pd(MeCN)2Cl2 KOHe EtOH
6d
7
8
9
Cu(OAc)2
Cu(OAc)2
SnCl2
TMPi
MeCN
4d
KOHe EtOH
CuC-P10 14d
SnC-P10
—
—
5c
0
0
0
0
0
0
0
(3c) AgOTf-free route II. In several cases we attempted to
isolate the tetrahydrobiladiene-ab intermediate. In the
reaction of 8a+5, the resulting unsubstituted tetrahydro-
biladiene-ab (9a-Br) was not isolated due to decomposition
upon flash chromatography. However, the phenyl-
substituted tetrahydrobiladiene-ab (9b-Br, derived from
8b+5) was more stable and was readily isolated by flash
TMPi
TMPi
TMPi
TMPi
TMPi
TMPi
DBU
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
10
11
12
13
14
15
16
MgBr2
Co(OAc)2
NiCl2
CdCl2
No metal
No metal
No metal
—
—
—
—
DIEA MeCN
—
1
a
chromatography (silica and CH2Cl2). The H NMR spec-
The crude biladiene 9b-Br was prepared by p-TsOH-catalyzed condensa-
tion of 5 and 8b under standard conditions. The reaction mixture was then
neutralized by the base to be used in the metal-mediated oxidative cycli-
zation (when KOH was used as a base in metal-mediated cyclization,
crude 9b-Br was neutralized by triethylamine). Unless noted otherwise
each reaction was performed at 10 mM concentration with 15 equiv of
metal salt and 30 equiv of base.
Bases include 2,2,6,6-tetramethylpiperidine (TMPi), 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU), and N,N-diisopropylethylamine (DIEA).
Spectroscopic yield (from 8b) unless noted otherwise, assuming a fixed
molar absorption coefficient in all cases (see Section 4).
Isolated yield.
trum revealed a mixture of diastereomers, which made indi-
vidual proton assignments difficult. However, two pyrrole
NH protons were clearly observed at 7.83 and 8.18 ppm,
consistent with a tetrahydrobiladiene structure.
b
c
We then turned to investigate alternative conditions for the
metal-mediated, oxidative cyclization of the tetrahydro-
biladiene-ab. The traditional method employs Zn(OAc)2,
AgOTf, and 2,2,6,6-tetramethylpiperidine in refluxing
acetonitrile exposed to air. Prior omission/reconstitution
experiments concerning route I revealed that omission of
Zn(OAc)2 and 2,2,6,6-tetramethylpiperidine resulted in
failure to form any detectable chlorin, whereas omission of
AgOTf gave chlorin albeit in diminished yield.76 Here we
explored the cyclization in the presence of various metal
salts and bases in refluxing solvents exposed to air but with-
out any AgOTf (i.e., a AgOTf-free step 3 in route II). In each
case, the p-TsOH-catalyzed condensation of 5 and 8b gave
the crude reaction mixture containing 9b-Br. The latter
was neutralized with an appropriate base, dissolved in a
given solvent, and treated with a base and metal salt (Scheme
6). The resulting reaction mixture was refluxed until the
absorption spectrum remained relatively unchanged. The
results are summarized in Table 1.
d
e
Five equivalents were employed.
metallochlorin. Each metal reagent examined gave an
absorption spectrum consistent with the metal complex of
9b-Br, regardless of whether the chlorin ultimately was
obtained. The metal reagents that successfully gave chlorin
include Zn(II) (entries 1–3), Pd(II) (entries 4–6), Cu(II)
(entries 7 and 8), and Sn(II) (entry 9) but not Mg(II),
Co(II), Ni(II), Cd(II) or no metal (entries 10–16) under the
conditions examined. The best yield typically was observed
when 2,2,6,6-tetramethylpiperidine was used in acetonitrile.
In the case of Cu(II), a better yield was observed for
KOH/EtOH, conditions (entry 8) developed previously for
the synthesis of palladium porphyrins.90 The procedure of
acid-catalyzed condensation followed by AgOTf-free
metal-mediated oxidation was applied to give milli-
gram quantities of CuC, PdC, CuC-P10, ZnC-P10, and
PdC-P10.
A few indium(III) reagents were examined in place of zinc
acetate in the AgOTf-free chlorin-forming reaction [InCl3,
InBr3, and In(OAc)3] to prepare X-InC-P10 where X is
the counteranion. Each indium reagent afforded the corre-
sponding indium(III)chlorin inw30% yield (observed spec-
troscopically), with the cleanest reaction observed for
In(OAc)3. Contrary to other chlorin chelates examined
herein, the indium(III)chlorin was highly polar and proved
difficult to purify by chromatography. Moreover, we ob-
served partial conversion of the indium(III)chlorin on silica
(ethyl acetate) into another less polar chlorin. In the case of
reaction with InCl3, the two indium(III)chlorin species were
separated (although not isolated in pure form), and exhibited
spectroscopic properties (LDMS, UV–vis, only slightly
Scheme 6. AgOTf-free step 3 of route II.
1
With a number of metal salts, the (AgOTf-free) metal-medi-
ated oxidative cyclization of 9b-Br gave the corresponding
different H NMR spectra) that were similar to each other.
In the case of reaction with In(OAc)3, chromatography

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M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
[alumina, ethyl acetate/ethyl acetate/MeOH (10:1)]
followed by preparative SEC (THF) afforded the expected
indium(III)chlorin in nearly pure form as determined by
1
TLC and H NMR spectroscopy. However, attempts at fur-
ther purification on alumina [ethyl acetate/MeOH (10:1)]
caused formation of a second indium(III)chlorin in almost
equal amount. The two chlorins were observed by TLC
1
and H NMR spectroscopy but could not be separated. In
this regard, it is noteworthy that Pandey’s group observed
the formation of two indium-chelated species upon metala-
tion of a free base chlorin related to methyl pyropheophor-
bide.91 Thus, an indium-chlorin of unambiguous identity
was not obtained.
Scheme 7. Route III.
(5) Route IV. Route IVemploys the 9-formyltetrahydrodipyr-
rin (Western half) and a 1-bromodipyrromethane (Eastern
half). 9-Formyltetrahydrodipyrrin 11 was obtained by stan-
dard Vilsmeier formylation of 5.96 The reaction of 1c with
NBS in THF at ꢁ78 ꢀC afforded a mixture of the 1-bromo-
dipyrromethane and 1,9-dibromodipyrromethane together
with unreacted starting material. Column chromatography
of the crude mixture afforded the known 1-bromodipyrro-
methane 12c75 in 35% yield. 1-Bromodipyrromethanes
such as 12c (as well as 12a and 12b, derived from 1a and
1b) are prone to decomposition during purification and
routine handling.
Attempts to form chlorin directly from 8b and 5 by refluxing
a mixture of both halves in EtOH in the presence of KOH and
an appropriate metal salt (thereby avoiding p-TsOH-cata-
lyzed condensation) resulted in a mixture of chlorin and
porphyrin products (the latter formed by self-condensation
of the Eastern half), or no macrocycle formation. We previ-
ously employed imine derivatives of 1,9-formyldipyrro-
methanes for condensation with zinc acetate (and no other
acid) to give the trans-AB-porphyrin.92 Condensation using
the N-propyliminomethyl analogue of 8b (PrN-8b) and
Western half 5 (100 mM each) in ethanol afforded chlorin
ZnC-P10, albeit in only 3.3% yield. Thus, the synthesis of
chlorins requires the acid-catalyzed condensation of Eastern
and Western halves.
The condensation of 11 and 1-bromodipyrromethane 12c
was carried out in CH2Cl2 in the presence of 5 equiv of
p-TsOH$H2O. Absorption spectroscopy of the crude reac-
tion mixture showed a strong band at l¼478 nm, attributed
to the protonated tetrahydrobiladiene. After quenching with
NaHCO3, the crude biladiene was subjected to metal-
mediated oxidative cyclization under standard conditions,
affording the chlorin ZnC-M10 in w8% yield (Scheme 8).
Attempts to use 1-cyano-5-phenyldipyrromethane87 or
1-carboethoxy-5-phenyldipyrromethane87 in place of 12c
did not give chlorin. The statistical bromination of the di-
pyrromethane and the apparent instability of the resulting
1-bromodipyrromethane limited the utility of this route.
