Regioselective β-pyrrolic electrophilic substitution of hydrodipyrrin-dialkylboron complexes facilitates access to synthetic models for chlorophyll f

Article abstract of DOI:10.1039/c3nj01508d

Substituents in ring A of chlorophylls can exert profound effects on spectral properties. A de novo route to synthetic chlorins employs a tetrahydrodipyrrin reactant containing pyrrole and pyrroline rings. Complexation of the tetrahydrodipyrrin with a dialkylboron motif caused electrophilic substitution (bromination, formylation) to proceed predominantly at the β⁷- rather than α-position of the pyrrole ring, whereas an analogous dihydrodipyrrin underwent substitution equally at the 7- and 8-positions. The fully unsaturated dipyrrin-difluoroboron complex is known to undergo electrophilic substitution at the 8-position. The 7-position of the hydrodipyrrin ultimately gives rise to substituents at the chlorin 2-position (ring A), which heretofore has been little accessed. The position of substitution was confirmed by four single-crystal X-ray structures. Two isomeric formylchlorins were prepared by Pd-mediated carbonylation of the corresponding bromochlorins. Access to a 2-formylchlorin relied on bromination of the tetrahydrodipyrrin-dibutylboron complex, whereas a 3-formylchlorin was prepared by installation of the bromo group in the earliest precursor, pyrrole-2-carboxaldehyde. The two formylchlorins differ in absorption spectral properties: the Q_y absorption maximum is 654 or 664 nm for the 2- or 3-formylchlorin, respectively. The synthetic formylchlorins provide initial models for understanding the strong red absorption of native 2- or 3-formylchlorophylls (f and d).

Full text of DOI:10.1039/c3nj01508d

NJC
View Article Online
View Journal | View Issue
PAPER
Regioselective b-pyrrolic electrophilic substitution
of hydrodipyrrin–dialkylboron complexes
facilitates access to synthetic models for
chlorophyll f†
Cite this: New J. Chem., 2014,
38, 1717
Mengran Liu, Marcin Ptaszek, Olga Mass, Daniel F. Minkler, Roger D. Sommer,
Jayeeta Bhaumik and Jonathan S. Lindsey*
Substituents in ring A of chlorophylls can exert profound effects on spectral properties. A de novo route to
synthetic chlorins employs a tetrahydrodipyrrin reactant containing pyrrole and pyrroline rings. Complexation of
the tetrahydrodipyrrin with a dialkylboron motif caused electrophilic substitution (bromination, formylation) to
proceed predominantly at the b7- rather than a-position of the pyrrole ring, whereas an analogous
dihydrodipyrrin underwent substitution equally at the 7- and 8-positions. The fully unsaturated dipyrrin–difluoro-
boron complex is known to undergo electrophilic substitution at the 8-position. The 7-position of the
hydrodipyrrin ultimately gives rise to substituents at the chlorin 2-position (ring A), which heretofore has been
little accessed. The position of substitution was confirmed by four single-crystal X-ray structures. Two isomeric
formylchlorins were prepared by Pd-mediated carbonylation of the corresponding bromochlorins. Access
to a 2-formylchlorin relied on bromination of the tetrahydrodipyrrin–dibutylboron complex, whereas a
3-formylchlorin was prepared by installation of the bromo group in the earliest precursor, pyrrole-2-
carboxaldehyde. The two formylchlorins differ in absorption spectral properties: the Qy absorption maximum
is 654 or 664 nm for the 2- or 3-formylchlorin, respectively. The synthetic formylchlorins provide initial
models for understanding the strong red absorption of native 2- or 3-formylchlorophylls (f and d).
Received (in Montpellier, France)
1st December 2013,
Accepted 10th February 2014
DOI: 10.1039/c3nj01508d
www.rsc.org/njc
of model chlorins that contain diverse auxochromes at the
3-position has proved incisive for probing the effects of auxo-
Introduction
Native chlorophylls are distinguished by the presence of auxo- chromes on spectral, electronic, and photophysical features.5–8
chromes at specific sites about the perimeter of the macrocycle. We sought similar access to synthetic 2-substituted chlorins for
Chlorophyll a and b both bear a vinyl group at the 3-position, fundamental comparisons of the effects of substituents at the
for example, whereas chlorophyll d contains a 3-formyl group 2- versus 3-positions.
(Chart 1).1 The location of auxochromes at the 3-position
The synthetic chemistry of chlorins has been a topic of
causes a hyperchromic and bathochromic effect on the long- widespread interest and has advanced considerably over the
wavelength absorption band (Qy band), which stems from a years.9–23 A de novo route that we have developed to gain access
transition that is polarized along the axis that bisects rings A to chlorins is shown in Scheme 1.24 Two halves, a Western half and
and C.2 The presence of a methyl group at the 2-position was an Eastern half, are joined in a convergent ring-forming process. The
long considered a universal feature of chlorophylls. However, Western half is a 2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin (or corre-
the recently discovered chlorophyll f contains a formyl group at sponding dihydrodipyrrin25) whereas the Eastern half is a 9-bromo-
the 2-position in addition to a 3-vinyl substituent.3,4 The synthesis 1-formyldipyrromethane. The chlorin bears a geminal dimethyl
group in the pyrroline ring thereby precluding adventitious
dehydrogenation leading to the porphyrin.
Department of Chemistry, North Carolina State University, Raleigh,
The synthesis of the Western half begins with a pyrrole-2-
NC 27695-8204, USA. E-mail: jlindsey@ncsu.edu
† Electronic supplementary information (ESI) available: Summary of NMR char- carboxaldehyde. A substituent can be incorporated at the
acterization of selected formyltetrahydrodipyrrins; X-ray data table for four
3-position of the chlorin by beginning with a 4-bromopyrrole-
compounds (1-BBu2, CCDC 974409; 1-Br8BBu2, CCDC 974410; 1-Br8F7BBu2, CCDC
2-carboxaldehyde (via the intermediacy of the 8-substituted
974411; 2-BBu2, CCDC 974412); display of the enantiomers of compound
1-Br8F7BBu2; exploratory results for decomplexation of 1-BR2; characterization
Western half).5 Pyrrole-2-carboxaldehyde readily undergoes
electrophilic bromination at the 4-position.26 Similarly, a
data for all new compounds. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c3nj01508d
13-substituted chlorin can be prepared by beginning with a
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 1717--1730 | 1717

View Article Online
Paper
NJC
Scheme 1 De novo route to 3,13-disubstituted chlorins.
As part of a program to improve tetrapyrrole synthetic metho-
dology, complexation aides were found to facilitate the isolation,
handling, and derivatization of acyldipyrromethanes, the precursors
Chart 1 Chlorin nomenclature and natural chlorophylls.
4-bromopyrrole-2-carboxaldehyde via the intermediacy of the to tetrapyrroles. The complexation aides include a dibutyltin complex
8-substituted Eastern half.5,27 By means of these and related of a 1,9-diacyldipyrromethane (A)42 and a dialkylboron complex of
approaches, all sites have been accessed (vide infra) to date with a 1-acyldipyrromethane (B)43 (Chart 2). The coordination complex
the sole exception of the chlorin 2-position (a 2-arylchlorin has been of each of these ligands was hydrophobic and could be easily
prepared28 but the route employed is not compatible with the purified by silica pad filtration and/or crystallization, whereas the
introduction of a 2-formyl group). The synthesis of a 2-bromo- uncomplexed species streaked upon chromatography and/or were
chlorin building block could begin with the corresponding poorly crystalline. Such dialkylboron complexation aides were
3-substituted pyrrole-2-carboxaldehyde, but the synthesis of applied to imidazolyl–dipyrromethanes (C and D),44 whereupon
such pyrroles is lengthy.29 During the course of this work, the isolated complex contained a covalent pyrrolic N–B bond and
Fukuda et al. reported a method for the directed lithiation at a dative imidazolyl N–B bond.
the 2-position of a 3-bromo-N-benzensulfonylpyrrole, which
Here, we sought to explore analogous complexation aides for
also could be employed as an early point of departure to access tetrahydrodipyrrins and dihydrodipyrrins, the precursors to hydro-
2-substituted pyrroles.30,31 Regardless, the motivation here was to porphyrins, wherein the bonding was expected to resemble that in
investigate complementary approaches for elaborating advanced the dialkylboron–imidazolyl–dipyrromethanes C and D. Tetrahydro-
precursors (i.e., hydrodipyrrins) to chlorins. While this work began dipyrrins typically are highly polar, streak on chromatographic
as an effort in pure synthesis, the subsequent discovery,3,32 struc- media, and do not readily crystallize. Moreover, the presence of
ture determination,4 and spectroscopic investigation33,34 of chloro- two heterocyclic rings with far different reactivity (pyrrole and pyrro-
phyll f; the growing appreciation of the rich ecological variety of line) can lead to unexpected reactions and synthetic difficulties.45
photosynthesis including use of the strong-red absorbing chloro- Dihydrodipyrrins are less polar but also less stable than tetrahydro-
phylls d and f;35–39 and consideration of the expanded (and possibly dipyrrins.24 Initially, our goal was to facilitate purification and
further expandable) spectral range of photosynthesis40,41 together handling of the tetrahydrodipyrrin, but in the course of our work
have heightened our focus on routes to chlorins that could we realized that boron complexation alters the usual selectivity of the
accommodate diverse substituents in ring A.
pyrrole upon electrophilic aromatic substitution.
1718 | New J. Chem., 2014, 38, 1717--1730
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
Table 1 Synthesis of dialkylboron complexes of tetrahydrodipyrrins
Entry
BR2-X
Product
R
R8
Yield (%)
1
2
3
BBu2-OTf
BMe2-Br
BBu2-OTf
1-BBu2
Bu
Me
Bu
H
H
Br
62
67
70
1-BMe2
1-Br8BBu2
afforded 1-BBu2 in pure form (62% yield; entry 1, Table 1). The
1-BBu2 complex is stable to routine handling. Crystals of 1-BBu2
suitable for X-ray analysis were obtained by slow evaporation of
a solution of Et2O–MeOH.
Reaction of 1 with dimethylboron bromide under nitrogen
at 0 1C afforded the corresponding dimethylboron complex
1-BMe2 in 67% yield (entry 2, Table 1). Compound 1-BMe2 was less
stable than 1-BBu2, decomposed on silica (thus purification was
performed by filtration through neutral alumina), and darkened
quickly when kept at room temperature. Because of instability,
compound 1-BMe2 was not fully characterized. Instability issues
with 1-BMe2 and problems with handling dimethylboron bromide
(highly pyrophoric, not available commercially as a solution) makes
application of 1-BMe2 less attractive than 1-BBu2. The dibutyl-
boron complex 1-Br8BBu2 was prepared in analogous fashion
from 8-bromotetrahydrodipyrrin5,51 1-Br8 in 70% yield (entry 3).
