Regioselective 15-bromination and functionalization of a stable synthetic bacteriochlorin

Article abstract of DOI:10.1021/jo070785s

(Chemical Equation Presented) 5-Methoxy-8,8,18,18-tetramethyl-2,12-di-p- tolylbacteriochlorin (MeO-BC) undergoes regioselective electrophilic bromination with NBS to give the 15-bromo analogue (MeO-BC-Br¹⁵) in 85% yield. By contrast, the bacter

Full text of DOI:10.1021/jo070785s

Regioselective 15-Bromination and Functionalization of a Stable
Synthetic Bacteriochlorin
Dazhong Fan, Masahiko Taniguchi, and Jonathan S. Lindsey*
Department of Chemistry, North Carolina State UniVersity, Raleigh, North Carolina 27695-8204
jlindsey@ncsu.edu
ReceiVed April 15, 2007
5-Methoxy-8,8,18,18-tetramethyl-2,12-di-p-tolylbacteriochlorin (MeO-BC) undergoes regioselective elec-
trophilic bromination with NBS to give the 15-bromo analogue (MeO-BC-Br15) in 85% yield. By contrast,
the bacteriochlorin lacking the 5-methoxy group (8,8,18,18-tetramethyl-2,12-di-p-tolylbacteriochlorin,
H-BC) gives a mixture of two monobromo- and two dibromobacteriochlorins. Deuterium exchange of
both bacteriochlorins (H-BC and MeO-BC) in acidic media (TFA-d) occurs preferentially at the â-pyrrole
positions (3, 13) > unhindered meso-positions (5, 15 for H-BC; 15 for MeO-BC) > hindered meso-
positions (10, 20). The 15-bromo-5-methoxybacteriochlorin MeO-BC-Br15 was subjected to three types
of Pd-mediated coupling reactions (Suzuki, Sonogashira, Hartwig-Buchwald) to give six bacteriochlorins
bearing functional groups at the 15-position (49% to 85% yield). The groups include 4-(tert-
butoxycarbonylmethoxy)phenyl, 4-pyridyl, 3,5-diformylphenyl, phenylethynyl, TIPS-ethynyl, and N-
benzamido. The presence of the 15-ethynyl moiety shifts the position of the long-wavelength Qy band
from 732 nm to ∼753 nm. The ability to introduce a range of groups at a specific site enables synthetic
bacteriochlorins to be tailored for a variety of applications.
Introduction
rearrangement.4 Routes to bacteriochlorins that lack this stabiliz-
ing structural motif include the derivatization of naturally
occurring chlorophylls, manipulation of naturally occurring
bacteriochlorophylls, and reduction of synthetic porphyrins or
chlorins.5
We recently developed a concise rational synthesis of stable
bacteriochlorins.1 The bacteriochlorins are stable to adventitious
oxidation by virtue of the presence of a geminal dimethyl group
in each of the two reduced, pyrroline rings. The synthetic
bacteriochlorins exhibit the characteristic absorption features of
naturally occurring bacteriochlorins, namely strong absorption
in the near-UV and the near-IR spectral regions. To our
knowledge, the only other bacteriochlorins bearing geminal-
dialkyl groups in both pyrroline rings include members of the
tolyporphin family of natural products,2 of which tolyporphin
A has been the target of a lengthy total synthesis by Kishi,3
and synthetic bacteriochlorins derived from â-alkyl-substituted
porphyrins by vicinal dihydroxylation followed by pinacol
The access to stable bacteriochlorins holds promise for a
number of applications where strong absorption in the near-IR
(2) (a) Prinsep, M. R.; Caplan, F. R.; Moore, R. E.; Patterson, G. M. L.;
Smith, C. D. J. Am. Chem. Soc. 1992, 114, 385-387. (b) Prinsep, M. R.;
Patterson, G. M. L.; Larsen, L. K.; Smith, C. D. Tetrahedron 1995, 51,
10523-10530. (c) Prinsep, M. R.; Patterson, G. M. L.; Larsen, L. K.; Smith,
C. D. J. Nat. Prod. 1998, 61, 1133-1136.
(3) (a) Minehan, T. G.; Kishi, Y. Tetrahedron Lett. 1997, 38, 6811-
6814. (b) Minehan, T. G.; Kishi, Y. Tetrahedron Lett. 1997, 38, 6815-
6818. (c) Minehan, T. G.; Kishi, Y. Angew. Chem., Int. Ed. 1999, 38, 923-
925. (d) Minehan, T. G.; Cook-Blumberg, L.; Kishi, Y.; Prinsep, M. R.;
Moore, R. E. Angew. Chem., Int. Ed. 1999, 38, 926-928. (e) Wang, W.;
Kishi, Y. Org. Lett. 1999, 1, 1129-1132.
(1) Kim, H.-J.; Lindsey, J. S. J. Org. Chem. 2005, 70, 5475-5486.
10.1021/jo070785s CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/13/2007
5350
J. Org. Chem. 2007, 72, 5350-5357

Functionalization of a Stable Synthetic Bacteriochlorin
SCHEME 1
spectral region is essential. In photomedical applications,
photosensitizers and optical imaging agents are desired that
strongly absorb near-IR light, which affords deep penetration
in soft tissue.6 In diagnostics applications, compounds with
sharp, wavelength-tunable absorption/emission bands in the
near-IR would be useful as fluorescent markers.7 In artificial
photosynthesis, molecular absorbers that capture the large
fraction of sunlight that is in the near-IR are essential contribu-
tors to the overall solar-conversion efficiency.8 All such
applications share a common design requirement for the ability
to tailor the substituents at the perimeter of the macrocycle,
such as introducing groups to modify solubility or enable
conjugation to biological targeting agents, a surface, or another
chromophore.