Accordingly, no further studies of this route were performed.
In summary, following the acid-catalyzed condensation, var-
ious metallochlorins [Cu(II), Zn(II), Pd(II), and putative
In(III)] can be prepared via a AgOTf-free metal-mediated
oxidative cyclization process. The indium chelate proved
difficult to purify to homogeneity. Tetrapyrrolic complexes
of Pd(II) and In(III) are potentially useful in the life sciences
for photodynamic therapy, and In(III) chelates may be used
for photosensitization, imaging, and/or radiotherapy ap-
plications. Although palladium and indium chelates of
porphyrins are well known, there are only a few reports
about Pd(II)93 and In(III)91,94 complexes of chlorins, hence
this straightforward route to metallochlorins warrants
further investigation.
(4) Route III. Route III employs the same Western half as in
routes I and II but uses a 1-bromo-9-formyldipyrrin as an
Eastern half rather than a 1-bromo-9-formyldipyrromethane.
This route was considered to be attractive owing to the
greater stability of dipyrrins versus dipyrromethanes. The
condensation should afford a 2,3,4,5-tetrahydrobilatriene
intermediate, which is more oxidized than the 2,3,4,5-tetra-
hydrobiladiene formed in route II, and thereby require a
lesser quantity of oxidant to yield the chlorin.
Dipyrromethane 8b was treated with DDQ at room tem-
perature in CHCl3,95 affording 1-bromo-9-formyldipyrrin
10b in 50% yield (Scheme 7). Dipyrrin 10b was subjected
to p-TsOH-catalyzed condensation followed by metal-
mediated oxidative cyclization. Absorption spectroscopy of
the crude reaction mixture showed only a small amount of
chlorin (<1%). The origin of the low yield appears to
stem from the low reactivity of the formyl group in the
dipyrrin moiety, because 10b remained unreacted follow-
ing attempted acid-catalyzed condensation.
Scheme 8. Route IV.
(6) Route V. Route V avoids any functionalization of the
starting dipyrromethane (Eastern half) by condensation of

M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
3833
the dipyrromethane with a 9-formyltetrahydrodipyrrin
(Western half). Subsequent 19-bromination of the resulting
biladiene sets the stage for standard metal-mediated oxida-
tive cyclization.
(7) Comparison of routes. Of the routes investigated, route
II and its variants appear most useful. Indeed, the stream-
lined route II was employed to prepare 145 mg of the bench-
mark chlorin ZnC lacking any meso- or b-pyrrole
substituent. In addition, the AgOTf-free version of route II
provides direct access to metallochlorins containing Cu(II),
Zn(II), and Pd(II).
Treatment of a mixture of 11 and 1a with 5 equiv of
p-TsOH$H2O in CH2Cl2/MeOH afforded the corresponding
tetrahydrobiladiene 9b (Scheme 9). (The tetrahydrobila-
diene was formed in 21% yield if the peak molar absorption
coefficient is 100,000 Mꢁ1 cmꢁ1.) Treatment of crude 9b
with NBS in THF at ꢁ78 ꢀC afforded the putative 19-bromo-
tetrahydrobiladiene 9b-Br. The bromination proved difficult
to verify: LDMS did not show a peak corresponding to the
expected 9b-Br, and absorption spectroscopy did not show
any changes compared with that of 9b. Regardless, the crude
reaction mixture after bromination was subjected to metal-
mediated oxidative cyclization for 24 h, affording chlorin
3. Outlook
Three distinct methods of chlorin synthesis include modi-
fication of naturally occurring chlorins, reduction/derivati-
zation of porphyrins, and de novo synthesis. Of these,
de novo synthesis affords the most versatility. The reaction
of 1-formyl-9-bromo-dipyrromethane and 2,3,4,5-tetra-
hydro-1,3,3-trimethyldipyrrin affords the corresponding
chlorin bearing only a geminal dimethyl group at the 18-
position. The reaction can be carried out with several
variations: (i) in a three-step process (9-bromination of the
1-formyldipyrromethane, acid-catalyzed condensation to
form the tetrahydrobiladiene-ab, and metal-mediated oxi-
dative cyclization), (ii) in a streamlined manner where the
1-formyl-9-bromo-dipyrromethane is used in crude form,
and/or (iii) with a AgOTf-free metal-mediated oxidative
cyclization process. The AgOTf-free route provides direct
access to a selection of metallochlorins. Similar reaction
enables synthesis of a chlorin bearing one additional substit-
uent at the 10-position. In conjunction with other synthetic
methods, simple routes are now available for preparing
stable chlorins that bear no substituents, a single substituent
at the 5- or 10-position, or two or three distinct meso substit-
uents. All of the synthetic chlorins prepared herein were
stable upon routine handling in aerobic environments, in-
cluding use of procedures such as chromatography, recrys-
tallization, and standing in solution on the open benchtop.
The ready synthesis and stability of the chlorins enabled
the studies of derivatization chemistry and spectroscopic
properties described in the companion papers.81,82
1
in w8% yield. The H NMR and LDMS analyses revealed
the presence of various monobromochlorins in the purified
sample. Separation of those species proved difficult, which
makes this route completely unattractive.
4. Experimental section
4.1. General methods
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were
collected at room temperature in CDCl3 unless noted other-
wise. NMR spectroscopy was not performed on Cu(II)
chelates of the chlorins. Chlorins were analyzed by laser de-
sorption mass spectrometry without a matrix (LDMS).76,97
Fast atom bombardment mass spectrometry (FABMS) data
are reported for the molecule ion or protonated molecule
ion. Melting points are uncorrected. NBS was recrystallized
(H2O). Chromatography was performed with flash silica
(80–200 mesh). Absorption and fluorescence spectra were
obtained in toluene at room temperature.
4.2. Solvents
THF was distilled over sodium metal and benzophenone
as required. Methanol, CH3CN, and CH2Cl2 were used as
anhydrous grade. Toluene used in absorption and fluores-
cence studies was spectroscopic grade. All other solvents
were used as received.
Scheme 9. Route V.

3834
M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
4.3. Noncommercial compounds
without heating. Column chromatography [silica packed and
eluted with hexanes/CH2Cl2 (1:1), then eluted with hexanes/
ethyl acetate (7:1)] afforded a light brown powder (493 mg,
Compounds 1a,84 2-B,76 2-T,85 5,76,98 7a–c,87 and 1196 were
prepared as described in the literature. Compound 12c was
prepared as described in the Supporting Information of
Ref. 75.
1
53%): mp 120 ꢀC (dec); H NMR d 1.31 (s, 18H), 4.08 (s,
2H), 5.92–5.94 (m, 1H), 5.95–5.97 (m, 1H), 6.18–6.20 (m,
1H), 6.86–6.88 (m, 1H), 7.61–7.64 (m, 1H), 7.70–7.73 (m,
2H), 9.66–9.76 (br, 1H), 11.37–11.46 (br, 1H); 13C NMR
(dec in CDCl3); FABMS obsd 441.1541, calcd 441.1541
[(M+H)+, M¼C24H29BrN2O].
4.3.1. Synthesis of 5-substituted chlorins.
4.3.1.1. 1-(3,5-Di-tert-butylbenzoyl)dipyrromethane
(3-B). Following a general procedure,83 EtMgBr (16.4 mL,
16 mmol, 1.0 M in THF) was added to a solution of dipyrro-
methane 1a (1.00 g, 6.48 mmol) in dry THF (10 mL) at room
temperature under argon. The mixture was stirred at room
temperature for 10 min and then cooled to ꢁ78 ꢀC. A solu-
tion of S-2-pyridyl 3,5-di-tert-butylbenzothioate (2-B)
(2.24 g, 6.84 mmol) in dry THF (10 mL) was added. The
reaction mixture was maintained at ꢁ78 ꢀC for 30 min,
whereupon the cooling bath was removed. After 1 h, the re-
action was quenched by addition of 100 mL of saturated
aqueous NH4Cl. The reaction mixture was extracted with
CH2Cl2. The organic extract was washed with water, dried
(Na2SO4), and concentrated under reduced pressure.