A crystal of 1-Br8BBu2 suitable for X-ray analysis was obtained
from CHCl3–hexanes by slow evaporation at 4 1C.
2. Dihydrodipyrrin–boron complexes. Treatment of p-tolyldi-
hydrodipyrrin 252 with BBu2OTf in the presence of Et3N in CH2Cl2
afforded dihydrodipyrrin complex 2-BBu2 in 87% yield (Scheme 2).
A crystal of 2-BBu2 suitable for X-ray analysis was obtained from
Et2O–MeOH by slow evaporation at 1 1C. The unsubstituted
dibutylboron complex 3-BBu2 was prepared in analogous fashion
from dihydrodipyrrin 353 in 27% yield.
Chart 2 Complexes of pyrrolic compounds.
In this paper, we report the investigation of dialkylboron
complexation of hydrodipyrrins. The dialkylboron unit masks both
the pyrrolic and pyrrolinic nitrogen atoms of the hydrodipyrrin. The
derivatization processes of interest include pyrrolic bromination and
formylation for potential synthetic elaboration of the corresponding
ring A of the chlorins. The dialkylboron unit directs substitution
chiefly to a pyrrolic b-position rather than the a-position (as occurs in
the unprotected pyrrole). One application of the dialkylboron com-
plexation method entails the de novo synthesis of 2-substituted free
base chlorins bearing bromo or formyl groups. An in-depth study of
the spectroscopic properties of the free base chlorins and metal
chelates will be described elsewhere. While our chief interests
concern spectroscopic properties, we note the work of Balaban
and Tamiaki, who have demonstrated that placement of carbonyl
groups at distinct locations enables control over the nature of
assemblies of tetrapyrrole macrocycles akin to chlorosome-like
architectures.19,46–49 Taken together, the results reported provide
an initial step toward partial mimics of chlorophyll f, and should
broaden the scope of synthetic chlorin chemistry.
II. Derivatization of hydrodipyrrin–dibutylboron complexes
1. Reconnaissance. Electrophilic aromatic substitution
of unsubstituted pyrrole proceeds first at the pyrrole a-positions.54
Results and discussion
I. Dialkylboron complexation of hydrodipyrrins
1. Tetrahydrodipyrrin–dialkylboron complexes. Tetrahydro-
dipyrrin 145 is a crucial building block in a rational synthesis of
chlorins.24,25,50 Reaction of 1 with dibutylboron triflate in CH2Cl2
containing triethylamine afforded the crude tetrahydrodipyrrin–
dialkylboron complex, which upon washing with saturated aqueous
NaHCO3, silica-pad filtration and recrystallization (aqueous ethanol)
Scheme 2 Synthesis of a dihydrodipyrrin–boron complex.
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 1717--1730 | 1719

View Article Online
Paper
NJC
Scheme 3 Pyrrolic a-bromination.
On the other hand, the regioselective bromination or acylation of
pyrroles at the b-positions presents a challenge.55 In general,
electrophilic aromatic substitution at the b-positions can be directed
(1) by an electron-withdrawing group at the a-position,5 (2) by a
bulky protecting group on the pyrrole nitrogen,56,57 or in some cases
(3) by rearrangement of the a-substituted pyrrole to a b-substituted
pyrrole.58–60 In accord with the expected reactivity of pyrrole, the
bromination of tetrahydrodipyrrin 1 proceeded at the 9-position53
(i.e., the free a-pyrrole position) to afford 1-Br9 (Scheme 3).
Here, we describe studies of electrophilic substitution of the
hydrodipyrrin–dialkylboron complexes, of which the tetra-
hydrodipyrrin species are the chief focus. The motivation for
developing chemistry for selective b-substitution stems from
the desire to introduce diverse substituents at the corre-
sponding positions of the pyrroles in the chlorin macrocycle,
in particular those in ring A.
2. Bromination or formylation. Bromination of tetrahydro-
dipyrrin 1-BBu2 with 1 molar equiv. of N-bromosuccinimide
(NBS) at ꢀ78 1C afforded three brominated products, namely
1-Br7BBu2, 1-Br7Br8BBu2 and 1-Br8BBu2 in the ratio 10 : 2 : 1 on
the basis of 1H NMR spectroscopy of the crude reaction mixture.
A small amount of unreacted starting material also was observed;
regardless, no a-pyrrole-substituted products were detected. The
main product, 1-Br7BBu2, was isolated in 53% yield upon recrys-
tallization three times from methanol (Scheme 4). (Note that
chromatography failed to separate 1-Br7BBu2 and 1-Br7Br8BBu2.)
The boron complex of bromohydrodipyrrin 1-Br7BBu2 is less stable
than that of the parent 1-BBu2.
Scheme 4 Electrophilic substitution of a dialkylboron–tetrahydrodipyrrin.
A Vilsmeier formylation of tetrahydrodipyrrin 1-BBu2 with
POCl3–DMF in CH2Cl2 afforded 7-formyltetrahydrodipyrrin
1-F7BBu2 as a major product with small amounts of regioisomers
1-F8BBu2 and 1-F9BBu2 (Scheme 4). Column chromatography
afforded pure 1-F7BBu2 in 70% yield. The position of the formyl
group in 1-F7BBu2 was established by 1H NMR spectroscopy
(see ESI†).
3. Formylation following bromination. The target 1-Br8F7BBu2
is a potentially valuable building block for chlorin synthesis,
given that the 8-position of a tetrahydrodipyrrin will become the
3-position of a chlorin. Accordingly, formylation of 1-Br8BBu2,
obtained by dialkylboron complexation of 1-Br8, was pursued.
Application of the same conditions (POCl3–DMF) employed for
1-BBu2, however, resulted in a mixture of products including
chloro/bromo exchange. Upon replacement of POCl3 with POBr3,61
several products were formed and isolated via chromatography for
characterization and yield determination (Scheme 5). The fractions
in order of elution include an unknown, isomer 1-Br8F9BBu2 Scheme 5 Formylation of 1-Br8BBu2.
1720 | New J. Chem., 2014, 38, 1717--1730
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
Scheme 6 Bromination of 1-F7BBu2.
Scheme 7 Bromination of a dihydrodipyrrin–boron complex.
chemistry,64 failed to form; (4) Pd-mediated coupling of bromo-
tetrahydrodipyrrin–dialkylboron complexes (e.g., 1-Br8BBu2) such
as carbonylation failed (as do such reactions in general with
uncomplexed hydrodipyrrins); and (5) treatment of 1-F7BBu2
with tert-butylamine gave the aldimine but ruthenium-mediated
attempts to install an alkyl group at the adjacent 8-position failed
(yet the reaction works well with arenes65). In summary, the
benefits of dialkylboron complexation, while significant, appear
limited at present to regioselective electrophilic substitution of
tetrahydrodipyrrins.
(9% yield), the desired compound 1-Br8F7BBu2 (46% yield), and
1-BBu2 (21% yield).
4. Bromination following formylation. Compound 1-Br8F7BBu2
was also synthesized via another route, in which 1-F7BBu2
served as the starting material. Thus, treatment of 1-F7BBu2
with NBS at ꢀ78 1C under argon afforded 1-Br8F7BBu2 in 69%
yield along with isomer 1-Br9F7BBu2 in 23% yield (Scheme 6).
A crystal of 1-Br8F7BBu2 suitable for X-ray analysis was obtained
from CH2Cl2–hexanes by slow evaporation at 4 1C. In summary,
the ability to gain access to the 8-bromo-7-formyl substitution
pattern appears quite attractive for eventual preparation of
chlorophyll f model compounds.
III. Characterization
5. Bromination
of
dihydrodipyrrin–boron
complexes.
1. NMR spectroscopy. The most pronounced changes in the
Bromination of dihydrodipyrrin 3-BBu2 with 1 molar equiv. of NBS 1H NMR spectrum upon complexation of tetrahydrodipyrrin 1 to
at ꢀ78 1C afforded three brominated products (Scheme 7), which give 1-BBu2 are as follows: (1) a downfield chemical shift of the
upon chromatography were identified as 3-Br7Br8BBu2 (28% yield), resonance of the 1-methyl group from 2.05 ppm to 2.41 ppm; and
3-Br8BBu2 (11% yield) and 3-Br7BBu2 (10% yield). A small amount of (2) a downfield chemical shift of the resonances of H2 (protons at
unreacted starting material also was observed; however, a-pyrrole- the pyrroline 2-position). For dihydrodipyrrin 2-BBu2 versus 2,
substituted products were not detected. The boron complexes of the the most significant chemical shift was observed for H5 (from
bromodihydrodipyrrin darkened and decomposed upon standing 5.97 ppm to 6.30 ppm). The resonances observed for protons in
overnight in CDCl3 (NMR tubes) at room temperature, reflecting the selected tetrahydrodipyrrins were assigned by NOESY and are
lesser stability versus the corresponding bromotetrahydrodipyrrin provided in the Experimental section.
complexes.
Each dialkylboron complex was examined by 11B NMR spectro-
6. Limitations of hydrodipyrrin–boron complexes. Dialkylboron scopy using the 11B standard, B(OH)3, at 19.8 ppm in DMF66 as a
complexation of the tetrahydrodipyrrin proved very beneficial in standard. Each dialkylboron complex exhibited a broad singlet in the
directing electrophilic substitution to the b- rather than a-pyrrolic range 0.89–2.72 ppm, to be compared with that of similar com-
positions. On the other hand, a number of other transformations pounds such as N-(9-borabicyclo[3.3.1]non-9-yl)pyrrole (59.9 ppm)67
were unsuccessful: (1) attempts to dehydrogenate tetrahydrodipyrrin and the 9-BBN complex of 1-acyldipyrromethanes (B13 ppm).43 The
1-BBu2 using a variety of reagents (DDQ, p-chloranil, SeO2, Pb(OAc)4– relative upfield shift of 1-BBu2 is characteristic for species in which
AcOH, CuO) to give dihydrodipyrrin 3-BBu2 failed (as does the boron is coordinated with an Nimino nitrogen.68
reaction with 1); (2) attempts to oxidize the 1-methyl group of
2. X-ray characterization. X-ray structural analysis was
tetrahydrodipyrrin 1-BBu2 with SeO2 to give the 1-formyl group performed of the dibutylboron complexes of three tetrahydro-
failed (yet the reaction succeeds with diverse dihydrodipyrrins62,63); dipyrrins (1-BBu2, 1-Br8BBu2, and 1-Br8F7BBu2) and dihydrodipyrrin
(3) the dibutylboron complex of a dihydrodipyrrin–acetal (analogue 2-BBu2 (Fig. 1). The tetrahydrodipyrrins each contain a stereogenic
of 1 bearing a 1,1-dimethoxymethyl group), used in bacteriochlorin center (C4) and are expected to form as racemic mixtures. In this
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 1717--1730 | 1721

View Article Online
Paper
NJC
Fig. 1 ORTEP drawing of (A) tetrahydrodipyrrin 1-BBu2, (B) tetrahydrodipyrrin 1-Br8BBu2, (C) dihydrodipyrrin 2-BBu2, and (D) tetrahydrodipyrrin
1-Br8F7BBu2. Ellipsoids are displayed at the 50% probability level and hydrogen atoms are omitted for clarity. The large spherical ellipsoids of 2-BBu2
result from high thermal motion.