The few bacteriochlorins that have been used in photomedi-
cine generally are naturally occurring bacteriochlorins them-
selves (e.g., tolyporphins)9 or derivatives therefrom, particularly
from bacteriochlorophyll a.10 Relatively few synthetic modifica-
tions have been carried out with naturally occurring bacterio-
chlorins such as bacteriochlorophyll a, owing to the presence
of a full complement of â-pyrrolic substituents and limited
stability of the bacteriochlorin toward oxidation and other side
reactions.11 In this paper, we report the regioselective bromi-
nation of a bacteriochlorin and use of the resulting bromo-
bacteriochlorin as a versatile building block in the synthesis of
a variety of tailored bacteriochlorins.
Results and Discussion
halogenation. The bromination or iodination was performed
according to literature procedures that have been employed for
porphyrins or chlorins.12-15 The bromination of H-BC (5-
substituent ) H) with NBS (1 equiv) in CHCl3 (1% pyridine)
was examined. The reaction was complete at room temperature
1. Halogenation of Bacteriochlorins. Two synthetic bacte-
riochlorins (H-BC, MeO-BC)1 were available for studies of
(4) (a) Barkigia, K. M.; Fajer, J.; Chang, C. K.; Young, R. J. Am. Chem.
Soc. 1984, 106, 6457-6459. (b) Pandey, R. K.; Isaac, M.; MacDonald, I.;
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1
within 10 min. H NMR spectroscopy of the crude reaction
mixture showed the presence of the following components:
H-BC-Br3 (32%), H-BC-Br5 (21%), H-BC-Br3Br13 (11%),
H-BC-Br5Br13 (4%), and unreacted H-BC (32%) (Scheme 1).
The crude reaction mixture was separated into two fractions:
the first fraction consisted of a mixture of the two dibromo-
bacteriochlorins, whereas the second fraction consisted of the
two monobromobacteriochlorins. Further purification was un-
successful; however, NOESY spectra of each fraction gave a
clear view of the substitution pattern (see the Supporting
Information for detailed 1H NMR spectra and NOESY experi-
ments).
There are three possible monobromobacteriochlorins (and
nine possible dibromobacteriochlorins) given the presence of
three distinct sites for bromination: (i) the â (3 or 13)-position
flanking each p-tolyl group, (ii) the unhindered meso (5 or 15)-
position, and (iii) the sterically hindered meso (10 or 20)-
position. The fewer number of products stems from bromination
solely at the â-position and unhindered meso-position, with no
bromination of the sterically hindered meso-position. The
â-positions were more than twice as reactive as the unhindered
meso-positions, as measured by the total bromination at the
(7) Perfetto, S. P.; Chattopadhyay, P. K.; Roederer, M. Nat. ReV.
Immunol. 2004, 4, 648-655.
(8) Hasselman, G. M.; Watson, D. F.; Stromberg, J. S.; Bocian, D. F.;
Holten, D.; Lindsey, J. S.; Meyer, G. J. J. Phys. Chem. B 2006, 110, 25430-
25440.
(9) Morlie`re, P.; Mazie`re, J.-C.; Santus, R.; Smith, C. D.; Prinsep, M.
R.; Stobbe, C. C.; Fenning, M. C.; Golberg, J. L.; Chapman, J. D. Cancer
Res. 1998, 58, 3571-3578.
(10) (a) Mazor, O.; Brandis, A.; Plaks, V.; Neumark, E.; Rosenbach-
Belkin, V.; Salomon, Y.; Scherz, A. Photochem. Photobiol. 2005, 81, 342-
351. (b) Nyman, E. S.; Hynninen, P. H. J. Photochem. Photobiol. B: Biol.
2004, 73, 1-28. (c) Koudinova, N. V.; Pinthus, J. H.; Brandis, A.; Brenner,
O.; Bendel, P.; Ramon, J.; Eshhar, Z.; Scherz, A.; Salomon, Y. Int. J. Cancer
2003, 104, 782-789. (d) Bonnett, R. Chemical Aspects of Photodynamic
Therapy; Gordon and Breach Science Publishers: Amsterdam, The
Netherlands, 2000. (e) Photodynamic Tumor Therapy. 2nd and 3rd
Generation Photosensitizers; Moser, J. G., Ed.; Harwood Academic
Publishers: Amsterdam, The Netherlands, 1998.
(11) (a) Wasielewski, M. R.; Svec, W. A. J. Org. Chem. 1980, 45, 1969-
1974. (b) Struck, A.; Cmiel, E.; Katheder, I.; Scha¨fer, W.; Scheer, H.
Biochim. Biophys. Acta 1992, 1101, 321-328. (c) Mironov, A. F.; Grin,
M. A.; Tsiprovskii, A. G.; Segenevich, A. V.; Dzardanov, D. V.; Golovin,
K. V.; Tsygankov, A. A.; Shim, Ya. K. Russ. J. Bioorg. Chem. 2003, 29,
190-197. (d) Mironov, A. F.; Grin, M. A.; Tsiprovskiy, A. G.; Kachala,
V. V.; Karmakova, T. A.; Plyutinskaya, A. D.; Yakubovskaya, R. I. J.
Porphyrins Phthalocyanines 2003, 7, 725-730. (e) Kozyrev, A. N.; Chen,
Y.; Goswami, L. N.; Tabaczynski, W. A.; Pandey, R. K. J. Org. Chem.