Column chromatography [silica; packed and eluted with
hexanes/CH2Cl2 (1:2), then eluted with hexanes/ethyl ace-
tate (5:1)] afforded a white powder (1.76 g, 71%): mp
4.3.1.4.
19-Bromo-10-(3,5-di-tert-butylphenyl)-
2,3,4,5-tetrahydro-1,3,3-trimethylbilene-a (6-B). Follow-
ing the procedure for preparing a tetrahydrobilene-a,76
a sample of 4-B (441 mg, 1.00 mmol) was reduced with
NaBH4 (378 mg, 10.0 mmol) in anhydrous THF/methanol
(20 mL, 4:1). The resulting solid was dissolved in 10 mL
of anhydrous CH3CN, to which 5 (190 mg, 1.00 mmol)
and TFA (77 mL, 1.0 mmol) were added. The reaction mix-
ture was stirred at room temperature for 30 min. Then 10%
aqueous NaHCO3 (50 mL) was added, and the mixture
was extracted with distilled CH2Cl2. The organic extract
was washed with water, dried (NaHCO3), and concentrated
in vacuo without heating. The resulting brown solid was
purified by chromatography [silica and hexanes/ethyl ace-
tate (5:1)/ethyl acetate] to give a brown solid (325 mg,
53%; mixture of stereoisomers): mp 107–110 ꢀC; 1H NMR
d 0.91 (s, 3H), 1.06 (s, 3H), 1.26 (s, 18H), 1.86–1.90 (m,
3H), 2.18–2.34 (m, 2H), 2.56 (ABX, 3J¼10.8 Hz,
2J¼14.8 Hz, 1H), 2.71 (ABX, 3J¼3.2 Hz, 2J¼14.8 Hz,
1H), 3.60–3.64 (m, 1H), 3.85 (s, 2H), 5.27–5.31 (m, 1H),
5.70–5.99 (m, 6H), 7.05 (s, 2H), 7.26 (s, 1H), 7.81–7.90
(m, 1H), 8.21–8.39 (m, 1H), 8.97–9.10 (m, 1H); FABMS
obsd 615.3062, calcd 615.3062 (C36H47BrN4).
1
178–180 ꢀC; H NMR d 1.34 (s, 18H), 4.09 (s, 2H), 6.04–
6.08 (m, 1H), 6.09–6.13 (m, 1H), 6.14–6.17 (m, 1H),
6.55–6.59 (m, 1H), 6.78–6.82 (m, 1H), 7.61 (t, J¼1.8 Hz,
1H), 7.70 (d, J¼1.8 Hz, 2H), 8.76–8.96 (br, 1H), 10.32–
10.56 (br, 1H); 13C NMR d 27.0, 31.6, 35.2, 106.6, 108.4,
110.3, 117.9, 122.5, 123.7, 126.3, 127.9, 131.0, 138.0,
140.5, 151.2, 186.4; FABMS obsd 363.2435, calcd
363.2436 [(M+H)+, M¼C24H30N2O].
4.3.1.2. 1-(4-Methylbenzoyl)dipyrromethane (3-T).
Following the procedure described for 3-B, EtMgBr
(24.0 mL, 24 mmol, 1.0 M in THF) was added to a solution
of dipyrromethane 1a (1.46 g, 10.0 mmol) in dry THF
(10 mL) at room temperature under argon. The mixture
was stirred at room temperature for 10 min and then cooled
to ꢁ78 ꢀC. A solution of S-2-pyridyl 4-methylbenzothioate
(2-T) (2.29 g, 10.0 mmol) in dry THF (10 mL) was added.
The reaction mixture was maintained at ꢁ78 ꢀC for
30 min, whereupon the cooling bath was removed. After
1 h, the standard workup afforded a white powder (1.03 g,
4.3.1.5. Zn(II)-5-(3,5-Di-tert-butylphenyl)-17,18-di-
hydro-18,18-dimethylporphyrin (ZnC-B5). Following
the procedure for preparing chlorins,76 a solution of 6-B
(283 mg, 0.460 mmol) in CH3CN (46 mL) was treated
with Zn(OAc)2 (1.27 g, 6.90 mmol), AgOTf (355 mg,
1.38 mmol), and 2,2,6,6-tetramethylpiperidine (1.16 mL,
6.90 mmol). The reaction mixture was refluxed for 24 h.
Standard workup and chromatography [silica and hexanes/
1
CH2Cl2 (3:1)] gave a purple solid (45 mg, 17%): H NMR
d 1.51 (s, 18H), 2.03 (s, 6H), 4.55 (s, 2H), 7.73–7.75 (m,
1H), 7.93–7.96 (m, 2H), 8.58–8.60 (m, 1H), 8.62 (s, 1H),
8.68–8.71 (m, 2H), 8.73–8.75 (m, 1H), 8.76–8.78 (m, 1H),
8.86–8.88 (m, 1H), 9.08–9.10 (m, 1H), 9.62 (s, 1H);
LDMS obsd 589.25; FABMS obsd 590.2380, calcd
590.2388 (C36H38N4Zn); labs 405 (log 3¼5.50), 605
(4.89) nm; lem 609 nm.
1
39%): mp 167–169 ꢀC; H NMR d 2.43 (s, 3H), 4.08 (s,
2H), 6.03–6.06 (m, 1H), 6.08–6.12 (m, 1H), 6.14–6.17 (m,
1H), 6.53–6.56 (m, 1H), 6.80–6.83 (m, 1H), 9.04–9.20 (br,
1H), 10.72–10.88 (br, 1H); 13C NMR d 21.8, 27.0, 106.5,
108.4, 110.3, 117.8, 122.9, 128.2, 129.37, 129.39, 130.8,
136.0, 140.9, 142.8, 185.5; FABMS obsd 265.1338, calcd
265.1341 [(M+H)+, M¼C17H16N2O].
4.3.1.6.
Zn(II)-17,18-Dihydro-18,18-dimethyl-5-(4-
methylphenyl)porphyrin (ZnC-T5). Following the general
procedure for preparing chlorins,75 a solution of 3-T
(264 mg, 1.00 mmol) in 10 mL of dry THF was cooled to
ꢁ78 ꢀC under argon. NBS (178 mg, 1.00 mmol) was added,
and the reaction mixture was stirred for 1 h at ꢁ78 ꢀC.
Hexanes (50 mL) and water (50 mL) were added, and the
mixture was allowed to warm to room temperature. The
organic layer was separated. The aqueous phase was
extracted with CH2Cl2. The hexanes and CH2Cl2 extracts
were combined, dried (NaHCO3), and concentrated in
vacuo without heating, affording crude 4-T (367 mg,
4.3.1.3. 1-Bromo-9-(3,5-di-tert-butylbenzoyl)dipyrro-
methane (4-B). Following a general procedure,75 a solution
of 3-B (768 mg, 2.12 mmol) in dry THF (15 mL) was cooled
to ꢁ78 ꢀC under argon. NBS (377 mg, 2.12 mmol) was
added, and the reaction mixture was stirred for 1 h at
ꢁ78 ꢀC. Hexanes (100 mL) and water (100 mL) were added.
The mixture was allowed to warm to room temperature. The
organic layer was separated. The aqueous phase was ex-
tracted with CH2Cl2. The hexanes and CH2Cl2 extracts
were combined, dried (NaHCO3), and concentrated in vacuo

M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
3835
1
quantitative): H NMR d 2.43 (s, 3H), 4.08 (s, 2H), 6.03–
procedure,92 a sample of 11 (0.044 g, 0.20 mmol) was
dissolved in 1-aminopropane (1 mL) at room temperature.
After stirring for 1 h, the 1-aminopropane was removed by
distillation under reduced pressure. The crude product was
6.06 (m, 1H), 6.08–6.12 (m, 1H), 6.14–6.17 (m, 1H),
6.53–6.56 (m, 1H), 6.80–6.83 (m, 1H), 9.04–9.20 (br, 1H),
10.72–10.88 (br, 1H). Following the procedure for preparing
a tetrahydrobilene-a,76 a sample of crude 4-T (343 mg,
1.00 mmol) was reduced with NaBH4 (378 mg, 10.0 mmol)
in anhydrous THF/methanol (10 mL, 4:1). The resulting
solid was dissolved in anhydrous CH3CN (10 mL), to which
5 (190 mg, 1.00 mmol) and TFA (77 mL, 1.0 mmol) were
added. The reaction mixture was stirred at room temperature
for 30 min. Then 10% aqueous NaHCO3 (50 mL) was added.