regard, 1-Br8F7BBu2 crystallizes in a chiral space group Pna21, bond length in 1-BBu2 [1.570(3) Å], 1-Br8BBu2, [1.567(5) Å],
with the asymmetric unit (Z0 = 2) chosen to contain one 2-BBu2 [1.568(4) Å] and 1-Br8F7BBu2 [1.579(4) Å] is slightly
molecule of each enantiomer (see ESI†). The other materials shorter than for that of a 1-acyldipyrromethane [Chart 2B,
with stereogenic centers, 1-BBu2 and 1-Br8BBu2, crystallize in 1.5884(14) Å].43 The B–N (pyrrolinyl) bond length in 1-BBu2
the centrosymmetric space groups P21/n or P21/c respectively, [1.631(3) Å], 1-Br8BBu2 [1.637(4) Å], 1-Br8F7BBu2 [1.613(4) Å] and
containing both enantiomers in the unit cell. Electron-density 2-BBu2 [1.641(3) Å] is longer than that of the aforementioned
peaks in the difference map of 1-Br8F7BBu2 revealed disorder in B–N (pyrrolic) bond. The bromo and formyl group in 1-Br8F7BBu2
the position of Br on both of the molecules in the asymmetric unit are introduced via successive derivatization of 1-BBu2; thus, the
at the respective b-pyrrolic positions. Modeling this disorder single-crystal X-ray structure of 1-Br8F7BBu2 provides proof of the
favored (97 : 3) the bromine atom at the 8- versus 9-position of the regioselectivity of the electrophilic aromatic processes (bromination,
tetrahydrodipyrrin system. The 9-position is the pyrrole a-position, formylation) in the presence of the dibutylboron unit.
indicating a small amount of a-bromo substituted product
(1-Br9F7BBu2) in the isolated sample of 1-Br8F7BBu2.
IV. Decomplexation of dibutylboron–tetrahydrodipyrrins
A key difference between the two types of compounds is the The decomplexation of 1-BBu2 was examined under several
greater coplanarity of the pyrrole and pyrroline rings of dihydro- conditions, drawing on experience with conditions developed for
dipyrrin 2-BBu2 versus that of the tetrahydrodipyrrins due to the dialkylboron complexes of 1-acyldipyrromethanes (e.g., Chart 2B).43
unsaturated versus saturated C4–C5 bond, respectively. Regardless, The exploratory studies are summarized in the ESI† (Table S4).
the butyl chains attached to the boron center are thrust above and The use of 1-pentanol at reflux43 caused decomplexation but the
below the ligand plane in each case, as expected. The B–N (pyrrolic) liberated 1 did not precipitate from hexanes, which prompted
1722 | New J. Chem., 2014, 38, 1717--1730
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
Scheme 8 Decomplexation of b-pyrrolic substituted dibutylboron–
tetrahydrodipyrrins.
examination of other conditions. Refluxing solutions containing
phenoxide anion, hydrazine monohydrate, or KOH were success-
ful with 1-BBu2 but upon application to the formyl compound
1-F7BBu2 gave only starting material. Attempts to use KOH
(50 equiv.) or TBAF also did not afford 1-F7. The milder base
K2CO3 in methanol led to the desired compound, but with a
large amount of starting material. K3PO4 afforded better solubility
in methanol and increased the yield to 60% yield for 1-F7. The
same conditions with 1-Br8F7BBu2 or 1-Br7BBu2 gave the free
tetrahydrodipyrrin 1-Br8F7 or 1-Br7 in 63% or 66% yield, respec-
tively (Scheme 8).
Scheme 9 Synthesis of formylchlorins.
V. Isomeric formylchlorins
1. Synthesis. Two isomeric formylchlorins were prepared
in a continuation of our studies of the effects of auxochromes
Treatment of the bromochlorin FbC-Br2 or FbC-Br3 with
on the spectral properties of chlorins. Prior theoretical studies Bu3SnH and a stoichiometric amount of Pd(PPh3)4 in toluene/
have ‘‘walked the formyl group around the macrocycle’’ but no DMF (1 : 1) at 70 1C under an atmosphere of CO gave the corres-
experimental studies have yet made available the 2-formylchlorin ponding 2-formylchlorin FbC-F2 or 3-formylchlorin FbC-F3 in 32%
and 3-formylchlorin (a 3-formyl-10-mesitylchlorin has been pre- or 43% yield, respectively. Each target chlorin was characterized by
pared previously5). Formylchlorins can be prepared by Pd-mediated absorption spectroscopy, 1H NMR spectroscopy, 13C NMR spectro-
carbonylation of the corresponding bromochlorins.69 Access to the scopy and high-resolution mass spectrometry.
2-bromochlorin was achieved by bromination of the dibutylboron-
2. Absorption spectral properties. The absorption spectra
complexed Western half (1-BBu2), whereas a 3-bromochlorin was of formylchlorins FbC-F2 and FbC-F3 in toluene are shown in
prepared by installation of the bromo group in the earliest pre- Fig. 2, along with that of the benchmark chlorin70 FbC that
cursor, pyrrole-2-carboxaldehyde. Thus, the reaction of Eastern half lacks any b-pyrrole substituents (Scheme 9, R2 = R3 = H). Each
450 and Western half 1-Br7 or 1-Br8 was employed to synthesize chlorin exhibits an intense B (Soret) band and a characteristic
2-bromochlorin FbC-Br2 or 3-bromochlorin FbC-Br3, respectively, as strong Qy band. The spectra are normalized at the B (Soret)
shown in Scheme 9. Compound 1-Br7 was obtained by bromination band for facile comparison of the relative intensity of the long-
of 1-BBu2 followed by decomplexation and chromatographic wavelength Qy band.
purification, whereas 1-Br8 is a known compound5,51 obtained
The unsubstituted chlorin FbC exhibits B and Qy absorption
from 4-bromopyrrole-2-carboxaldehyde. The chlorin-forming at 389 and 634 nm, respectively. The presence of a formyl group in
reaction was carried out under standard conditions of acid- ring A causes a pronounced bathochromic shift of both B and Qy
catalyzed condensation ( p-TsOHꢁH2O in MeOH–CH2Cl2 under bands, the magnitude of which depends on the position. While
argon for 50 min) followed by zinc(II)-mediated oxidative cycli- the position of both B and Qy bands determines the extent of light
zation [Zn(OAc)2, 2,2,6,6-tetramethylpiperidine (TMPi), and harvesting, the position of the Qy band is of particular importance
AgOTf in CH3CN at reflux exposed to air for 22 h]. The resulting as this sets an upper limit on the energy of the first excited singlet
zinc chlorins were then demetalated upon treatment with state, from which photochemical processes emanate. Thus, FbC-F2
trifluoroacetic acid (TFA). This route provided access to the or FbC-F3 exhibits Qy absorption maximum at 654 or 664 nm (Dl =
free base 2-bromochlorin or 3-bromochlorin in yield of 5% or 20 or 30 nm relative to FbC), respectively. A parallel bathochromic
14%, respectively. The yields, while low, are typical of those for shift is exhibited by the B band, which appears at 404 or 416 nm
sparsely substituted chlorins.50
for FbC-F2 or FbC-F3, respectively.
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 1717--1730 | 1723

View Article Online
Paper
NJC
Fig. 3 Preferred site(s) of electrophilic substitution in hydrodipyrrin–
boron complexes.
Fig. 2 Absorption spectra in toluene at room temperature (normalized at
the B bands) of FbC (black), FbC-F2 (blue) and FbC-F3 (red).
rise to the chlorin 2-position. The role of steric versus electronic
factors that underpin the unusual substitution pattern in the
tetrahydrodipyrrin–dialkylboron complex remains unknown.
Regardless, in combination with literature data, a trend has emerged
for electrophilic substitution of increasingly unsaturated substrates,
as shown in Fig. 3. Substitution of the tetrahydrodipyrrin–
dialkylboron complex proceeds chiefly at the 7-position (adjacent
to the alkyl substituent); for the dihydrodipyrrin–dialkylboron
complex, reaction proceeds equivalently at the 7- and 8-positions;
and for the dipyrrin–difluoroboron complex (i.e., a BODIPY
dye), bromination (Br2),71 chlorination (NCS),72 or formylation
(Vilsmeier, 80 1C)73 proceeds selectively at the 8-position. The
steric effects of the 5-aryl group in these substitution processes
remain unknown.
The availability of the 2-formyl and 3-formylchlorins lacking
any other substituents enables fundamental studies to assess
the origin of the spectral and photophysical properties of the
more highly substituted natural chlorophylls.40,74 The de novo
route complements semisynthesis approaches that begin with
natural chlorophylls.75 The access to 2-substituted chlorins now
completes our circumambulation of the ring, as access to
the 3,5,76 5,24,25,50 7,69,76,77 8,77 10,24,25,50 12,27,28 13,2,5,78
15,70,76,78,79 17,70,80 18,80 and 2069,79 positions has already
been achieved, as has installation of the isocyclic ring2,81 (and
6-membered imide analogues78 thereof) characteristic of the
native chlorophyll structures. More generally, the availability of
2-substituted chlorins provides an initial approach toward
sparsely substituted chlorophyll f analogues.
Table 2 Absorption spectral properties of chlorinsa
Chlorins
lB (fwhm) in (nm)
lQ (fwhm) in (nm)
B/Qy ratio
y
FbC
389 (33)
404 (34)
416 (38)
634 (9)
654 (11)
664 (14)
2.4
2
1.8
FbC-F2
FbC-F3
a
In toluene at room temperature.
The ratio of the intensities of the B and Qy bands provides a
measure of the relative absorption, and is particularly conve-
nient given the difficulty of accurate determination of molar
absorption coefficients with small samples. In this regard, the
B/Qy band intensity ratio decreases slightly along the series FbC
(2.4), FbC-F2 (2.0), and FbC-F3 (1.8). Thus, the formyl group
introduces a bathochromic and relative hyperchromic shift on
the Qy band, with the effect larger at the 3- versus 2-position.
Such shifts are accompanied by a broadening of both the B and
Qy bands, as measured by the full-width-at-half-maximum (fwhm).