2006, 71, 1949-1960. (f) Sasaki, S-I.; Tamiaki, H. J. Org. Chem. 2006,
71, 2648-2654. (g) Gryshuk, A.; Chen, Y.; Goswami, L. N.; Pandey, S.;
Missert, J. R.; Ohulchanskyy, T.; Potter, W.; Prasad, P. N.; Oseroff, A.;
Pandey, R. K. J. Med. Chem. 2007, 50, 1754-1767.
(12) Shanmugathasan, S.; Johnson, C. K.; Edwards, C.; Matthews, E.
K.; Dolphin, D.; Boyle, R. W. J. Porphyrins Phthalocyanines 2000, 4, 228-
232.
(13) Shi, X.; Liebeskind, L. S. J. Org. Chem. 2000, 65, 1665-1671.
(14) Taniguchi, M.; Kim, M. N.; Ra, D.; Lindsey, J. S. J. Org. Chem.
2005, 70, 275-285.
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Tetrahedron 2007, 63, 3840-3849.
J. Org. Chem, Vol. 72, No. 14, 2007 5351

Fan et al.
TABLE 1. 1H NMR Chemical Shifts for Bacteriochlorins with Bromo Substituentsa
H-BC
H-BC-Br5
H-BC-Br3
H-BC-Br5Br13
H-BC-Br3Br13
MeO-BC
MeO-BC-Br15
position
δ
δ (∆δ)
δ (∆δ)
δ (∆δ)
δ (∆δ)
δ
δ (∆δ)
5
10
8.82
8.86
8.99 (+0.17)
8.83 (-0.03)
8.98 (+0.16)
8.62 (-0.24)
8.73 (-0.13)
8.52 (-0.34)
8.82 (+0.04)
8.77 (-0.04)
8.78
8.68
8.81
15
20
8.82
8.86
8.70 (-0.12)
8.81 (-0.05)
8.78 (-0.04)
8.62 (-0.24)
8.92 (+0.10)
8.83 (-0.03)
8.98 (+0.16)
8.62 (-0.24)
3
13
8.73
8.73
9.04 (+0.31)
8.70 (-0.03)
9.06 (+0.33)
8.94
8.63
8.98 (+0.04)
9.04 (+0.41)
8.71 (-0.02)
2a
12a
8.13
8.13
8.11 (-0.02)
8.08 (-0.05)
8.02 (-0.11)
8.10 (-0.03)
8.10 (-0.03)
7.98 (-0.15)
8.01 (-0.12)
8.01 (-0.12)
8.14
8.10
8.11 (-0.03)
8.10 (0)
a In CDCl3 at 298 K. Significant shifts (∆δ) are shown in bold.
former (58%) versus the latter (25%) sites. All further attempts
with variation of reaction conditions and halogenating agent
(including Br2/pyridine, NIS, or I2/(CF3CO2)2IC6H5/pyridine)
failed to give regioselective monobromination (see the Sup-
porting Information), and difficult separation of the resulting
mixtures limited the utility of this approach.
By contrast to the poor regioselectivity upon halogenation
of H-BC, treatment of the 5-methoxybacteriochlorin (MeO-
BC) with NBS in THF at room temperature for 30 min cleanly
afforded the corresponding 15-bromobacteriochlorin (MeO-BC-
Br15) in 85% yield (eq 1). In some cases a trace of a
substituted chlorins, wherein a downfield shift (0.32 ppm) was
observed of the â-pyrrolic proton adjacent to the meso-bromo
substituent.16 Introduction of a bromine atom at the â-position
causes the resonances from adjacent meso-protons (H5 or H15)
to shift downfield (∼0.16 ppm for H-BC-Br3 or H-BC-
Br3Br13). In addition, the resonances from the adjacent p-tolyl
protons (H2a or H12a) are shifted upfield (∼0.1 ppm) versus that
of H-BC. The latter observation is useful to confirm the presence
of â-bromo substitution in the crude mixture of bromobac-
teriochlorins, as well as to clarify the substitution pattern for
more highly substituted bacteriochlorins.
2. Deuteration of Bacteriochlorins. Deuteration has long
been employed to evaluate the reactivity of porphyrinic mac-
rocycles toward electrophilic attack.17 Woodward first reported
that chlorins possessing no meso substituents and a partial or
full complement of â-substituents undergo deuteration prefer-
entially at the meso sites (15- and 20-positions) flanking the
pyrroline ring rather than the meso sites (5, 10) distal to the
pyrroline ring.18 More recent studies of fully unsubstituted
chlorins showed that the meso positions flanking the pyrroline
ring (15- and 20-position) are the most reactive (among four
meso sites and six â-pyrrolic sites) toward deuteration in acidic
media.15 To our knowledge, no study of the deuteration of
bacteriochlorins has been reported.