The mixture was extracted with distilled CH2Cl2. The or-
ganic extract was washed with water, dried (NaHCO3),
and concentrated in vacuo without heating. The resulting
brown solid was purified by chromatography [silica and
hexanes/ethyl acetate (5:1)/ethyl acetate] to give 6-T
as a brown solid (110 mg, 21%). Following the procedure
for preparing chlorins,76 a solution of 6-T (59.3 mg,
0.115 mmol) in CH3CN (11 mL) was treated with Zn(OAc)2
(317 mg, 1.73 mmol), AgOTf (88.6 mg, 0.345 mmol), and
2,2,6,6-tetramethylpiperidine (0.29 mL, 1.7 mmol). The re-
action mixture was refluxed exposed to air for 24 h. Standard
workup and chromatography [silica and hexanes/CH2Cl2
(3:1)] gave a purple solid (19.5 mg, 34%): 1H NMR d 2.02
(s, 6H), 2.68 (s, 3H), 4.50 (s, 2H), 7.49–7.52 (m, 2H),
7.95–8.00 (m, 2H), 8.61 (s, 1H), 8.62 (s, 1H), 8.64–8.66
(m, 1H), 8.67–8.70 (m, 1H), 8.72–8.75 (m, 1H), 8.82–8.85
(m, 1H), 8.99–9.02 (m, 1H), 9.54 (s, 1H); 13C NMR
d 21.8, 31.2, 45.3, 50.5, 94.9, 96.3, 109.1, 124.4, 126.8,
127.1, 127.6, 128.1, 129.4, 132.8, 133.4, 133.9, 137.2,
139.7, 146.00, 146.01, 146.7, 147.4, 153.4, 153.7, 159.7,
170.6; LDMS obsd 491.1; FABMS obsd 492.1295, calcd
492.1292 (C29H24N4Zn); labs 405, 605 nm; lem 608 nm.
1
used in the next step without further purification: H NMR
d 0.92 (s, 3H), 0.94 (t, J¼7.4 Hz, 3H), 1.09 (s, 3H), 2.04
(m, 3H), 1.61–1.70 (m, 2H), 2.27, 2.36 (AB, J¼16.6 Hz,
2H), 2.66 (ABX, 2J¼14.8 Hz, 3J¼10.6 Hz, 1H), 2.75
2
3
(ABX, J¼14.8 Hz, J¼4.0 Hz, 1H), 3.39–3.51 (m, 2H),
3.64–3.69 (m, 1H), 5.99 (d, J¼3.8 Hz, 1H), 6.35 (d,
J¼3.8 Hz, 1H), 7.96 (s, 1H).
4.3.3. Route I.
4.3.3.1. Attempted synthesis of ZnC-P10 using TFA. A
solution of 7b (32 mg, 0.10 mmol) in THF/MeOH (40 mL,
3:1) was treated with NaBH4 (0.19 g, 5.0 mmol) and stirred
at room temperature for 30 min. TLC [silica and CH2Cl2/
ethyl acetate (5:1)] showed complete consumption of start-
ing material. The reaction was quenched by addition of sat-
urated aqueous NH4Cl (w50 mL). The resulting mixture was
extracted with ether. The organic extract was washed (water
and brine) and dried (MgSO4). Acetonitrile (1 mL) was
added, and the volatile solvent (predominantly ether) was
evaporated under low vacuum. (Note that complete evapora-
tion of solvent caused complete decomposition of the carbi-
nol.) A sample of 5 (19 mg, 0.10 mmol) was added, and the
resulting solution was treated with TFA (8 mL, 0.1 mmol).
The reaction mixture was stirred at room temperature
for 30 min and then diluted with CH3CN (9 mL). Samples
of 2,2,6,6-tetramethylpiperidine (0.506 mL, 3.00 mmol),
anhydrous Zn(OAc)2 (0.276 g, 1.50 mmol), and AgOTf
(0.077 g, 0.30 mmol) were added. The resulting mixture
was refluxed exposed to air for 20 h. The yield observed
spectroscopically was <1%. The mixture was concentrated
and filtered through silica (CH2Cl2) to afford a green solid.
Characterization data (LDMS and UV–vis) were identical
as described for ZnC-P10 (vide infra).
4.3.2. Precursors for examination of routes I–V.
4.3.2.1. 1-Bromo-9-formyl-5-phenyldipyrromethane
(8b). Following the procedure for the preparation of 8c,77
bromination of 7b (150 mg, 0.600 mmol) with NBS gave
a crude solid that upon recrystallization (EtOH/H2O, 4:1) af-
forded a light brown solid (108 mg, 55%): mp 133 ꢀC (dec);
1H NMR (THF-d8) d 5.42 (s, 1H), 5.59–5.61 (m, 1H), 5.86–
5.88 (m, 1H), 5.92–5.94 (m, 1H), 6.79–6.81 (m, 1H), 7.16–
7.30 (m, 5H), 9.40 (s, 1H), 10.51 (br, 1H), 11.21 (br, 1H); 13C
NMR d 44.3, 97.2, 109.3, 109.5, 110.3, 120.4, 126.9, 128.3,
128.5, 133.5, 133.8, 141.7, 142.2, 177.9. Anal. Calcd for
C16H13BrN2O: C, 58.38; H, 3.98; N, 8.51. Found: C,
58.31; H, 3.92; N, 8.45.
4.3.3.2. Attempted synthesis of ZnC using BF3$O(Et)2.
A solution of 5 (38.0 mg, 0.198 mmol) and 8a (50.0 mg,
0.198 mmol) in dry CH3CN (1.98 mL) was treated with
BF3$O(Et)2 (25.0 mL, 0.198 mmol) and stirred for 15 min
at room temperature. No reaction occurred upon examina-
tion by TLC, whereupon additional BF3$O(Et)2 (50.0 mL)
was added. The mixture was stirred for 20 min, quenched
with water and extracted with CH2Cl2. The solvent was
removed under reduced pressure to give a brown oil. TLC
1
analysis and H NMR spectroscopy of the crude mixture
revealed only starting material 8a.
4.3.2.2. 1-Bromo-9-formyl-5-phenyldipyrrin (10b). A
solution of 8b (0.033 g, 1.0 mmol) in CHCl3 (2 mL) was
treated with a suspension of DDQ (0.027 g, 1.0 mmol) in
CHCl3 (1 mL). The mixture was stirred at room temperature
for 1 h. The mixture was concentrated. The residue was
chromatographed (silica and CH2Cl2) to afford an orange
4.3.4. Route II.
4.3.4.1. Condensation study. A solution of 5 (10.0 mg,
39.5 mmol) and 8a (7.50 mg, 39.5 mmol) in CH2Cl2 under ar-
gon was treated with p-TsOH$H2O (37.6 mg, 0.198 mmol)
in MeOH. The quantity of each of 5, 8a, and p-TsOH$H2O
was identical in each experiment, while the quantity of
solvent was varied from 5.7 mL (6.9 mM) to 0.77 mL
(51 mM). In each case, the ratio of CH2Cl2/methanol was
held constant at 4:1. For example, samples of 5 and 8a
were dissolved in CH2Cl2 (2.34 mL) and subsequently
treated with p-TsOH$H2O in MeOH (0.59 mL) to give the
desired concentration of 13.5 mM. The mixture was stirred
for 30 min under argon and quenched by addition of 10%
1
solid (0.016 g, 50%): mp 121–123 ꢀC; H NMR d 6.35 (d,
J¼4.4 Hz, 1H), 6.20 (d, J¼4.4 Hz, 1H), 6.75 (d, J¼4.4 Hz,
1H), 6.88 (d, J¼4.4 Hz, 1H), 7.42–7.52 (m, 5H), 9.72 (s,
1H); 13C NMR d 119.7, 121.7, 128.3, 129.7, 129.8, 130.9,
137.6, 138.9, 150.6, 152.2, 180.3; FABMS obsd 327.0129,
calcd 327.0133 [(M+H)+, M¼C16H11N2OBr]; labs 437 nm.