The fwhm increases along the series FbC, FbC-F2, and FbC-F3
from 33 to 38 nm for the B band and 9 to 14 nm for the Qy band.
The spectral data are listed in Table 2. The large fwhm (38 nm) of
the B band of FbC-F3 stems from a short-wavelength shoulder of
significant intensity, as seen in Fig. 2.
Conclusions and outlook
Directed routes to stable hydroporphyrins rely extensively on
hydrodipyrrin chemistry, a domain of chemistry where much
methodology development remains to be done. In general, the
Experimental section
I. General procedures
synthetic methods available for manipulating hydrodipyrrins 1H (400 MHz) and 13C (100 MHz) NMR spectra were recorded in
are incommensurate with the architectural challenges and CDCl3 at room temperature unless noted otherwise. 11B NMR
scientific opportunities presented by the target macrocycles. spectroscopy (160 MHz) was performed at room temperature
The work described herein has established a new route to using a boron-free NMR tube, CDCl3 as solvent, and B(OH)3 in
2-substituted chlorins. The route relies on the formation of a DMF as external standard (referenced to 19.8 ppm).66 Absorption
dibutylboron complex of a tetrahydrodipyrrin, the Western half spectra were collected in toluene at room temperature. Melting
precursor to the chlorin. The introduction of dialkylboron unit points are uncorrected. Silica gel (40 mm average particle size) was
directs electrophilic aromatic substitution (bromination, formyla- used for column chromatography. Compounds 1,45 1-Br8,5,51 2,52
tion) chiefly to the b-pyrrolic 7-position, which ultimately gives 3,53 and 450 were prepared as described in the literature.
1724 | New J. Chem., 2014, 38, 1717--1730
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
II. Preparations
0.72 mmol) in CH2Cl2 (0.5 mL) was treated with dibutylboron
triflate (0.48 mL, 1 M in CH2Cl2, 0.48 mmol) under argon at room
temperature. The reaction mixture was stirred for 1 h under
argon. The reaction mixture was quenched with water. The
organic phase was washed (brine), dried (Na2SO4), concentrated,
and chromatographed [silica, hexanes/CH2Cl2 (1 : 1)] to afford
a light yellow solid (20 mg, 27%): mp 98–100 1C; 1H NMR
d 0.60–0.72 (m, 2H), 0.73–0.78 (m, 10H), 0.84–0.92 (m, 2H),
1.11–1.20 (m, 4H), 1.25 (s, 6H), 2.44 (s, 3H), 2.77 (s, 2H), 6.07
(s, 1H), 6.09–6.13 (m, 1H), 6.16–6.20 (m, 1H), 6.78–6.82 (m, 1H);
13C NMR d 14.3, 18.9, 25.9, 26.3, 27.9, 29.1, 29.8, 37.2, 54.5, 107.5,
108.5, 109.6, 125.5, 128.3, 147.4, 175.0; ESI-MS obsd 313.2720,
calcd 313.2813 [(M + H)+, M = C20H33BN2].
10-(Dibutylboryl)-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin
(1-BBu2). A solution of 1 (380 mg, 2.00 mmol) in CH2Cl2 (4.0 mL)
was treated with triethylamine (1.0 mL) and dibutylboron triflate
(4.00 mL of 1 M solution in CH2Cl2, 2 mmol). The reaction
mixture was stirred at room temperature. After 1 h, CH2Cl2 was
added. TLC analysis [silica, hexanes/CH2Cl2 (2: 1)] showed the
presence of a yellow, highly fluorescent, non-polar product (trace
amount, Rf = 0.57) in addition to the title compound (Rf = 0.50).
The yellow impurity could not be removed by chromatography or
crystallization, but was removed upon washing the organic
phase three times with aqueous NaHCO3. The organic phase
was concentrated. The resulting oil was filtered through a pad of
silica (CH2Cl2). The filtrate was concentrated. Crystallization
from hot EtOH–water afforded pale yellow crystals that gave a
single spot upon TLC analysis (389 mg, 62%): mp 135–136 1C;
11B d 0.98; 1H NMR d 0.42–0.55 (m, 2H), 0.62–0.66 (m, 2H),
0.79–0.82 (m, 6H), 1.11 (s, 3H), 1.14–1.19 (m, 4H) 1.21 (s, 3H),
1.20–1.22 (m, 4H), 2.38–2.39 (m, 3H), 2.60–2.65 (m, 1H),
2.77–2.81 (m, 1H) 2.82–2.85 (m, 2H), 3.82–3.86 (m, 1H),
5.90–5.91 (m, 1H), 6.09–6.10 (m, 1H), 6.66–6.67 (m, 1H); 13C
NMR d 14.29, 14.38, 19.1, 23.0, 23.5, 25.2, 26.2, 26.6, 26.7, 28.1,
28.4, 38.8, 56.1, 80.0, 102.8, 106.1, 121.1, 130.1, 180.4; ESI-MS
obsd 315.2970, calcd 315.2966 [(M + H)+, M = C20H35BN2].
10-(Dimethylboryl)-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin
(1-BMe2). A solution of 1 (0.190 g, 1.00 mmol) in CH2Cl2
(4.0 mL) was treated with triethylamine (0.5 mL) and dimethyl-
boron bromide (0.195 mL, 2.00 mmol) at 0 1C. After 5 min, the
cooling bath was removed and the mixture was stirred at room
temperature for 1 h. Then, the mixture was concentrated. The
resulting material was filtered through neutral alumina (CH2Cl2)
to afford an off-white solid (0.154 g, 67%). Due to instability, the
characterization of the title compound was incomplete: 1H NMR
d 0.00 (s, 3H), 0.20 (s, 3H), 1.03 (s, 3H), 1.21 (s, 3H), 2.39–2.40
(m, 3H), 2.58–2.63 (m, 1H), 2.73–2.78 (m, 1H), 2.82–2.85 (m, 1H),
2.87–2.91 (m, 1H), 3.96–4.00 (m, 1H), 5.90–5.91 (m, 1H),
6.12–6.13 (m, 1H), 6.70–6.71 (m, 1H); 13C NMR 19.4, 23.3, 25.5,
26.3, 38.7, 56.2, 78.8, 103.5, 106.8, 129.2.
7,8-Dibromo-10-(dibutylboryl)-2,3-dihydro-1,3,3-trimethyl-
dipyrrin (3-Br7Br8BBu2).
A solution of 3-BBu2 (18 mg,
0.058 mmol) in THF (1.2 mL) was chilled in a dry ice–acetone
bath for 10 min under argon. Then, the solution was treated
with one portion of NBS (10.3 mg, 0.058 mmol). After stirring
for 1 h at ꢀ78 1C, hexanes was added, and the mixture was
allowed to warm by removal of the dry ice–acetone bath. Water
was added when the internal reaction temperature reached
0 1C. The organic phase was washed (water), dried (Na2SO4),
concentrated and chromatographed [silica, CH2Cl2/hexanes
(1 : 4)]. Four bands were observed in the following order of
elution: unreacted starting material, 3-Br7BBu2 (2.0 mg, 10%),
3-Br8BBu2 (2.4 mg, 11%), and the title compound (7.6 mg,
28%). The title compound was a yellow solid with fluorescence
under long-wavelength UV illumination. Each of the isolated
compounds is somewhat unstable, hence the assignments are
provisional on the basis of limited characterization data. Data
for the title compound: 1H NMR d 0.60–0.72 (m, 2H), 0.73–0.78
(m, 10H), 0.84–0.92 (m, 2H), 1.11–1.20 (m, 4H), 1.25 (s, 6H),
2.42 (s, 3H), 2.80 (s, 2H), 6.05 (s, 1H), 6.74 (s, 1H); ESI-MS obsd
468.1055, calcd 468.1056 [(M + H)+, M = C20H31BBr2N2].
Data for 8-bromo-10-(dibutylboryl)-2,3-dihydro-1,3,3-trimethyl-
dipyrrin (3-Br8BBu2): 1H NMR d 0.60–0.72 (m, 2H), 0.73–0.78
(m, 10H), 0.84–0.92 (m, 2H), 1.11–1.20 (m, 4H), 1.25 (s, 6H),
2.44 (s, 3H), 2.80 (s, 2H), 6.10 (s, 1H), 6.12 (d, J = 2.8 Hz, 1H),
6.71 (d, J = 2.8 Hz, 1H).
10-(Dibutylboryl)-2,3-dihydro-1,3,3-trimethyl-7-(4-methylphenyl)-
dipyrrin (2-BBu2). A solution of 2 (0.100 g, 0.359 mmol) and
triethylamine (0.18 mL, 1.3 mmol) in CH2Cl2 (5.1 mL) was treated
with dibutylboron triflate (0.72 mL, 1 M in CH2Cl2, 0.72 mmol)
under argon at room temperature. The reaction mixture was stirred
for 1 h under argon. The reaction mixture was quenched with
water. The organic phase was dried (Na2SO4), concentrated, and
chromatographed [silica, hexanes/CH2Cl2 (1 : 1)] to afford a light
Data for 7-bromo-10-(dibutylboryl)-2,3-dihydro-1,3,3-trimethyl-
dipyrrin (3-Br7BBu2): 1H NMR d 0.60–0.72 (m, 2H), 0.73–0.78
(m, 10H), 0.84–0.92 (m, 2H), 1.11–1.20 (m, 4H), 1.25 (s, 6H), 2.42
(s, 3H), 2.80 (s, 2H), 6.05 (s, 1H), 6.12 (s, 1H), 6.74 (s, 1H); ESI-MS
obsd 390.1959, calcd 390.1951 [(M + H)+, M = C20H32BBrN2].
7-Bromo-10-(dibutylboryl)-2,3,4,5-tetrahydro-1,3,3-trimethyl-
dipyrrin (1-Br7BBu2). A solution of 1-BBu2 (200 mg, 0.636 mmol)
in THF (12.8 mL) at ꢀ78 1C under argon was treated with
NBS (112 mg, 0.636 mmol). The reaction mixture was
stirred for 1 h at ꢀ78 1C under argon. Hexanes was added.
Water was added when the internal reaction temperature
reached 0 1C. The organic phase was separated, dried (Na2SO4),
and concentrated. Recrystallization three times from methanol
afforded the title compound (100 mg, 40%). The mother liquor
was collected and recrystallized three times from methanol to
afford an additional 32 mg, giving a total yield of 53% (132 mg):
mp 105–107 1C; 11B d 1.19; 1H NMR d 0.35–0.55 (m, 2H),
1
yellow solid (0.13 g, 87%): mp 87–88 1C; H NMR d 0.70–0.89 (m,
12H), 0.96–1.04 (m, 2H), 1.17–1.22 (m, 7H), 1.27 (s, 3H), 2.35 (s, 3H),
2.42 (s, 3H), 2.74 (s, 3H), 6.32–6.34 (m, 1H), 6.83–6.84 (m, 1H), 7.20
(d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H); 13C NMR d 8.9, 14.4, 19.1,
21.3, 26.3, 28.0, 29.2, 37.6, 46.8, 54.6, 108.7, 124.0, 125.3, 128.1,
129.3, 134.5, 135.0, 147.9, 174.7; ESI-MS obsd 402.3320, calcd
402.3315 [(M + H)+, M = C27H39BN2].