In preparation for a study of bacteriochlorin deuteration, the
resonances from the meso- and the â-protons of H-BC and
MeO-BC were assigned by NOESY spectra (in TFA-d at
25 °C). Unlike chlorins, which gave selective meso- versus
â-substitution,15 a considerable amount of deuteration occurred
at the â-positions in TFA-d during the course of preliminary
spectral measurements (∼8 h at 25 °C). Indeed, 1H NMR
spectroscopic examination in CDCl3 of the isolated bacterio-
chlorin product in each case identified the deuterated product
to be H-BC-D3D13 (∼70% deuterated, partial deuteration at the
5- and 15-positions) or MeO-BC-D3D13 (∼60% deuterated,
partial deuteration at the 15-position) (Scheme 2).
It should be noted that the treatment of a free base bacterio-
chlorin with a strong acid affords the corresponding dication.
Indeed, H-BC (or MeO-BC) in TFA solution promptly under-
went protonation to form the putative H-BC-2H2+ (or MeO-
BC-2H2+). A small aliquot of the TFA solution was diluted
â-bromobacteriochlorin (putative 13-bromo derivative) was
observed in the crude reaction mixture. Iodination of MeO-BC
also was examined, but the expected 15-iodo product was not
obtained. The 15-position is the least hindered of the three open
meso sites (10, 15, 20) in MeO-BC; however, the regioselec-
tivity of bromination of MeO-BC versus H-BC, particularly
the preference for 15- versus 13-bromination, must stem in part
from an electronic effect of the 5-methoxy substituent.
1
The resonances in the H NMR spectra of the bromobacte-
riochlorins are assigned and summarized in Table 1. The
resonances from the protons adjacent to the bromine atom
exhibit characteristic shifts depending on the location at the
perimeter of the macrocycle. Introduction of a bromine atom
at the meso-position of a bacteriochlorin (H-BC or MeO-BC)
causes the resonances from the adjacent â-protons (H3 or H13)
to shift downfield (∼0.3 ppm for H-BC-Br5, H-BC-Br5Br13,
and MeO-BC-Br15). This result matches well with a previous
1H NMR spectroscopic study of analogous meso-bromo-
(16) Taniguchi, M.; Ptaszek, M.; McDowell, B. E.; Boyle, P. D.; Lindsey,
J. S. Tetrahedron 2007, 63, 3850-3863.
(17) (a) Grigg, R.; Trocha-Grimshaw, J.; Waring, L.; Leworthy, D.;
Regan, P. J. Chem. Soc., Chem. Commun. 1979, 557-559. (b) Broadhurst,
M. J.; Grigg, R.; Johnson, A. W. J. Chem. Soc. C 1971, 3681-3690. (c)
Broadhurst, M. J.; Grigg, R.; Johnson, A. W. J. Chem. Soc., Perkin Trans.
1 1972, 1124-1135.
(18) Woodward, R. B.; Skaric, V. J. Am. Chem. Soc. 1961, 83, 4676-
4678.
5352 J. Org. Chem., Vol. 72, No. 14, 2007

Functionalization of a Stable Synthetic Bacteriochlorin
SCHEME 2
with toluene and examined by absorption spectroscopy. The
bacteriochlorin dication exhibits a bathochromically shifted Qy
band [H-BC, 737 nm (ꢀ 130 000 M-1 cm-1);1 H-BC-2H2+, 796
nm (ꢀ 95 000 M-1 cm-1); MeO-BC, 732 nm (ꢀ 120 000 M-1
cm-1);1 MeO-BC-2H2+, 789 nm (ꢀ 85 000 M-1 cm-1)] (Figure
1). Identical spectra were obtained upon use of TFA-d. In each
case the spectrum of the free base bacteriochlorin was reobtained
upon neutralization with triethylamine, indicating the revers-
ibility of protonation and deprotonation.
The kinetics of the deuterium exchange process of the
bacteriochlorins (H-BC and MeO-BC) in neat TFA-d at 50 °C
was measured by 1H NMR spectroscopy. For example, dissolu-
tion of H-BC in neat TFA-d at 50 °C resulted in a steady
decrease over 1 h in the intensity of the resonance from H3
(8.67 ppm). By contrast, the intensity of the resonance from H5
(8.92 ppm) declined slowly whereas that of H10 (8.84 ppm) did
not show any change. Partial decomposition of the bacterio-
chlorin was observed after 3 h; thus, the data up to 2 h were
used for kinetic studies. The data obtained obeyed first-order
rate expressions quite closely, thereby enabling calculation of
rate constants k. The data are summarized in Table 2.
The key observations from the kinetic study are as follows:
(1) The rate constant for deuteration of MeO-BC increased in
order of 10- and 20- < 15- < 13- < 3-position. (2) The rate
constant for deuteration of H-BC increased in order of 10-, 20-
< 5-, 15- , 3-, 13-positions. (3) The rate constants for
deuteration of the meso-positions of bacteriochlorins were
slightly less than that for the corresponding meso-positions
(flanking the pyrroline ring; k15 ) 13 × 10-5 s-1; k20 ) 4.7 ×
10-5 s-1) of a fully unsubstituted chlorin (H2C) under identical
conditions,15 with no detectable â-deuteration.