4.3.2.3. 2,3,4,5-Tetrahydro-9-(N-propyliminomethyl)-
1,3,3-trimethyldipyrrin (PrN-8b). Following a general

3836
M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
aqueous NaHCO3 (10 mL). After extracting the mixture
with CH2Cl2, the extract was dried (Na2SO4) and filtered.
The filtrate was concentrated to give a brown solid. The
crude solid was dissolved in CH3CN (4 mL, 10 mM assum-
ing quantitative formation) and treated with Zn(OAc)2
(109 mg, 0.593 mmol), AgOTf (30.4 mg, 0.119 mmol),
and 2,2,6,6-tetramethylpiperidine (0.101 mL, 0.593 mmol).
The reaction mixture was heated at 70 ꢀC for 19 h exposed
to air. The mixture was concentrated. The resulting black
residue was chromatographed (silica and CH2Cl2), affording
a bluish-green solid. The isolated chlorin yield was then
recorded after drying under vacuum, affording 1.8 mg
(11%) of ZnC.
change (typically 5–10 h). The mixture was concentrated.
The resulting black mixture was chromatographed [silica
and hexanes/CH2Cl2 (1:1)] to afford a blue-green solid
(0.145 g, 18%). The characterization data (1H NMR, 13C
NMR, LDMS, FABMS, and UV–vis) were consistent with
those reported previously.77
4.3.4.4. AgOTf-free Route II: Pd(II)-17,18-dihydro-
18,18-dimethylporphyrin (PdC). Following the AgOTf-
free route II, samples of 5 (95 mg, 0.50 mmol) and 8a
(126 mg, 0.500 mmol) were dissolved in CH2Cl2 (15 mL).
A solution of p-TsOH$H2O (475.0 mg, 2.50 mmol) in an-
hydrous MeOH (5 mL) was added. The resulting mixture
was stirred for 30 min and then treated with 2,2,6,6-tetra-
methylpiperidine (2.50 mL). The mixture was concentrated.
The resulting yellow solid was dissolved in CH3CN
(50 mL). Samples of 2,2,6,6-tetramethylpiperidine (2.54 mL,
15.0 mmol) and Pd(OAc)2 (0.338 g, 1.50 mmol) were
added. The resulting mixture was refluxed exposed to air
for 1 h. The resulting dark-green mixture was concentrated
and chromatographed [silica and hexanes/CH2Cl2 (1:1)] to
A study of the concentration dependence of the condensation
conditions where 5 mol equiv of p-TsOH$H2O was em-
ployed led to the following yields of ZnC: 10% (7 mM),
11% (14 mM), 22% (26 mM), and 22% (51 mM).
4.3.4.2. Route II: Zn(II)-17,18-dihydro-18,18-
dimethyl-10-phenylporphyrin (ZnC-P10). A mixture of
8b (0.165 g, 0.500 mmol) and 5 (0.095 g, 0.50 mmol) in
dry CH2Cl2 (10.8 mL) was treated with a solution of
p-TsOH$H2O (0.475 g, 2.50 mmol) in anhydrous MeOH
(8.25 mL). The resulting red solution was stirred at room
temperature for 30 min. A sample of 2,2,6,6-tetramethyl-
piperidine (0.630 mL, 3.71 mmol) was added. The mixture
was concentrated. The resulting yellow solid was dissolved
in CH3CN (50 mL). Samples of 2,2,6,6-tetramethylpiperi-
dine (2.10 mL, 12.4 mmol), anhydrous Zn(OAc)2 (1.37 g,
7.50 mmol), and AgOTf (0.385 g, 1.50 mmol) were added.
The mixture was refluxed in the presence of air for 20 h.
The mixture was concentrated. The resulting black residue
was chromatographed [silica and CH2Cl2/hexanes (1:1)] to
1
afford a violet-green solid (7.5 mg, 3%): H NMR d 2.02
(s, 6H), 4.62 (s, 2H), 8.98 (d, J¼4.4 Hz, 1H), 8.73 (s, 1H),
8.74 (d, J¼4.4 Hz, 1H), 8.81 (s, 1H), 8.95–8.96 (m, 2H),
8.98 (d, J¼4.4 Hz, 1H), 8.99 (d, J¼4.4 Hz, 1H), 9.72
(s, 1H), 9.74 (s, 1H); LDMS obsd 443.7; FABMS
obsd 444.0557, calcd 444.0566 (C22H18N4Pd); labs 388,
585 nm.
4.3.4.5.
Cu(II)-17,18-Dihydro-18,18-dimethylpor-
phyrin (CuC). Following the AgOTf-free route II, samples
of 5 (19.0 mg, 100 mmol) and 8a (25.3 mg, 100 mmol) were
dissolved in CH2Cl2 (3 mL). A solution of p-TsOH$H2O
(95.0 mg, 500 mmol) in anhydrous MeOH (1 mL) was
added. The resulting mixture was stirred for 30 min and then
neutralized with 2,2,6,6-tetramethylpiperidine (500 mL). The
mixture was concentrated. The resulting yellow solid was
dissolved in EtOH (4 mL). Samples of Cu(OAc)2
(39.2 mg, 200 mmol) and KOH (42.0 mg, 750 mmol) were
added. The resulting mixture was refluxed exposed to air
for 21 h. The resulting mixture was concentrated and chro-
matographed (silica/CH2Cl2) to afford a green solid
(2.2 mg, 5%): LDMS obsd 400.6; FABMS obsd 401.0837,
calcd 401.0827 (C22H18N4Cu); labs 396, 598 nm.
1
afford a violet-green solid (79 mg, 33%): H NMR d 2.04
(s, 6H), 4.53 (s, 2H), 7.67–7.72 (m, 3H), 8.08–8.10 (m,
2H), 8.52 (d, J¼4.5 Hz, 1H), 8.62–8.64 (m, 2H), 8.69–
8.70 (m, 2H), 8.78 (d, J¼4.1 Hz, 1H), 8.86 (d, J¼4.1 Hz,
1H), 9.09 (d, J¼4.1 Hz, 1H), 9.62 (s, 1H); 13C NMR
d 31.0, 45.4, 50.4, 94.3, 97.0, 109.4, 123.8, 126.79,
126.84, 127.3, 127.6, 128.2, 129.2, 132.9, 133.3, 133.9,
142.6, 145.86, 145.97, 146.5, 147.4, 153.1, 154.0, 159.2,
171.0; LDMS obsd 477.8; ESI-MS obsd 478.1154, calcd
478.1136 (C28H22N4Zn); labs 405 (log 3¼5.44), 605
(4.83) nm; lem 608 nm.
4.3.4.6.
Pd(II)-17,18-Dihydro-18,18-dimethyl-10-
4.3.4.3. Streamlined route II (ZnC). A solution of 7a
(344 mg, 2.00 mmol) in THF (40 mL) was treated with
NBS (356 mg, 2.00 mmol) at ꢁ78 ꢀC. After 1 h the mixture
was allowed to warm to ꢁ20 ꢀC. A mixture of water (30 mL)
and hexanes (30 mL) was added. Excess CH2Cl2 was added.
The organic layer was separated, dried (Na2SO4), and con-
centrated. The resulting solid was dissolved in dry CH2Cl2
(43 mL), to which a sample of 5 (0.360 g, 2.00 mmol) and
a solution of p-TsOH$H2O (1.92 g, 10.0 mmol) in MeOH
(33 mL) were added. The red mixture was stirred for
phenylporphyrin (PdC-P10). Samples of 5 (19.0 mg,
100 mmol) and 8b (32.6 mg, 100 mmol) were dissolved in
CH2Cl2 (3 mL). A solution of p-TsOH$H2O (95.0 mg,
500 mmol) in anhydrous MeOH (1 mL) was added. The re-
sulting mixture was stirred for 30 min and then neutralized
with 2,2,6,6-tetramethylpiperidine (500 mL). The mixture
was concentrated. The resulting yellow solid was dissolved
in CH3CN (10 mL). Samples of 2,2,6,6-tetramethylpiper-
idine (0.509 mL, 3.00 mmol) and Pd(OAc)2 (0.338 g,
1.50 mmol) were added. The resulting mixture was refluxed
exposed to air for 1 h. The resulting dark-green mixture was
concentrated and chromatographed (silica and CH2Cl2) to
30 min.