10-(Dibutylboryl)-2,3-dihydro-1,3,3-trimethyldipyrrin (3-BBu2).
A solution of 3 (45 mg, 0.24 mmol) and triethylamine (0.10 mL,
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 1717--1730 | 1725

View Article Online
Paper
NJC
0.58–0.85 (m, 8H), 0.89–1.27 (m, 8H), 1.03 (s, 3H), 1.24 (s, 3H), 1.08 (s, 3H), 1.10–1.18 (m, 2H), 1.19–1.26 (m, 2H), 1.25 (s, 3H),
3.38 (d, J = 1.9 Hz, 3H), 2.59–2.69 (m, 2H), 2.78–2.93 (m, 2H), 2.41 (d, J = 5.0 Hz, 3H), 2.70–2.74 (m, 1H), 2.79–2.87 (m, 3H),
3.77–3.83 (m, 1H), 6.12 (d, J = 2.8 Hz, 1H), 6.61 (d, J = 2.8 Hz, 3.79–3.81 (m, 1H), 6.36–6.38 (m, 1H), 7.29 (s, 1H), 9.68 (s, 1H);
1H); 13C NMR d 14.33, 14.39, 19.1, 23.0, 23.3, 23.6, 26.3, 26.47, 13C NMR d 14.4, 19.2, 23.5, 25.1, 26.1, 26.43, 26.52, 27.8, 28.1,
26.62, 27.9, 28.2, 38.8, 56.1, 79.3, 90.5, 108.6, 120.7, 127.3, 39.0, 56.1, 79.5, 102.9, 126.6, 132.7, 133.6, 181.8, 185.7; ESI-MS
181.1; ESI-MS obsd 392.2111, calcd 392.2108 [(M + H)+, M = obsd 343.2924, calcd 343.2919 [(M + H)+, M = C21H35BN2O].
C
20H34BBrN2]. The same procedure at the 50 mg (0.16 mmol)
Data for 10-(dibutylboryl)-9-formyl-2,3,4,5-tetrahydro-1,3,3-
scale with chromatography [silica, hexanes/CH2Cl2 (4 : 1)] trimethyldipyrrin (1-F9BBu2): TLC Rf = 0.65 [silica, hexanes/
afforded the title product (28 mg, 45%) containing 10% of ethyl acetate (1 : 1)]; mp 94–95 1C; 11B d 2.44; 1H NMR
dibromo impurity (1-Br7Br8BBu2). Also, no increase in selectivity d 0.44–0.55 (m, 2H), 0.58–0.83 (m, 10H), 0.87–0.99 (m, 2H),
was achieved upon treatment of a 5-fold less concentrated 1.08 (s, 3H), 1.10–1.18 (m, 2H), 1.19–1.26 (m, 2H), 1.26 (s, 3H),
solution of 1-BBu2 (10 mM) with NBS solution (20 mM) via 2.46 (d, J = 5.0 Hz, 3H), 2.70–2.91 (m, 3H), 2.95 (dd, J = 3.6 Hz,
cannula (dropwise) over 1 h.
J = 15.4 Hz, 1H), 3.93–3.97 (m, 1H), 6.02 (d, J = 3.9 Hz, 1H), 7.14
8-Bromo-10-(dibutylboryl)-2,3,4,5-tetrahydro-1,3,3-trimethyl- (d, J = 3.9 Hz, 1H), 9.81 (s, 1H); 13C NMR d 14.3, 19.5, 23.7,
dipyrrin (1-Br8BBu2). A solution of 1-Br8 (600 mg, 2.23 mmol) 26.23, 26.34, 26.43, 27.2, 28.54, 28.64, 29.9, 38.0, 56.4, 78.2,
in anhydrous CH2Cl2 (15 mL) was treated with triethylamine 107.9, 120.9, 136.4, 140.3, 180.9, 181.6; ESI-MS obsd 343.2925,
(1.1 mL, 8.00 mmol) and dibutylboron triflate (4.5 mL, 1 M in calcd 343.2919 [(M + H)+, M = C21H35BN2O].
CH2Cl2, 0.45 mmol). The reaction mixture was stirred at room
8-Bromo-10-(dibutylboryl)-7-formyl-2,3,4,5-tetrahydro-1,3,3-
temperature for 1 h. Water was added. The organic extract was trimethyldipyrrin (1-Br8F7BBu2). The route here entailed
washed (brine), dried (Na2SO4), concentrated and chromato- formylation following bromination. A solution of 1-Br8BBu2
graphed [silica, hexanes/CH2Cl2 (2 : 1)] to afford white crystals (100 mg, 0.255 mmol) and DMF (0.078 mL) in CH2Cl2 (2.5 mL)
(612 mg, 70%): mp 118–120 1C (dec.); 11B d 0.97; 1H NMR d was treated with POBr3 (80.2 mg, 0.280 mmol) at 0 1C under
0.39–0.54 (m, 2H), 0.55–0.91 (m, 10H), 1.01 (s, 3H), 1.07–1.18 argon. After stirring for 2.5 h at 0 1C, a 2 M aqueous solution of
(m, 4H), 1.19–1.30 (m, 2H), 1.22 (s, 3H), 2.38 (d, J = 2.2 Hz, 3H), NaOH (10 mL) was added at 0 1C. The reaction mixture was
2.64 (dd, J = 18 Hz, J = 1.5 Hz, 1H), 2.76–2.83 (m, 3H), 3.78–3.82 vigorously stirred for 20 min at 0 1C. The organic phase
(m, 1H), 5.89 (d, J = 1.8 Hz, 1H), 6.58 (d, J = 1.8 Hz, 1H); 13C NMR was washed (water, brine), dried (Na2SO4), concentrated and
d 14.0, 14.1, 18.8, 23.2, 24.7, 25.9, 26.23, 26.29, 27.6, 27.9, 38.5, 55.7, chromatographed [silica, hexanes/ethyl acetate (2 : 1)] to give
79.1, 93.1, 105.3, 120.2, 130.3, 180.8; ESI-MS obsd 392.2097, calcd the title compound as a dark red solid. Data for 1-Br8F7BBu2:
392.2108 [(M + H)+, M = C20H34BBrN2].
mp 90–92 1C; 11B d 0.98; 1H NMR d 0.41–0.46 (m, 2H),
10-(Dibutylboryl)-7-formyl-2,3,4,5-tetrahydro-1,3,3-trimethyl- 0.57–0.84 (m, 10H), 0.87–0.99 (m, 2H), 1.07 (s, 3H), 1.10–1.18
dipyrrin (1-F7BBu2). A solution of 1-BBu2 (568 mg, 1.81 mmol) (m, 2H), 1.19–1.24 (m, 2H), 1.26 (s, 3H), 2.41 (d, J = 1.8 Hz, 3H),
and DMF (1.00 mL, 13.0 mmol) in CH2Cl2 (13.9 mL) was 2.66–2.88 (m, 3H), 3.68–3.84 (m, 2H), 6.57 (s, 1H), 9.76 (s, 1H);
treated with POCl3 (0.185 mL, 1.99 mmol) at 0 1C under 13C NMR d 14.31, 14.32, 19.2, 22.9, 23.6, 24.1, 26.28, 26.31,
argon. After stirring for 3 h at 0 1C, the reaction mixture 26.36, 27.9, 28.1, 39.0, 56.0, 77.6, 99.5, 117.0, 122.0, 138.5,
was treated with 2 M aqueous NaOH (10 mL) at 0 1C. The 182.5, 186.6; ESI-MS obsd 421.2032, calcd 421.2024 [(M + H)+,
reaction mixture was vigorously stirred for 20 min at 0 1C. M = C21H34BBrN2O].
The organic phase was washed (water, brine), dried (Na2SO4),
Data for 8-bromo-10-(dibutylboryl)-9-formyl-2,3,4,5-tetrahydro-
concentrated and chromatographed [silica, hexanes/ethyl 1,3,3-trimethyldipyrrin (1-Br8F9BBu2): 11B d 1.45; 1H NMR
acetate (1 : 1)]. Three products were isolated in the following d 0.41–0.46 (m, 2H), 0.57–0.84 (m, 10H), 0.87–0.99 (m, 2H),
order: 1-F9BBu2 (yellow solid, 9 mg, 1%), 1-F8BBu2 (yellow solid, 1.07 (s, 3H), 1.10–1.18 (m, 2H), 1.19–1.24 (m, 2H), 1.26 (s, 3H),
9 mg, 1%), and the title compound 1-F7BBu2 (yellow solid, 2.41 (d, J = 2.0 Hz, 3H), 2.56–2.86 (m, 3H), 3.74–3.82 (m, 2H),
435 mg, 70% yield). (Note that thorough removal of DMF prior 7.33 (s, 1H), 9.73 (s, 1H); 13C NMR d 14.19, 14.23, 19.1, 22.3,
to chromatography is crucial for the separation.) Data for 23.6, 24.5, 26.03, 26.07, 26.2, 27.6, 27.8, 38.9, 56.0, 78.7, 122.7,
1-F7BBu2: TLC Rf = 0.40 [silica, hexanes/ethyl acetate (1 : 1)]; 129.7 130.8, 182.4, 185.3; ESI-MS obsd 421.2020, calcd 421.2024
mp 114–116 1C; 11B d 0.89; 1H NMR d 0.44–0.55 (m, 2H), [(M + H)+, M = C21H34BBrN2O].
0.58–0.83 (m, 10H), 0.87–0.99 (m, 2H), 1.08 (s, 3H), 1.10–1.18
(m, 2H), 1.19–1.26 (m, 2H), 1.27 (s, 3H), 2.41 (d, J = 5.0 Hz, 3H), following formylation.