The deuteration results were surprising in two regards. First,
the predominance of â-substitution versus meso-substitution was
unexpected, because chlorins undergo selective meso-substitu-
tion. It remains to be determined to what extent the rapid rate
of â-deuteration of the bacteriochlorins stems from the adjacent
p-tolyl groups. An effect of substituents in directing deuteration
in porphyrins was recently described.19 Second, the product
profiles were quite different upon deuteration and bromination
of the bacteriochlorins. Many possible mechanistic explanations
FIGURE 1. Absorption spectra (normalized) in toluene containing TFA
at room temperature: (a) H-BC (solid trace, λQ 737 nm) and H-BC-
y
2H2+ (dashed trace, λQ 796 nm) and (b) MeO-BC (solid trace, λQ
y
y
732 nm) and MeO-BC-2H2+ (dashed trace, λQ 789 nm).
y
TABLE 2. Rate Constants for Deuterium Exchange of
Bacteriochlorin Protonsa
rate constant k (×10-5) in s-1
H-BC
MeO-BC
â-positions
3
75
53
23
13
meso-positions
5
2
-
6
<2
-
15
10
20
b
-
b
a Pseudo-first-order rate constants measured in TFA-d at 50 °C. b Not
observed.
can be suggested for the different regiochemical outcome of
the two reactions. One explanation concerns the different
reactants present under the two reaction conditions (strong acid
versus neutral media). The presumed reactant that undergoes
deuterium exchange is the bacteriochlorin dication whereas the
reactant that undergoes bromination is the neutral, free base
bacteriochlorin.
3. Substitution at the 15-Position: (a) Suzuki Reaction.
The Suzuki coupling of MeO-BC-Br15 and dioxaborolanes
1a-c was carried out under standard conditions for use with
(19) Zhu, Y.; Silverman, R. B. J. Org. Chem. 2007, 72, 233-239.
J. Org. Chem, Vol. 72, No. 14, 2007 5353

Fan et al.
porphyrinic compounds.14,20,21 The boronic acid moiety was
employed as the dioxaborolane derivative to improve the
reaction yield and facilitate purification.22 The dioxaborolane-
containing reactants 1a and 1c for Suzuki coupling were
synthesized, whereas 1b was available commercially. Thus,
phenol 223 was treated with NaH in THF followed by condensa-
tion with tert-butyl bromoacetate to give compound 1a in 80%
yield (eq 2). The treatment of 3,5-diformylphenylboronic acid
with pinacol in dry THF at room temperature21 afforded the
corresponding dialkyl boronate 1c in 77% yield (eq 3). The
(5 and 20 mM, respectively) in the presence of Pd2(dba)3, Cs2-
CO3, and a phosphine ligand in THF. When DPEphos26 was
employed, the yield of BC-6 was 14%. The use of Xantphos27
rather than DPEphos gave BC-6 in 57% isolated yield (Table
3, entry 6).
4. Derivatization of Substituents at the 15-Position. The
3,5-diformylphenylbacteriochlorin BC-3 was treated to reductive
amination28 with a short oligoethylene glycol moiety bearing a
single amino group (eq 4). The reaction was carried out with
Suzuki coupling reactions were carried out in toluene/DMF (2:
1) at 90 °C for 18 h with modest concentrations of MeO-BC-
Br15 (10 mM) and 1a-c (20-40 mM) in the presence of
Pd(PPh3)4 (30 mol %) and K2CO3 (8 molar equiv). In so doing,
the corresponding bacteriochlorins BC-1-BC-3 were obtained
in 67% to 85% yield (Table 3, entries 1-3).
(b) Sonogashira Reaction. The Sonogashira coupling of
MeO-BC-Br15 and phenylethyne (1d) or 2-(triisopropylsilyl)-
ethyne (1e) was carried out under standard conditions for use
with porphyrinic substrates [2.4 mM MeO-BC-Br15, 7.2 mM
ethyne, 0.36 mM Pd2(dba)3, and 3.1 mM P(o-tol)3 in toluene/
TEA (5:1) at 60 °C].24 These conditions afforded reaction under
mild conditions, in dilute solution where porphyrinic compounds
are soluble, and in the absence of any copper reagents that might
insert into the bacteriochlorin core. Under these conditions, the
15-(phenylethynyl)bacteriochlorin BC-4 and 15-[2-(triisopro-
pylsilyl)ethynyl]bacteriochlorin BC-5 were obtained in 49% and
59% yield, respectively (Table 3, entries 4 and 5).
BC-3 and 3,6,9,12-tetraoxatridecylamine in 1:5 ratio in a dilute
solution (2 mM BC-3) in MeOH/THF (1:9) at room temperature
for 3 h. Workup including chromatography afforded the bis-
aminated bacteriochlorin product BC-7 in 86% yield (purity
∼95%). In addition, the TIPS group of BC-5 was removed upon
treatment with TBAF in THF affording BC-8 in 83% yield
(eq 5).
(c) Hartwig-Buchwald Reaction. The Hartwig-Buchwald
reaction of MeO-BC-Br15 and benzamide (1f) was carried out
under conditions that have been used previously for the
amidation of porphyrins.25 The coupling of MeO-BC-Br15 and
benzamide was carried out with use of modest concentrations
(20) (a) Shultz, D. A.; Gwaltney, K. P.; Lee, H. J. Org. Chem. 1998,
63, 769-774. (b) Hyslop, A. G.; Kellett, M. A.; Iovine, P. M.; Therien, M.
J. J. Am. Chem. Soc. 1998, 120, 12676-12677. (c) Zhou, X.; Chan, K. S.
J. Org. Chem. 1998, 63, 99-104.
5. Bacteriochlorin NMR Spectra. The 1H NMR spectra of
the substituted bacterichlorins were readily interpreted. Two
points merit comment: (1) The resonance from each â-pyrrole
(21) Yu, L.; Lindsey, J. S. Tetrahedron 2001, 57, 9285-9298.