A
sample of 2,2,6,6-tetramethylpiperidine
(2.52 mL, 14.8 mmol) was added. The mixture was concen-
trated. The residue was dissolved in CH3CN (200 mL). An-
hydrous Zn(OAc)2 (5.52 g, 30.0 mmol), AgOTf (1.55 g,
6.00 mmol), and 2,2,6,6-tetramethylpiperidine (8.40 mL,
49.5 mmol) were added. The mixture was refluxed exposed
to air until the absorption spectrum showed no further
1
afford a violet solid (6.0 mg, 12%): H NMR d 2.02 (s,
6H), 4.60 (s, 2H), 7.69–7.72 (m, 3H), 8.04–8.07 (m, 2H),
8.53 (d, J¼4.8 Hz, 1H), 8.57–8.58 (m, 2H), 8.69 (s, 1H),
8.72 (d, J¼4.8 Hz, 1H), 8.79 (s, 1H), 8.84 (d, J¼4.8 Hz,
1H), 8.96 (d, J¼4.8 Hz, 1H), 9.69 (s, 1H); LDMS obsd

M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
3837
1
519.9; FABMS obsd 520.0901, calcd 520.0879
(C28H22N4Pd); labs 394, 587 nm.
The H NMR and LDMS data showed the presence of a
significant amount of bromochlorins.
4.3.4.7. Cu(II)-17,18-Dihydro-18,18-dimethyl-10-phe-
nylporphyrin (CuC-P10). Following the AgOTf-free route
II, samples of 5 (19.0 mg, 100 mmol) and 8b (32.9 mg,
100 mmol) were dissolved in CH2Cl2 (3 mL). A solution of
p-TsOH$H2O (95.0 mg, 500 mmol) in anhydrous MeOH
(1 mL) was added. The resulting mixture was stirred for
30 min and then neutralized with 2,2,6,6-tetramethyl-
piperidine (500 mL). The mixture was concentrated. The
resulting yellow solid was dissolved in EtOH (5 mL). Sam-
ples of KOH (42 mg, 0.75 mmol) and Cu(OAc)2 (37.2 mg,
0.200 mmol) were added. The resulting mixture was re-
fluxed exposed to air for 21 h. The resulting dark-green mix-
ture was concentrated and chromatographed [silica,
hexanes/CH2Cl2 (1:1)] to afford a green solid (7.3 mg,
15%): LDMS 476.9; FABMS obsd 477.1153, calcd
477.1140 (C28H22N4Cu); labs 394, 587 nm.
Acknowledgements
This work was supported by the NIH (GM36238). Mass
spectra were obtained at the Mass Spectrometry Laboratory
for Biotechnology at North Carolina State University. Partial
funding for the facility was obtained from the North
Carolina Biotechnology Center and the NSF.
References and notes
1. Smith, J. H. C.; Benitez, A. Modern Methods of Plant Analysis;
Paech, K., Tracey, M. V., Eds.; Springer: Berlin, 1955; Vol. IV,
pp 142–196.
2. Strain, H. H.; Thomas, M. R.; Katz, J. J. Biochim. Biophys. Acta
1963, 75, 306–311.
4.3.5. Routes III and IV.
3. (a) Wang, J.-J. Chin. J. Org. Chem. 2005, 25, 1353–1371; (b)
Pavlov, V. Y.; Ponomarev, G. V. Chem. Heterocycl. Compd.
2004, 40, 393–425; (c) Pandey, R. K.; Zheng, G. The Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.;
Academic: San Diego, CA, 2000; Vol. 6, pp 157–230; (d)
Hynninen, P. H. Chlorophylls; Scheer, H., Ed.; CRC: Boca
Raton, FL, 1991; pp 145–209.
4. (a) Vicente, M. G. H. The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic: San Diego, CA,
2000; Vol. 1, pp 149–199; (b) Jaquinod, L. The Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.;
Academic: San Diego, CA, 2000; Vol. 1, pp 201–237.
5. Dorough, G. D.; Huennekens, F. M. J. Am. Chem. Soc. 1952,
74, 3974–3976.
4.3.5.1. General procedure for attempted chlorin
formation. Samples of an Eastern half (0.10 mmol) and
a Western half (0.10 mmol) were dissolved in anhydrous
CH2Cl2 (4 mL) and treated with p-TsOH$H2O (0.095 g,
0.50 mmol). The resulting mixture was stirred for 15 min
at room temperature. The reaction was quenched by addition
of 10% aqueous NaHCO3. The resulting mixture was
extracted with CH2Cl2. The organic phase was washed
with water and brine, dried (Na2SO4), and concentrated.
The residue was dissolved in CH3CN (10 mL) and treated
with anhydrous Zn(OAc)2 (0.276 g, 1.50 mmol), AgOTf
(0.077 g, 0.30 mmol), and 2,2,6,6-tetramethylpiperidine
(0.504 mL, 3.00 mmol). The reaction mixture was refluxed
for 20 h exposed to air, during which time the spectroscopic
yield of chlorin was checked. This procedure was applied for
the reaction of 12c+11 to give ZnC-M10 (8% yield), and
10b+5 to give ZnC-P10 (<1% yield).
6. Eisner, U. J. Chem. Soc. 1957, 3461–3469.
7. (a) Wang, T. Y.; Chen, J. R.; Ma, J. S. Dyes Pigments 2002, 52,
199–208; (b) Shan, X.; Wang, T.; Li, S.; Yang, L.; Fu, L.; Yang,
G.; Wang, Z.; Ma, J. S. J. Photochem. Photobiol. B 2006, 82,
140–145.
4.3.6. Route V.
8. Bonnett, R.; Djelal, B. D.; Nguyen, A. J. Porphyrins Phthalo-
cyanines 2001, 5, 652–661.
4.3.6.1.
Zn(II)-17,18-Dihydro-18,18-dimethyl-10-
phenylporphyrin (ZnC-P10). A solution of 1b (0.111 g,
0.500 mmol) and 11 (0.109 g, 0.500 mmol) in CH2Cl2
(15 mL) was treated with a solution of p-TsOH$H2O
(0.478 g, 2.5 mmol) in MeOH (5 mL). The resulting mixture
was stirred at room temperature for 30 min. The reaction
mixture was neutralized with excess triethylamine, washed
with water and brine, dried (Na2SO4), and concentrated to
afford crude 9b as an orange solid. Crude 9b was dissolved
in dry THF (5 mL) and treated with NBS (0.089 g,
0.50 mmol) at ꢁ78 ꢀC. The reaction mixture was stirred at
ꢁ78 ꢀC for 1 h, allowed to warm to w ꢁ20 ꢀC, and then
quenched by addition of a mixture of hexanes (5 mL) and
water (5 mL). The resulting mixture was extracted with
CH2Cl2. The organic extract was washed with water and
brine, dried (Na2SO4) and concentrated to afford the crude
19-bromotetrahydrobiladiene (9b-Br) as a brown solid.
The crude 9b-Br was dissolved in CH3CN (50 mL), to which
anhydrous Zn(OAc)2 (1.38 g, 7.50 mmol), AgOTf (0.385 g,
1.50 mmol), and 2,2,6,6-tetramethylpiperidine (2.52 mL,
15.0 mmol) were added. The reaction mixture was refluxed
for 20 h. Standard workup and chromatography [silica and
hexanes/CH2Cl2 (1:1)] gave a bluish-green solid (15 mg).
9. Bruckner, C.; Dolphin, D. Tetrahedron Lett. 1995, 36, 3295–
€
3298.
10. (a) Sutton, J. M.; Fernandez, N.; Boyle, R. W. J. Porphyrins
Phthalocyanines 2000, 4, 655–658; (b) Wang, T. Y.; Liu,
H. L.; Chen, J. R.; Liu, F. G.; Gu, Y.; Ma, J. S. Bioorg. Med.
Chem. Lett. 2001, 11, 2049–2052; (c) Sutton, J. M.; Clarke,
O. J.; Fernandez, N.; Boyle, R. W. Bioconjugate Chem. 2002,
ꢀ
13, 249–263; (d) Ferrand, Y.; Bourre, L.; Simonneaux, G.;
Thibaut, S.; Odobel, F.; Lajat, Y.; Patrice, T. Bioorg. Med.