The title compound was also synthesized by bromination
solution of 1-F7BBu2 (200 mg,
A
2.69–2.87 (m, 3H), 3.57–3.63 (m, 1H), 3.81–3.86 (m, 1H), 6.53 0.583 mmol) in THF (11.6 mL) was chilled in an acetone–dry
(d, J = 2.7 Hz, 1H), 6.61 (d, J = 2.7 Hz, 1H), 9.77 (s, 1H); 13C NMR d ice bath for 10 min under argon. Then the solution was treated
13.46, 13.50, 18.3, 22.2, 22.8, 23.2, 25.46, 25.52, 25.6, 27.1, 27.4, with one portion of NBS (104 mg, 0.583 mmol). After stirring for
38.1, 55.3, 77.2, 109.7, 120.0, 121.9, 137.9, 181.2, 184.8; ESI-MS 1 h at ꢀ78 1C, hexanes was added. Water was added when the
obsd 343.2945, calcd 343.2952 [(M + H)+, M = C21H35BN2O].
internal reaction temperature reached 0 1C. The organic phase
Data for 10-(dibutylboryl)-8-formyl-2,3,4,5-tetrahydro-1,3,3- was washed (water), dried (Na2SO4), concentrated and chroma-
trimethyldipyrrin (1-F8BBu2): TLC Rf = 0.50 [silica, hexanes/ tographed [silica, hexanes/ethyl acetate (2 : 1)] to give the title
ethyl acetate (1 : 1)]; mp 104.5–106.5 1C; 11B d 1.09; 1H NMR compound as a dark red solid (168 mg, 69%) as well as isomer
d 0.44–0.55 (m, 2H), 0.58–0.83 (m, 10H), 0.87–0.99 (m, 2H), 1-Br9F7BBu2 (56 mg, 23%). Data for 1-Br8F7BBu2 are the same
1726 | New J. Chem., 2014, 38, 1717--1730
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
as above. Data for 9-bromo-10-(dibutylboryl)-7-formyl-2,3,4,5-
2-Bromo-17,18-dihydro-18,18-dimethylporphyrin (FbC-Br2).
tetrahydro-1,3,3-trimethyldipyrrin (1-Br9F7BBu2): mp 159–161 1C; Following a general procedure,24 a solution of 1-Br7 (300 mg,
1
11B d 2.72; H NMR (300 MHz) d 0.41–0.46 (m, 2H), 0.57–0.83 1.12 mmol) and 4 (282 mg, 1.12 mmol) in anhydrous CH2Cl2
(m, 10H), 0.87–0.99 (m, 2H), 1.08 (s, 3H), 1.10–1.18 (m, 2H), (26.4 mL) was treated with a solution of p-TsOHꢁH2O (1.05 g,
1.19–1.26 (m, 2H), 1.27 (s, 3H), 2.41 (d, J = 1.8 Hz, 3H), 2.65–2.89 5.54 mmol) in anhydrous methanol (5.28 mL) under argon.
(m, 3H), 3.69 (dd, J = 16.2 and 3.6 Hz, 1H), 3.88–4.00 (m, 1H), The reaction mixture immediately turned red. The mixture was
6.59 (s, 1H), 9.70 (s, 1H); 13C NMR d 14.2, 14.3, 19.3, 23.3, 23.5, stirred for 50 min under argon, then treated with 2,2,6,6-
23.7, 25.2, 26.0, 26.2, 27.4, 28.0, 28.5, 37.9, 56.3, 77.5, 104.1, tetramethylpiperidine (2.03 mL, 11.9 mmol) and concentrated
114.7, 121.3, 139.8, 181.7, 184.9; ESI-MS obsd 421.2038, calcd to dryness. The resulting brown solid was suspended in aceto-
421.2024 [(M + H)+, M = C21H34BBrN2O].
nitrile (110 mL) followed by the successive addition of 2,2,6,6-
7-Formyl-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin
(1-F7). tetramethylpiperidine (5.28 mL, 30.8 mmol), Zn(OAc)2 (3.04 g,
A sample of 1-F7BBu2 (343 mg, 1.00 mmol) in CH3OH (40 mL) 16.6 mmol) and AgOTf (854 mg, 3.32 mmol). The resulting
was treated with K3PO4 (10.6 g, 50.0 mmol) and refluxed for suspension was refluxed for 22 h exposed to air. The crude
20 h. Upon cooling to room temperature, the mixture was mixture was filtered through a silica pad with CH2Cl2. The
washed with water and brine. The organic layer was dried filtrate was concentrated and dissolved in anhydrous CH2Cl2
(NaSO4) and concentrated. The crude product was chromato- (66 mL). TFA (880 mL) was added dropwise to the resulting
graphed (silica, ethyl acetate) to afford a light yellow oil mixture. After 5 min, saturated aqueous NaHCO3 was added
(130 mg, 60%) and recovered starting material (21 mg, 6%). slowly. The organic layer was extracted, dried (NaSO4) and
Data for the title compound: 1H NMR (300 MHz) d 0.98 (s, 3H), concentrated. The crude product was chromatographed [silica,
1.16 (s, 3H), 2.05 (d, J = 1.6 Hz, 3H), 2.34 (AB, 2J = 16.8 Hz, 1H), CH2Cl2/hexanes (1 : 2)] to afford a green solid (23 mg, 5%):
2.42 (AB, 2J = 16.8 Hz, 1H), 2.61 (ABX, 2J = 15.6 Hz, 3J = 12.0 Hz, 1H NMR d ꢀ2.48 (br s, 2H), 2.10 (s, 6H), 4.63 (s, 2H),
1H), 3.41 (ABX, 2J = 15.6 Hz, 3J = 2.8 Hz, 1H), 3.63–3.69 (m, 1H), 8.94 (d, J = 4.4 Hz, 1H), 9.06–9.07 (m, 3H), 9.10 (s, 1H), 9.25
6.54–6.57 (m, 1H), 6.66–6.69 (m, 1H), 9.90 (s, 1H), 10.73–10.89 (d, J = 4.4 Hz, 1H), 9.29 (s, 1H), 9.80 (s, 1H), 9.85 (s, 1H);
(br s, 1H); 13C NMR d 20.7, 23.1, 26.0, 27.2, 42.3, 54.5, 79.4, 13C NMR d 31.6, 47.0, 52.2, 92.8, 97.3, 105.0, 106.52, 106.62,
109.0, 118.2, 121.6, 141.2, 175.6, 186.0; ESI-MS obsd 219.1500, 124.4, 128.1, 128.6, 132.8, 133.2; ESI-MS obsd 419.0874, calcd
calcd 219.1492 [(M + H)+, M = C13H18N2O].
419.0866 [(M + H)+, M = C22H19BrN4]; labs 391, 641 nm.
8-Bromo-7-formyl-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin
3-Bromo-17,18-dihydro-18,18-dimethylporphyrin (FbC-Br3).
(1-Br8F7). A sample of 1-Br8F7BBu2 (120 mg, 0.286 mmol) in Following a general procedure,24 a solution of 1-Br8 (534 mg,
CH3OH (11 mL) was treated with K3PO4 (3.00 g, 14.3 mmol) and 1.98 mmol) and 4 (498 mg, 1.98 mmol) in anhydrous CH2Cl2
refluxed for 20 h. Upon cooling to room temperature, the (52 mL) was treated with a solution of p-TsOHꢁH2O (1.88 g,
mixture was washed with water and brine. The organic layer 9.90 mmol) in anhydrous methanol (13 mL) under argon. The
was dried (NaSO4) and concentrated. The crude product was reaction mixture immediately turned red. The mixture was
chromatographed (silica, ethyl acetate) to afford a yellow oil stirred for 50 min under argon, then treated with 2,2,6,6-
(54 mg, 63%) and recovered starting material (7 mg, 6%). Data for tetramethylpiperidine (2.5 mL, 15 mmol) and concentrated to
the title compound: 1H NMR (300 MHz) d 0.96 (s, 3H), 1.18 (s, 3H), dryness. The resulting brown solid was suspended in aceto-
2.03 (d, J = 1.6 Hz, 3H), 2.35 (AB, 2J = 12.6 Hz, 1H), 2.40 nitrile (200 mL) followed by the successive addition of 2,2,6,6-
2
2
3
(AB, J = 12.6 Hz, 1H), 2.54 (ABX, J = 11.8 Hz, J = 9.0 Hz, 1H), tetramethylpiperidine (6.6 mL, 40 mmol), Zn(OAc)2 (5.45 g,
3.54 (ABX, 2J = 11.8, 3J = 2.6 Hz, 1H), 3.65–3.68 (m, 1H), 6.59 (s, 1H), 29.4 mmol) and AgOTf (1.53 g, 5.94 mmol). The resulting
9.89 (s, 1H), 11.28–11.50 (br s, 1H); 13C NMR d 20.4, 23.0, 26.3, 26.9, suspension was refluxed for 22 h exposed to air. The crude
42.2, 54.4, 79.0, 99.4, 117.4, 122.0, 140.4, 175.8, 187.2; ESI-MS obsd mixture was filtered through a silica pad with CH2Cl2. The
297.0600, calcd 297.0597 [(M + H)+, M = C13H17BrN2O].
filtrate was concentrated and dissolved in anhydrous CH2Cl2
8-Bromo-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin (1-Br7). (100 mL). TFA (1.5 mL) was added dropwise to the resulting
A sample of 1-Br7BBu2 (250 mg, 0.633 mmol) in CH3OH mixture. After 5 min, saturated aqueous NaHCO3 was added
(25.0 mL) was treated with K3PO4 (6.67 g, 31.3 mmol) and slowly. The organic layer was extracted, dried (NaSO4) and
refluxed for 14 h. Upon cooling to room temperature, the concentrated. The crude product was chromatographed [silica,
mixture was washed with water and brine. The organic layer CH2Cl2/hexanes (1 : 2)] to afford a green solid (116 mg, 14%):
was dried (NaSO4) and concentrated. The crude product was 1H NMR d ꢀ2.49 (s, 2H), 2.03 (s, 6H), 4.60 (s, 2H), 8.84 (s, 1H),
chromatographed (silica, ethyl acetate) to afford a red oil 8.90 (d, J = 4.0 Hz, 1H), 9.00 (s, 1H), 9.01–9.03 (m, 2H), 9.08
(112 mg, 66%): 1H NMR (300 MHz) d 0.96 (s, 3H), 1.14 (d, J = 4.0 Hz, 1H), 9.19 (d, J = 4.8 Hz, 1H), 9.78 (s, 1H), 9.92
2
(s, 3H), 2.04 (d, J = 1.8 Hz, 3H), 2.331 (AB, J = 16.8 Hz, 1H), (s, 1H); 13C NMR d 31.4, 46.7, 52.0, 94.2, 97.0, 105.0, 106.6,
2.335 (AB, 2J = 16.8 Hz, 1H), 2.41 (ABX, 2J = 16.0 Hz, 3J = 11.4 Hz, 124.2, 128.6, 132.7, 133.2; ESI-MS obsd 419.0875, calcd
1H), 2.84 (ABX, 2J = 16.0 Hz, 3J = 4.0 Hz, 1H), 3.56–3.62 (m, 1H), 419.0866 [(M + H)+, M = C22H19BrN4]; labs 391, 640 nm.
6.10 (t, J = 3.0 Hz, 1H), 6.60 (t, J = 3.0 Hz, 1H), 10.00–10.26
2-Formyl-17,18-dihydro-18,18-dimethylporphyrin (FbC-F2).