(22) Murata, M.; Watanabe, S.; Masuda, Y. J. Org. Chem. 1997, 62,
6458-6459.
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(24) (a) Tomizaki, K.-Y.; Lysenko, A. B.; Taniguchi, M.; Lindsey, J. S.
Tetrahedron 2004, 60, 2011-2023. (b) Wagner, R. W.; Ciringh, Y.; Clausen,
C.; Lindsey, J. S. Chem. Mater. 1999, 11, 2974-2983. (c) Wagner, R. W.;
Johnson, T. E.; Li, F.; Lindsey, J. S. J. Org. Chem. 1995, 60, 5266-5273.
(25) Gao, G.-Y.; Chen, Y.; Zhang, X. P. Org. Lett. 2004, 6, 1837-1840.
(26) Chen, Y.; Zhang, X. P. J. Org. Chem. 2003, 68, 4432-4438.
(27) (a) Yin, J.; Buchwald, S. L. Org. Lett. 2000, 2, 1101-1104. (b)
Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043-6048.
(28) Borch, R. F.; Bernstein, M. D.; Durst, H. D. J. Am. Chem. Soc.
1971, 93, 2897-2904.
5354 J. Org. Chem., Vol. 72, No. 14, 2007

Functionalization of a Stable Synthetic Bacteriochlorin
TABLE 3. Pd-Mediated Substitutiona of MeO-BC-Br15
a Conditions: (A) Pd(PPh3)4, K2CO3, toluene/DMF (2:1), Ar, 90 °C, 18 h; (B) Pd2(dba)3, P(o-tol)3, toluene/TEA (5:1), Ar, 60 °C, 18 h; (C) Cs2CO3,
Pd2(dba)3, Xantphos, THF, reflux, Ar, 18 h.
proton (H3, H13) in each bacteriochlorin examined herein
TABLE 4. Absorption Spectral Features of Bacteriochlorinsa
(including H-BC, MeO-BC, bromobacteriochlorins, and 5-meth-
oxy-15-substituted bacteriochlorins) appears as a doublet (J ≈
2 Hz). Such splitting is attributed to coupling with the pyrrolic
NH proton. Analogous splitting is observed in free base
porphyrins at low temperature, where N-H tautomerization
processes are very slow. Such tautomerization processes in
bacteriochlorins are energetically less favorable owing to the
presence of the two pyrroline rings, and hence are observed at
room temperature.29 A similar observation and interpretation
was reported for 5,10,15,20-tetraphenylbacteriochlorin.30 Further
supporting evidence stems from 1H NMR studies of metal
chelates of H-BC, wherein the splitting disappears and the
â-pyrrole proton (H3, H13) resonates as a singlet (unpublished
data). (2) The resonance from each meso-proton (H10, H20)
appears as a singlet. The presence of only four protons at the
perimeter of the macrocycle (H3, H10, H13, and H20) renders
a Absorption spectra were recorded in toluene at room temperature.
1
the H NMR spectra of the 5,15-disubstituted bacteriochlorins
exceptionally simple. Moreover, the chemical shift of H13
depends on the nature of the 15-substituent whereas that of H3
(and H10 and H20) is relatively unchanged (see the Supporting
Information).
b Ratio of the intensities of the Qy and B bands. c Full-width at half-
maximum in nm.
as BC-1 to BC-8 are summarized in Table 4. The absorption
spectra of two bacteriochlorins are shown in Figure 2. The key
points of interest include the effects of substituents on (1) the
extent of absorption in the red or near-IR region, which can be
assessed by the position of the long-wavelength (Qy) absorption
6. Bacteriochlorin Absorption Spectra. The features of the
absorption spectrum of the bacteriochlorin MeO-BC as well
(29) Scheer, H.; Katz, J. J. In Porphyrins and Metalloporphyrins; Smith,
K. M., Ed.; Elsevier Scientific Publishing Co.: Amsterdam, The Nether-
lands, 1975; pp 399-524.
(30) Whitlock, H. W., Jr.; Hanauer, R.; Oester, M. Y.; Bower, B. K. J.
Am. Chem. Soc. 1969, 91, 7485-7489.
maximum (λQ ) and the ratio of the intensity of the Qy versus
y
the B band (IQ /IB), and (2) the sharpness of the long-wavelength
y
absorption band, which can be assessed by the full-width at
half-maximum (fwhm) of the band.16,31,32 Increased absorption
J. Org. Chem, Vol. 72, No. 14, 2007 5355

Fan et al.
to afford a black green solid (122 mg, 85%): 1H NMR δ -2.00
(br, 1H), -1.80 (br, 1H), 1.91 (s, 6H), 1.92 (s, 6H), 2.61 (s, 6H),
4.38-4.42 (br, 2H), 4.49 (s, 3H), 4.48-4.52 (br, 2H), 7.56-7.62
(m, 4H), 8.08-8.14 (m, 4H), 8.77 (s, 1H), 8.82 (s, 1H), 8.98 (d, J
) 2.0 Hz, 1H), 9.04 (d, J ) 2.0 Hz, 1H); λabs (CH2Cl2) 377, 523,
735 nm; LD-MS obsd 658.5 and 660.5; FAB-MS obsd 658.2328,
calcd 658.2307 (C39H39BrN4O).