Chem. Lett. 2003, 13, 833–835.
11. (a) Kuz’mitskii, V. A. J. Appl. Spectrosc. 2005, 72, 360–370;
(b) Linnanto, J.; Korppi-Tommola, J. Phys. Chem. Chem.
€
Phys. 2000, 2, 4962–4970; (c) Almlof, J.; Fischer, T. H.;
Gassman, P. G.; Ghosh, A.; Haser, M. J. Phys. Chem. 1993,
97, 10964–10970.
€
12. Sevchenko, A. N.; Solov’ev, K. N.; Shkirman, S. F.;
Sarzhevskaya, M. V. Dokl. Akad. Nauk SSSR 1963, 1391–
1394 (Eng. Translation pp 1151–1155).
13. Sevchenko, A. N.; Solov’ev, K. N.; Mashenkov, V. A.;
Shkirman, S. F. Sov. Phys. Dokl. 1966, 10, 778–780.
14. Gradyushko, A. T.; Sevchenko, A. N.; Solovyov, K. N.;
Tsvirko, M. P. Photochem. Photobiol. 1970, 11, 387–400.

3838
M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
15. Solov’ev, K. N.; Mashenkov, V. A.; Gradyushko, A. T.;
Turkova, A. E.; Lezina, V. P. Zh. Prikl. Specktr. 1970, 13,
339–345 (Eng. Translation pp 1106–1111).
16. Spectroscopy of Chlorophyll and Related Compounds. In
National Technical Information Service; Gurinovich, G. P.,
Sevchenko, A. N., Solov’ev, K. N., Eds.; US Department of
Commerce: Springfield, VA, 1971; pp 330–332.
17. Sinyakov, G. N.; Poznyak, A. L.; Gurinovich, G. P. Zh. Prikl.
Specktr. 1972, 16, 732–734 (Eng. Translation pp 543–545).
18. van der Bent, S. J.; de Jager, A.; Schaafsma, T. J. Rev. Sci.
Instrum. 1976, 47, 117–121.
19. van der Bent, S. J.; Schaafsma, T. J. J. Chem. Phys. 1978, 68,
1857–1861.
43. Dzilinski, K.; Synyakov, G. N.; Shulga, A. M.; Filatov, I. V.;
Gurinovich, G. P. Radiat. Phys. Chem. 1995, 45, 923–928.
44. Shulga, A. M.; Sinyakov, G. N.; Filatov, I. V.; Gurinovich,
G. P.; Dzilinski, K. Biospectroscopy 1995, 1, 223–234.
45. Maniloff, E. S.; Graf, F. R.; Gygax, H.; Altner, S. B.; Bernet, S.;
Renn, A.; Wild, U. P. Chem. Phys. 1995, 193, 173–180.
€
46. Muschenborn, H.-J.; Wild, U. P. Optoelectron.–Devices
Technol. 1995, 10, 311–332.
47. Huang, W.-Y.; Riper, E. V.; Johnson, L. W. Spectrochim. Acta
Part A 1996, 52, 761–769.
48. Kikas, J.; Suisalu, A.; Zazubovich, V. Mol. Cryst. Liq. Cryst.
1996, 291, 215–222.
49. den Hartog, F. T. H.; Bakker, M. P.; Koedijk, J. M. A.;
€
€
Creemers, T. M. H.; Volker, S. J. Lumin. 1996, 66 & 67,
20. Volker, S.; Macfarlane, R. M. J. Chem. Phys. 1980, 73, 4476–
4482.
1–7.
50. Altmann, R. B.; Kador, L.; Haarer, D. Chem. Phys. 1996, 202,
167–174.
21. Dicker, A. I. M.; Noort, M.; Thijssen, H. P. H.; Volker, S.; van
der Waals, J. H. Chem. Phys. Lett. 1981, 78, 212–218.
€
22. Dicker, A. I. M.; Dobkowski, J.; Noort, M.; Volker, S.; van der
51. Kikas, J.; Suisalu, A.; Zazubovich, V.; Vois, P. J. Chem. Phys.
1996, 104, 4434–4440.
52. Huang, W.-Y.; Rebane, A.; Wild, U. P.; Johnson, L. W.
J. Lumin. 1997, 71, 237–243.
53. Zazubovich, V.; Suisalu, A.; Kikas, J. J. Lumin. 1998, 76 & 77,
615–618.
€
54. den Hartog, F. T. H.; Bakker, M. P.; Silbey, R. J.; Volker, S.
Waals, J. H. Chem. Phys. Lett. 1982, 88, 135–137.
23. Keegan, J. D.; Stolzenberg, A. M.; Lu, Y.-C.; Linder, R. E.;
Barth, G.; Moscowitz, A.; Bunnenberg, E.; Djerassi, C.
J. Am. Chem. Soc. 1982, 104, 4317–4329.
24. Dicker, A. I. M.; Johnson, L. W.; Noort, M.; van der Waals,
J. H. Chem. Phys. Lett. 1983, 94, 14–20.
25. Burkhalter, F. A.; Suter, G. W.; Wild, U. P.; Samoilenko, V. D.;
Rasumova, N. V.; Personov, R. I. Chem. Phys. Lett. 1983, 94,
483–487.
Chem. Phys. Lett. 1998, 297, 314–320.
55. Suisalu, A.; Zazubovich, V.; Kikas, J.; Friebel, J.; Friedrich, J.
Europhys. Lett. 1998, 44, 613–619.
26. Gladkov, L. L.; Ksenofontova, N. M.; Solov’ev, K. N.;
Starukhin, A. S.; Shul’ga, A. M.; Gradyushko, A. T. Zh.
Prikl. Specktr. 1983, 38, 598–605 (Eng. Translation pp 435–
440).
27. Arabei, S. M.; Egorova, G. D.; Solov’ev, K. N.; Shkirman, S. F.
Zh. Prikl. Specktr. 1986, 44, 117–123 (Eng. Translation pp 96–
100).
28. Avarmaa, R. A.; Rebane, K. K. Spectrochim. Acta 1985, 41A,
1365–1380.
29. Dzilinski, K.; Sinyakov, G. N.; Shul’ga, A. M.; Zotov, N. I.
J. Struct. Chem. 1990, 31, 227–231.
30. Ellervee, A.; Jaaniso, R.; Kikas, J.; Laisaar, A.; Suisalu, A.;
Shcherbakov, V. Chem. Phys. Lett. 1991, 176, 472–476.
31. De Caro, C.; Renn, A.; Wild, U. P. Appl. Optics 1991, 30,
2890–2898.
32. Ellervee, A.; Hizhnyakov, V. V.; Kikas, J.; Laisaar, A.; Suisalu,
A. J. Lumin. 1992, 53, 223–226.
33. Kulikov, S.; Galaup, J. P. J. Lumin. 1992, 53, 239–243.
34. Al’shits, E. I.; Kharlamov, B. M.; Ulitsky, N. I. J. Opt. Soc.
Am. B 1992, 9, 950–955.
35. Ellervee, A.; Kikas, J.; Laisaar, A.; Shcherbakov, V.; Suisalu,
A. J. Opt. Soc. Am. B 1992, 9, 972–977.
56. Kikas, J.; Laisaar, A.; Suisalu, A.; Kuznetsov, A.; Ellervee, A.
Phys. Rev. B 1998, 57, 14–17.
€
57. den Hartog, F. T. H.; van Papendrecht, C.; Silbey, R. J.; Volker,
S. J. Chem. Phys. 1999, 110, 1010–1016.
58. Singh, A.; Huang, W.-Y.; Johnson, L. W. J. Phys. Chem. A
2000, 104, 894–898.
59. Drobizhev, M.; Karotki, A.; Rebane, A. Chem. Phys. Lett.
2001, 334, 76–82.
60. Singh, A.; Huang, W.-Y.; Egbujor, R.; Johnson, L. W. J. Phys.
Chem. A 2001, 105, 5778–5784.