(br s, 1H); 13C NMR (75 MHz) d 20.4, 22.8, 26.0, 27.0, 42.0, 54.3, Following a procedure for reductive carbonylation,69 a mixture
79.5, 93.8, 109.9, 116.5, 129.0, 175.1; ESI-MS obsd 269.0652, of FbC-Br2 (30.0 mg, 0.0715 mmol) and Pd(PPh3)4 (82.6 mg,
calcd 269.0648 [(M + H)+, M = C12H17BrN2].
0.0715 mmol) was dried under vacuum for 1 h. The reaction
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 1717--1730 | 1727

View Article Online
Paper
NJC
flask was filled with CO gas and anhydrous toluene/DMF 11B NMR spectra were collected at the National Institutes of
[3.6 mL, (1: 1)]. CO gas was bubbled through the stirred reaction Environmental and Health Sciences in Research Triangle Park
mixture for 2 h at 70 1C. The reaction mixture then was treated with the assistance of Dr Xiaoyan Sun. Mass spectra were
with Bu3SnH (20.0 mL, 0.0715 mmol) and stirred for 10 min. obtained at the Mass Spectrometry Laboratory for Biotechnology
The reaction mixture was then cooled to room temperature, at North Carolina State University. Partial funding for the facility
concentrated and subjected to column chromatography [silica, was obtained from the North Carolina Biotechnology Center and
CH2Cl2/hexanes (1: 1)] to afford a green solid (8.5 mg, 32%): the National Science Foundation.
1H NMR d ꢀ1.58 (br s, 2H), 2.05 (s, 6H), 4.54 (s, 2H), 8.32
(d, J = 5.0 Hz, 1H), 8.85–8.87 (m, 2H), 8.97 (d, J = 4.0 Hz, 1H), 9.08
(d, J = 4.0 Hz, 1H), 9.53 (s, 1H), 9.54 (s, 1H), 9.69 (s, 1H), 9.76
References
(s, 1H), 11.25 (s, 1H); 13C NMR d 31.6, 46.4, 52.7, 94.5, 97.1, 105.6,
110.6, 126.2, 129.9, 131.4, 132.6, 134.7, 137.6, 141.9, 151.5, 155.1,
167.0, 176.6, 188.6; ESI-MS obsd 369.1706, calcd 369.1710
[(M + H)+, M = C23H20N4O]; labs 404, 654 nm.
1 H. Scheer, in Chlorophylls and Bacteriochlorophylls. Biochem-
istry, Biophysics, Functions and Applications, ed. B. Grimm,
R. J. Porra, W. Ru¨diger and H. Scheer, Springer, Dordrecht,
The Netherlands, 2006, pp. 1–26.
2 O. Mass, M. Taniguchi, M. Ptaszek, J. W. Springer,
K. M. Faries, J. R. Diers, D. F. Bocian, D. Holten and
J. S. Lindsey, New J. Chem., 2011, 35, 76–88.
3 M. Chen, M. Schliep, R. D. Willows, Z.-L. Cai, B. A. Neilan
and H. Scheer, Science, 2010, 329, 1318–1319.
4 R. D. Willows, Y. Li, H. Scheer and M. Chen, Org. Lett., 2013,
15, 1588–1590.
5 J. K. Laha, C. Muthiah, M. Taniguchi, B. E. McDowell,
M. Ptaszek and J. S. Lindsey, J. Org. Chem., 2006, 71,
4092–4102. J. Org. Chem., 2009, 74, 5122, Erratum.
6 H. L. Kee, C. Kirmaier, Q. Tang, J. R. Diers, C. Muthiah,
M. Taniguchi, J. K. Laha, M. Ptaszek, J. S. Lindsey,
D. F. Bocian and D. Holten, Photochem. Photobiol., 2007,
83, 1110–1124.
7 H. L. Kee, C. Kirmaier, Q. Tang, J. R. Diers, C. Muthiah,
M. Taniguchi, J. K. Laha, M. Ptaszek, J. S. Lindsey,
D. F. Bocian and D. Holten, Photochem. Photobiol., 2007,
83, 1125–1143.
3-Formyl-17,18-dihydro-18,18-dimethylporphyrin (FbC-F3).
Following a procedure for reductive carbonylation,69 a mixture
of FbC-Br3 (0.100 g, 0.238 mmol) and Pd(PPh3)4 (0.275 g,
0.238 mmol) was dried under vacuum for 1 h. The reaction
flask was filled with CO gas and anhydrous toluene/DMF
[12.0 mL, (1 : 1)]. CO gas was bubbled through the stirred
reaction mixture for 2 h at 70 1C. The reaction mixture then
was treated with Bu3SnH (63.7 mL, 0.238 mmol) and stirred for
10 min. The reaction mixture was then cooled to room tempera-
ture, concentrated and subjected to column chromatography
[silica, CH2Cl2/hexanes (1: 1)] to afford a brown solid (38.0 mg,
43%): 1H NMR d ꢀ2.16 (br s, 2H), 2.04 (s, 6H), 4.60 (s, 2H), 8.91
(d, J = 4.0 Hz, 1H), 8.93–8.95 (m, 2H), 9.00 (s, 1H), 9.08
(d, J = 4.0 Hz, 1H), 9.15 (d, J = 4 Hz, 1H), 9.35 (s, 1H), 9.65
(s, 1H), 10.52 (s, 1H), 11.4 (s, 1H); 13C NMR d 31.6, 46.2, 52.7, 96.9,
98.0, 105.1, 106.9, 126.0, 126.2, 129.3, 133.3, 135.3, 136.4, 137.6,
140.7, 153.2, 155.0, 165.3, 173.7, 188.9; ESI-MS obsd 369.1718,
calcd 369.1710 [(M + H)+, M = C23H20N4O]; labs 416, 664 nm.
III. X-ray structural determinations
8 J. W. Springer, K. M. Faries, H. L. Kee, J. R. Diers, C. Muthiah,
O. Mass, C. Kirmaier, J. S. Lindsey, D. F. Bocian and
D. Holten, Photochem. Photobiol., 2012, 88, 651–674.
9 W. Flitsch, Adv. Heterocycl. Chem., 1988, 43, 73–126.
10 K. M. Smith, in Chlorophylls, ed. H. Scheer, CRC Press, Boca
Raton, FL, USA, 1991, pp. 115–143.
All X-ray measurements were made on a Bruker-Nonius X8 Apex2
CCD system. The frame integration was performed using SAINT+ or
SAINT.82 The structures 1-BBu2 and 2-BBu2 were solved using direct
methods from SIR9283 and refined using the NRCVAX84 crystallo-
graphic suite. The structures of 1-Br8BBu2 and 1-Br8F7BBu2 were
solved by direct methods using the SHELX201385 package. The
calculated structure factors included corrections for polarization,
and an absorption correction using SADABS.86 The structure was
refined using the SHELXL program from the SHELX201385 package,
and graphic plots were produced using the OLEX287 crystallographic
package. Additional positions for disordered atoms were found in
subsequent difference maps during multiple rounds of refinement.
The hydrogen-atom positions were placed at idealized positions and
were allowed to ride on the parent atom with isotropic displacement
parameters of 1.2 or 1.5 times the parent.
11 P. H. Hynninen, in Chlorophylls, ed. H. Scheer, CRC Press,
Boca Raton, FL, USA, 1991, pp. 145–209.
¨
12 F.-P. Montforts, B. Gerlach and F. Hoper, Chem. Rev., 1994,
94, 327–347.
13 F.-P. Montforts and M. Glasenapp-Breiling, Prog. Heterocycl.
Chem., 1998, 10, 1–24.
14 M. G. H. Vicente, in The Porphyrin Handbook, ed. K. M. Kadish,
K. M. Smith and R. Guilard, Academic Press, San Diego, CA,
2000, vol. 1, pp. 149–199.
15 L. Jaquinod, in The Porphyrin Handbook, ed. K. M. Kadish,
K. M. Smith and R. Guilard, Academic Press, San Diego, CA,
2000, vol. 1, pp. 201–237.
16 R. K. Pandey and G. Zheng, in The Porphyrin Handbook,
ed. K. M. Kadish, K. M. Smith and R. Guilard, Academic
Press, San Diego, CA, 2000, vol. 6, pp. 157–230.
Acknowledgements
This work was supported by a grant from the Chemical Sciences,
Geosciences and Biosciences Division, Office of Basic Energy 17 F.-P. Montforts and M. Glasenapp-Breiling, Fortschr. Chem.
Sciences, of the U. S. Department of Energy (DE-FG02-96ER14632). Org. Naturst., 2002, 84, 1–51.
1728 | New J. Chem., 2014, 38, 1717--1730
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
18 V. Y. Pavlov and G. V. Ponomarev, Chem. Heterocycl. Compd., 45 M. Ptaszek, J. Bhaumik, H.-J. Kim, M. Taniguchi and
2004, 40, 393–425. J. S. Lindsey, Org. Process Res. Dev., 2005, 9, 651–659.
19 T. S. Balaban, H. Tamiaki and A. R. Holzwarth, Top. Curr. 46 T. S. Balaban, M. Linke-Schaetzel, A. D. Bhise, N. Vanthuyne
Chem., 2005, 258, 1–38. and C. Roussel, Eur. J. Org. Chem., 2004, 3919–3930.
20 M. O. Senge, A. Wiehe and C. Ryppa, in Chlorophylls and 47 T. S. Balaban, Acc. Chem. Res., 2005, 38, 612–623.
¨
Bacteriochlorophylls. Biochemistry, Biophysics, Functions and 48 T. Jochum, C. M. Reddy, A. Eichhofer, G. Buth,
Applications, ed. B. Grimm, R. J. Porra, W. Ru¨diger and
H. Scheer, Springer, Dordrecht, The Netherlands, 2006,
pp. 27–37.
J. Szmytkowski, H. Kalt, D. Moss and T. S. Balaban, Proc.
Natl. Acad. Sci. U. S. A., 2008, 105, 12736–12741.
49 T. S. Balaban, A. D. Bhise, G. Bringmann, J. Bu¨rck,
¨ ¨
C. Chappaz-Gillot, A. Eichhofer, D. Fenske, D. C. G. Gotz,
21 S. Fox and R. W. Boyle, Tetrahedron, 2006, 62, 10039–10054.
22 M. Galezowski and D. T. Gryko, Curr. Org. Chem., 2007, 11,
1310–1338.