tert-Butyl [4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
phenoxy]acetate (1a). A solution of 223 (220 mg, 1.00 mmol) in
dry THF (20 mL) was treated with NaH (48.2 mg, 2.00 mmol) at
room temperature for 10 min. tert-Butyl bromoacetate (220 µL,
1.50 mmol) was added, and the mixture was stirred at room
temperature for 18 h. TLC analysis [silica, hexanes/ethyl acetate
(5:1)] showed only one spot. The reaction mixture was diluted with
ethyl acetate and washed with brine. The organic layer was
separated, dried (Na2SO4), concentrated, and chromatographed
[silica, hexanes/ethyl acetate (5:1)] to afford a colorless solid (268
mg, 80%): mp 90-91 °C; 1H NMR δ 1.33 (s, 12H), 1.48 (s, 9H),
4.53 (s, 2H), 6.85-6.90 (m, 2H), 7.73-7.78 (m, 2H); 13C NMR δ
25.1, 28.2, 65.6, 82.6, 83.8, 114.1, 136.7, 160.6, 168.0. Anal. Calcd
for C18H27BO5: C, 64.69; H, 8.14. Found: C, 64.75; H, 8.22.
Compound 1a, prepared via a different route, has been described
previously with limited characterization data.33
FIGURE 2. Absorption spectra (normalized) in toluene at room
temperature of MeO-BC (solid line, λQ 732 nm) and BC-4 (dashed
y
line, λQ 754 nm).
y
3,5-Diformyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ben-
zaldehyde (1c). A solution of 3,5-diformylphenylboronic acid (178
mg, 1.00 mmol) in dry THF (10 mL) was treated with pinacol (142
mg, 1.20 mmol) at room temperature for 18 h. The reaction mixture
became yellow, and TLC analysis (silica, CH2Cl2) showed only
one spot. The reaction mixture was concentrated to a light yellow
oil. Trituration with hexanes gave a solid, which was filtered and
in the red or near-IR region is of interest for a variety of
photochemical applications. In this regard, the presence of the
15-N-benzamido group (BC-6) or a 15-aryl group (BC-1, BC-
2, BC-3, and BC-7) causes a bathochromic shift of the Qy band
by 3-6 nm, whereas a 15-ethynyl substituent (BC-4, BC-5,
and BC-8) causes a bathochromic shift of the Qy band by 18-
1
dried to give a colorless solid (200 mg, 77%): mp 89-91 °C; H
22 nm. Relatively little change in the IQ /IB ratio occurs among
y
NMR δ 1.39 (s, 12H), 8.46-8.47 (m, 1H), 8.55-8.56 (m, 2H),
10.14 (s, 2H); 13C NMR δ 25.1, 85.0, 132.4, 136.6, 141.6, 191.50,
191.51 (the resonance of the 4° carbon, which is close to the oxygen
atom, is overlapped by that of residual CHCl3). Anal. Calcd for
C14H17BO4: C, 64.65; H, 6.59. Found: C, 64.69; H, 6.65.
the substituents examined herein versus that of MeO-BC (IQ /
y
IB ) 0.91), although a slight relative increase in the Qy band
intensity occurs upon 15-ethynyl substitution. In all cases, the
long-wavelength band remains quite sharp, with fwhm ∼20 nm.
In one case where fluorescence was examined, excitation of
the 15-phenylethynylbacteriochlorin (BC-4) at 551 nm (Qx band)
resulted in emission at 761 nm with a fluorescence quantum
yield (Φf) of 0.16, which compares well with that of MeO-BC
(Φf ) 0.18) and H-BC (Φf ) 0.14).1
7. Outlook. The 5-methoxybacteriochlorin MeO-BC can be
tailored with a variety of groups in a selective manner by
regioselective bromination followed by Pd-mediated coupling.
The introduction of an aryl or N-benzamido group causes hardly
any change in absorption features, whereas the introduction of
an ethynyl group shifts the long-wavelength band bathochro-
mically by ∼20 nm. Such facile tailoring should open the door
to a number of applications where strong near-IR absorption is
required.
Suzuki Coupling: 15-[4-(tert-Butoxycarbonylmethoxy)phe-
nyl]-5-methoxy-8,8,18,18-tetramethyl-2,12-bis(4-methylphenyl)-
bacteriochlorin (BC-1). A mixture of MeO-BC-Br15 (26.3 mg,
40.0 µmol, 10 mM), 1a (40.1 mg, 120 µmol), Pd(PPh3)4 (13.9 mg,
12.0 µmol), and K2CO3 (66.3 mg, 480 µmol) was placed into a 10
mL Schlenk flask, which was then pump-purged three times with
argon. Toluene/DMF [4 mL (2:1)] was added, and the reaction
mixture was stirred at 90 °C. After 18 h, the mixture was
concentrated to dryness and diluted with CH2Cl2. The organic layer
was washed with aqueous NaHCO3, separated, dried (Na2SO4), and
filtered. The filtrate was concentrated and chromatographed [silica,
hexanes/CH2Cl2 (1:2)] to afford a green solid (21.2 mg, 67%): 1H
NMR δ -1.84 (br, 1H), -1.62 (br, 1H), 1.59 (s, 9H), 1.81 (s, 6H),
1.91 (s, 6H), 2.57 (s, 3H), 2.61 (s, 3H), 4.00 (s, 2H), 4.39 (s, 2H),
4.50 (s, 3H), 4.74 (s, 2H), 7.17-7.20 (m, 2H), 7.49-7.53 (m, 2H),
7.57-7.60 (m, 2H), 7.74-7.79 (m, 2H), 7.97-8.01 (m, 2H), 8.12-
8.17 (m, 2H), 8.16 (d, J ) 1.6 Hz, 1H), 8.81 (s, 1H), 8.82 (s, 1H),
8.94 (d, J ) 1.6 Hz, 1H); λabs (toluene) 378, 519, 735 nm; LD-MS
obsd 787.0; FAB-MS obsd 786.4156, calcd 786.4145 (C51H54N4O4).