61. Zazubovich, V.; Suisalu, A.; Kikas, J. Phys. Rev. B 2001,
64, 1–7.
62. Singh, A.; Johnson, L. W. Spectrochim. Acta Part A 2002, 58,
1573–1576.
63. Singh, A.; Huang, W.-Y.; Johnson, L. W. Spectrochim. Acta
Part A 2002, 58, 2177–2183.
64. Renge, I. J. Lumin. 2002, 98, 213–220.
65. Karotki, A.; Kruk, M.; Drobizhev, M.; Rebane, A. J. Mod. Opt.
2002, 49, 379–390.
66. Renn, A.; Wild, U. P.; Rebane, A. J. Phys. Chem. A 2002, 106,
3045–3060.
67. Berezin, K. V.; Nechaev, V. V. Chem. Nat. Compd. 2003, 39,
540–548.
68. Renge, I. Chem. Phys. 2003, 295, 255–268.
69. Berezin, K. V.; Nechaev, V. V. Opt. Spectrosc. 2004, 97,
707–713.
36. Al’shits, E. I.; Kharlamov, B. M.; Ulitsky, N. I.; Nekhaev, D. V.
Chem. Phys. 1992, 163, 405–411.
37. Miles, J. R.; Sarre, P. J. J. Chem. Soc., Faraday Trans. 1992, 88,
1075–1076.
38. Miles, J. R.; Sarre, P. J. J. Chem. Soc., Faraday Trans. 1993, 89,
2269–2276.
39. Ellervee, A.; Kikas, J.; Laisaar, A.; Suisalu, A. J. Lumin. 1993,
56, 151–156.
70. Eisner, U.; Linstead, R. P. J. Chem. Soc. 1955, 3749–3754.
71. Eisner, U.; Linstead, R. P. J. Chem. Soc. 1955, 3742–3749.
72. Egorova, G. D.; Solov’ev, K. N.; Shul’ga, A. M. J. Gen. Chem.
USSR 1967, 37, 333–336.
40. Kikas, J.; Schellenberg, P.; Friedrich, J. Chem. Phys. Lett.
1993, 207, 143–147.
73. Seely, G. R.; Talmadge, K. Photochem. Photobiol. 1964, 3,
195–206.
€
74. Montforts, F.-P.; Gerlach, B.; Hoper, F. Chem. Rev. 1994, 94,
41. Schellenberg, P.; Friedrich, J.; Kikas, J. J. Chem. Phys. 1994,
100, 5501–5507.
42. Shulga, A. M.; Sinyakov, G. N.; Filatov, I. V.; Gurinovich,
G. P.; Dzilinski, K. J. Mol. Struct. 1995, 348, 65–68.
327–347.
75. Strachan, J.-P.; O’Shea, D. F.; Balasubramanian, T.; Lindsey,
J. S. J. Org. Chem. 2000, 65, 3160–3172.

M. Ptaszek et al. / Tetrahedron 63 (2007) 3826–3839
3839
76. Taniguchi, M.; Ra, D.; Mo, G.; Balasubramanian, T.; Lindsey,
J. S. J. Org. Chem. 2001, 66, 7342–7354.
90. Sharada, D. S.; Muresan, A. Z.; Muthukumaran, K.; Lindsey,
J. S. J. Org. Chem. 2005, 70, 3500–3510.
77. Laha, J. K.; Muthiah, C.; Taniguchi, M.; McDowell, B. E.;
Ptaszek, M.; Lindsey, J. S. J. Org. Chem. 2006, 71, 4092–
4102.
91. Rosenfeld, A.; Morgan, J.; Goswami, L. N.; Ohulchanskyy, T.;
Zheng, X.; Prasad, P. N.; Oseroff, A.; Pandey, R. K.
Photochem. Photobiol. 2006, 82, 626–634.
78. O’Neal, W. G.; Roberts, W. P.; Ghosh, I.; Wang, H.; Jacobi,
P. A. J. Org. Chem. 2006, 71, 3472–3480.
79. Balasubramanian, T.; Strachan, J. P.; Boyle, P. D.; Lindsey, J. S.
J. Org. Chem. 2000, 65, 7919–7929.
80. Taniguchi, M.; Kim, M. N.; Ra, D.; Lindsey, J. S. J. Org. Chem.
2005, 70, 275–285.
81. Taniguchi, M.; Ptaszek, M.; McDowell, B. E.; Lindsey, J. S.
Tetrahedron 2007, 63, 3840–3849.
82. Taniguchi, M.; Ptaszek, M.; McDowell, B. E.; Boyle, P. D.;
Lindsey, J. S. Tetrahedron 2007, 63, 3850–3863.
83. Rao, P. D.; Dhanalekshmi, S.; Littler, B. J.; Lindsey, J. S.
J. Org. Chem. 2000, 65, 7323–7344.
84. Laha, J. K.; Dhanalekshmi, S.; Taniguchi, M.; Ambroise, A.;
Lindsey, J. S. Org. Process Res. Dev. 2003, 7, 799–812.
85. Zaidi, S. H. H.; Muthukumaran, K.; Tamaru, S.-I.; Lindsey,
J. S. J. Org. Chem. 2004, 69, 8356–8365.
92. Taniguchi, M.; Balakumar, A.; Fan, D.; McDowell, B. E.;
Lindsey, J. S. J. Porphyrins Phthalocyanines 2005, 9, 554–574.
93. (a) Sapunov, V. V.; Egorova, G. D. J. Appl. Spectrosc. 1987, 46,
519–522; (b) Stolzenberg, A. M.; Schussel, L. J.; Summers,
J. S.; Foxman, B. M.; Petersen, J. L. Inorg. Chem. 1992, 31,
1678–1686; (c) Singh, A.; Johnson, L. W. Spectrochim. Acta
Part A 2003, 59, 905–908.
94. (a) Borisevich, E. A.; Egorova, G. D.; Knyukshto, V. N.;
Solovev, K. N. Opt. Spectrosc. (USSR) 1984, 56, 255–258;
(b) Lomova, T. N.; Mozhzhukhina, E. G.; Shormanova, L. P.;
Berezin, B. D. J. Gen. Chem. USSR 1989, 54, 2077–2084; (c)
Sengupta, D.; Robinson, B. C. Tetrahedron 2002, 58, 5497–
5502; (d) Ciulla, T. A.; Criswell, M. H.; Danis, R. P.; Snyder,
W. J.; Small, W., IV. Retina 2004, 24, 521–529; (e) Ciulla,
T. A.; Criswell, M. H.; Snyder, W. J.; Small, W., IV. Br. J.
Ophthalmol. 2005, 89, 113–119.
86. Geier, G. R., III; Littler, B. J.; Lindsey, J. S. J. Chem. Soc.,
Perkin Trans. 2 2001, 701–711.
87. Ptaszek, M.; McDowell, B. E.; Lindsey, J. S. J. Org. Chem.
2006, 71, 4328–4331.
95. Yu, L.; Muthukumaran, K.; Sazanovich, I. V.; Kirmaier, C.;
Hindin, E.; Diers, J. R.; Boyle, P. D.; Bocian, D. F.; Holten,
D.; Lindsey, J. S. Inorg. Chem. 2003, 42, 6629–6647.
96. Kim, H.-J.; Dogutan, D. K.; Ptaszek, M.; Lindsey, J. S.
Tetrahedron 2007, 63, 37–55.
€
88. Bruckner, C.; Posakony, J. J.; Johnson, C. K.; Boyle, R. W.;
James, B. R.; Dolphin, D. J. Porphyrins Phthalocyanines
1998, 2, 455–465.
89. Battersby, A. R.; Fookes, C. J. R.; Snow, R. J. J. Chem. Soc.,
Perkin Trans. 1 1984, 2725–2732.
97. Srinivasan, N.; Haney, C. A.; Lindsey, J. S.; Zhang, W.; Chait,
B. T. J. Porphyrins Phthalocyanines 1999, 3, 283–291.
98. Ptaszek, M.; Bhaumik, J.; Kim, H.-J.; Taniguchi, M.; Lindsey,
J. S. Org. Process Res. Dev. 2005, 9, 651–659.