¨
¨
M. Knauer, T. Mizoguchi, D. Mossinger, H. Rosner,
C. Roussel, M. Schraut, H. Tamiaki and N. Vanthuyne,
J. Am. Chem. Soc., 2009, 131, 14480–14492.
23 A. M. G. Silva and J. A. S. Cavaleiro, in Progress in Hetero-
cyclic Chemistry, ed. G. W. Gribble and J. A. Joule, Elsevier, 50 M. Ptaszek, B. E. McDowell, M. Taniguchi, H.-J. Kim and
Amsterdam, 2008, ch. 2, vol. 19, pp. 44–69. J. S. Lindsey, Tetrahedron, 2007, 63, 3826–3839.
24 M. Taniguchi, D. Ra, G. Mo, T. Balasubramanian and 51 M. Krayer, T. Balasubramanian, C. Ruzie, M. Ptaszek,
´
J. S. Lindsey, J. Org. Chem., 2001, 66, 7342–7354.
25 J.-P. Strachan, D. F. O’Shea, T. Balasubramanian and
J. S. Lindsey, J. Org. Chem., 2000, 65, 3160–3172.
D. L. Cramer, M. Taniguchi and J. S. Lindsey, J. Porphyrins
Phthalocyanines, 2009, 13, 1098–1110.
52 H.-J. Kim and J. S. Lindsey, WO Pat., 2006089122, 2007.
26 H. J. Anderson and S.-F. Lee, Can. J. Chem., 1965, 43, 53 H.-J. Kim, D. K. Dogutan, M. Ptaszek and J. S. Lindsey,
409–414. Tetrahedron, 2007, 63, 37–55.
27 O. Mass, M. Ptaszek, M. Taniguchi, J. R. Diers, H. L. Kee, 54 A. H. Jackson, in Pyrroles. Part One. The Synthesis and the
D. F. Bocian, D. Holten and J. S. Lindsey, J. Org. Chem., 2009,
74, 5276–5289.
Physical and Chemical Aspects of the Pyrrole Ring, ed.
R. A. Jones, John Wiley & Sons, New York, 1990, pp. 295–303.
28 T. Balasubramanian, J.-P. Strachan, P. D. Boyle and 55 C. Schmuck and D. Rupprecht, Synthesis, 2007, 3095–3110.
J. S. Lindsey, J. Org. Chem., 2000, 65, 7919–7929.
29 L. Ghosez, C. Franc, F. Denonne, C. Cuisinier and
R. Touillaux, Can. J. Chem., 2001, 79, 1827–1839.
30 T. Fukuda, T. Ohta, E.-I. Sudo and M. Iwao, Org. Lett., 2010,
12, 2734–2737.
56 J. M. Muchowski and D. R. Solas, Tetrahedron Lett., 1983, 24,
3455–3456.
57 B. L. Bray, P. H. Mathies, R. Naef, D. R. Solas, T. T. Tidwell,
D. R. Artis and J. M. Muchowski, J. Org. Chem., 1990, 55,
6317–6328.
31 T. Fukuda and M. Iwao, Heterocycles, 2012, 86, 1261–1273.
32 M. Chen, Y. Li, D. Birch and R. D. Willows, FEBS Lett., 2012,
586, 3249–3254.
33 Y. Li, N. Scales, R. E. Blankenship, R. D. Willows and
M. Chen, Biochim. Biophys. Acta, 2012, 1817, 1292–1298.
34 Y. Li, Z.-L. Cai and M. Chen, J. Phys. Chem. B, 2013, 117,
11309–11317.
35 S. Ohashi, H. Miyashita, N. Okada, T. Iemura, T. Watanabe
and M. Kobayashi, Photosynth. Res., 2008, 98, 141–149.
36 B. Krau¨tler, Angew. Chem., Int. Ed., 2011, 50, 2439–2441.
37 A. M. Wood, J. Phycol., 2012, 48, 1317–1319.
58 M. Kakushima, P. Hamel, R. Frenette and J. Rokach, J. Org.
Chem., 1983, 48, 3214–3219.
59 R. Settambolo, R. Lazzaroni, T. Messeri, M. Mazzetti and
P. Salvadori, J. Org. Chem., 1993, 58, 7899–7902.
60 C. Zonta, F. Fabris and O. De Lucchi, Org. Lett., 2005, 7,
1003–1006.
61 K. R. Reddy, J. Jiang, M. Krayer, M. A. Harris, J. W. Springer,
E. Yang, J. Jiao, D. M. Niedzwiedzki, D. Pandithavidana,
P. S. Parkes-Loach, C. Kirmaier, P. A. Loach, D. F. Bocian,
D. Holten and J. S. Lindsey, Chem. Sci., 2013, 4,
2036–2053.
¨
38 A. W. D. Larkum, M. Chen, Y. Li, M. Schliep, E. Trampe, 62 P. A. Jacobi, S. Lanz, I. Ghosh, S. H. Leung, F. Lower and
J. West, A. Salih and M. Ku¨hl, J. Phycol., 2012, 48, 1320–1327. D. Pippin, Org. Lett., 2001, 3, 831–834.
39 M. Schliep, G. Cavigliasso, R. G. Quinnell, R. Stranger and 63 K. R. Reddy, E. Lubian, M. P. Pavan, H.-J. Kim, E. Yang,
A. W. D. Larkum, Plant, Cell Environ., 2013, 36, 521–527.
40 M. Chen and R. E. Blankenship, Trends Plant Sci., 2011, 16,
427–431.
41 M. Chen and H. Scheer, J. Porphyrins Phthalocyanines, 2013,
17, 1–15.
D. Holten and J. S. Lindsey, New J. Chem., 2013, 37,
1157–1173.
64 H.-J. Kim and J. S. Lindsey, J. Org. Chem., 2005, 70,
5475–5486.
65 F. Kakiuchi, M. Yamauchi, N. Chatani and S. Murai, Chem.
Lett., 1996, 111–112.
42 S.-I. Tamaru, L. Yu, W. J. Youngblood, K. Muthukumaran,
M. Taniguchi and J. S. Lindsey, J. Org. Chem., 2004, 69, 66 M. J. S. Dewar and R. Jones, J. Am. Chem. Soc., 1967, 89,
765–777. 2408–2410.
43 K. Muthukumaran, M. Ptaszek, B. Noll, W. R. Scheidt and 67 B. Wrackmeyer and B. Schwarze, J. Organomet. Chem., 1997,
J. S. Lindsey, J. Org. Chem., 2004, 69, 5354–5364. 534, 207–211.
44 J. Bhaumik, Z. Yao, K. E. Borbas, M. Taniguchi and 68 B. Wrackmeyer, Annu. Rep. NMR Spectrosc., 1988, 20,
J. S. Lindsey, J. Org. Chem., 2006, 71, 8807–8817. 61–203.
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 1717--1730 | 1729

View Article Online
Paper
NJC
69 C. Muthiah, D. Lahaye, M. Taniguchi, M. Ptaszek and 80 M. Taniguchi, H.-J. Kim, D. Ra, J. K. Schwartz, C. Kirmaier,
J. S. Lindsey, J. Org. Chem., 2009, 74, 3237–3247.
70 M. Taniguchi, M. Ptaszek, B. E. McDowell and J. S. Lindsey,
Tetrahedron, 2007, 63, 3840–3849.
71 L. Jiao, W. Pang, J. Zhou, Y. Wei, X. Mu, G. Bai and E. Hao,
J. Org. Chem., 2011, 76, 9988–9996.
E. Hindin, J. R. Diers, S. Prathapan, D. F. Bocian, D. Holten
and J. S. Lindsey, J. Org. Chem., 2002, 67, 7329–7342.
81 J. K. Laha, C. Muthiah, M. Taniguchi and J. S. Lindsey,
J. Org. Chem., 2006, 71, 7049–7052.
82 (a) Bruker-Nonius, SAINT+ version 7.07B, Bruker-Nonius,
Madison, WI 53711, USA, 2004; (b) Bruker-Nonius, SAINT
version 2009.9, Bruker-Nonius, Madison, WI 53711, USA,
2009; (c) A. Bruker-Nonius, SAINT version 7.78A, Bruker-
Nonius, Madison, WI 53711, USA, 2009; (d) A. Bruker-
Nonius, SAINT version 8.32B, Bruker-Nonius, Madison, WI
53711, USA, 2013.
72 G. Duran-Sampedro, A. R. Agarrabeitia, I. Garcia-Moreno,
˜
A. Costela, J. Banuelos, T. Arbeloa, I. Lopez Arbeloa,
J. L. Chiara and M. J. Ortiz, Eur. J. Org. Chem., 2012,
6335–6350.
73 C. Yu, L. Jiao, H. Yin, J. Zhou, W. Pang, Y. Wu, Z. Wang,
G. Yang and E. Hao, Eur. J. Org. Chem., 2011, 5460–5468.
74 W. M. Manning and H. H. Strain, J. Biol. Chem., 1943, 151, 83 A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi,
1–19.
M. C. Burla, G. Polidori and M. Camalli, J. Appl. Crystallogr.,
1994, 27, 435.
75 H. Tamiaki and M. Kunieda, in Handbook of Porphyrin
Science, ed. K. M. Kadish, K. M. Smith and R. Guilard, World 84 E. J. Gabe, Y. Le Page, J.-P. Charland, F. L. Lee and
Scientific Co., Singapore, 2011, ch. 51, vol. 11, pp. 223–290. P. S. White, J. Appl. Crystallogr., 1989, 22, 384–387.
76 O. Mass, D. R. Pandithavidana, M. Ptaszek, K. Santiago, 85 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr.,
J. W. Springer, J. Jiao, Q. Tang, C. Kirmaier, D. F. Bocian, 2008, 64, 112–122.
D. Holten and J. S. Lindsey, New J. Chem., 2011, 35, 86 (a) A. Bruker-Nonius, SADABS version 2.10, Bruker-Nonius,
2671–2690.
Madison, WI 53711, USA, 2004; (b) A. Bruker-Nonius, SADABS
version 2009.9, Bruker-Nonius, Madison, WI 53711, USA, 2009;
(c) A. Bruker-Nonius, SADABS version 2008/1, Bruker-Nonius,
Madison, WI 53711, USA, 2008; (d) A. Bruker-Nonius, SADABS
version 2012/1, Bruker-Nonius, Madison, WI 53711, USA, 2012.
77 C. Muthiah, M. Ptaszek, T. M. Nguyen, K. M. Flack and
J. S. Lindsey, J. Org. Chem., 2007, 72, 7736–7749.
78 M. Ptaszek, D. Lahaye, M. Krayer, C. Muthiah and
J. S. Lindsey, J. Org. Chem., 2010, 75, 1659–1673.
79 M. Taniguchi, M. N. Kim, D. Ra and J. S. Lindsey, J. Org. 87 O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard
Chem., 2005, 70, 275–285.
and H. Puschmann, J. Appl. Crystallogr., 2009, 42, 339–341.
1730 | New J. Chem., 2014, 38, 1717--1730
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014