5-Methoxy-15-(4-pyridyl)-8,8,18,18-tetramethyl-2,12-bis(4-
methylphenyl)bacteriochlorin (BC-2). A mixture of MeO-BC-
Br15 (26.3 mg, 40.0 µmol, 10 mM), 1b (53.5 mg, 160 µmol),
Pd(PPh3)4 (13.9 mg, 12.0 µmol), and K2CO3 (88.5 mg, 640 µmol)
was heated in toluene/DMF [4 mL (2:1)] at 90 °C for 18 h,
whereupon TLC analysis [silica, CH2Cl2/ethyl acetate (10:1)]
showed two main spots (the bacteriochlorin debromination byprod-
uct MeO-BC, and the desired product). Standard workup including
chromatography [silica, CH2Cl2/ethyl acetate (10:1)] afforded a
green solid (22.3 mg, 85%): 1H NMR δ -1.92 (br, 1H), -1.65
(br, 1H), 1.83 (s, 6H), 1.92 (s, 6H), 2.57 (s, 3H), 2.61 (s, 3H), 3.99
Experimental Section
15-Bromination: 5-Bromo-15-methoxy-8,8,18,18-tetramethyl-
2,12-bis(4-methylphenyl)bacteriochlorin (MeO-BC-Br15). A so-
lution of MeO-BC1 (127 mg, 219 µmol, 2.0 mM) in THF (110
mL) was treated with NBS (38.9 mg, 219 µmol, 2.0 mM) at room
temperature for 15 min. TLC analysis [silica, hexanes/CH2Cl2 (1:
1)] showed only one spot. The reaction mixture was diluted with
CH2Cl2 and washed with saturated aqueous NaHCO3. The organic
layer was dried (Na2SO4) and filtered. The filtrate was concentrated.
The residue was chromatographed [silica, hexanes/CH2Cl2 (1:1)]
(31) Laha, J. K.; Muthiah, C.; Taniguchi, M.; McDowell, B. E.; Ptaszek,
M.; Lindsey, J. S. J. Org. Chem. 2006, 71, 4092-4102.
(32) Kee, H. L.; Kirmaier, C.; Tang, Q.; Diers, J. R.; Muthiah, C.;
Taniguchi, M.; Laha, J. K.; Ptaszek, M.; Lindsey, J. S.; Bocian, D. F.;
Holten, D. Photochem. Photobiol. 2007, in press.
(33) Albert, M. J.; Drewry, D. H.; Miller, D. D.; Bamborough, P. WO
2004/084813 A2.
5356 J. Org. Chem., Vol. 72, No. 14, 2007

Functionalization of a Stable Synthetic Bacteriochlorin
(s, 2H), 4.41 (s, 2H), 4.51 (s, 3H), 7.49-7.55 (m, 2H), 7.57-7.61
(m, 2H), 7.82-7.85 (m, 2H), 7.96-8.00 (m, 2H), 8.09 (d, J ) 2.0
Hz, 1H), 8.12-8.16 (m, 2H), 8.84 (s, 1H), 8.86 (s, 1H), 8.92-
8.96 (m, 2H), 8.98 (d, J ) 2.0 Hz, 1H); λabs (toluene) 378, 518,
736 nm; LD-MS obsd 658.0; FAB-MS obsd 657.3494, calcd
657.3468 (C44H43N5O).
mixture was concentrated to dryness and diluted with CH2Cl2. The
organic layer was washed with water, separated, dried (Na2SO4),
and filtered. The filtrate was concentrated and chromatographed
[silica, hexanes/ethyl acetate (3:1) followed by CH2Cl2/ethyl acetate
(10:1)] to afford a black solid (13 mg, 46%): 1H NMR (THF-d8 +
DMSO-d6) δ -1.95 (br, 1H), -1.81 (br, 1H), 1.84 (s, 6H), 1.89
(s, 6H), 2.54 (s, 3H), 2.57 (s, 3H), 4.31 (s, 2H), 4.40 (s, 2H), 4.49
(s, 3H), 7.58-7.63 (m, 4H), 7.68-7.74 (m, 3H), 8.06-8.10 (m,
2H), 8.15-8.19 (m, 2H), 8.40-8.44 (m, 2H), 8.80 (s, 1H), 8.81
(s, 1H), 8.82 (d, J ) 2.0 Hz, 1H), 9.03 (d, J ) 2.0 Hz, 1H), 11.5
(s, 1H); λabs (toluene) 374, 513, 737 nm; LD-MS obsd 699.6; FAB-
MS obsd 699.3562, calcd 699.3573 (C46H45N5O2).
15-(3,5-Diformylphenyl)-5-methoxy-8,8,18,18-tetramethyl-2,-
12-bis(4-methylphenyl)bacteriochlorin (BC-3). A mixture of
MeO-BC-Br15 (26.4 mg, 40.0 µmol, 10 mM), 1c (20.8 mg, 80.0
µmol), Pd(PPh3)4 (13.8 mg, 12.0 µmol), and K2CO3 (44.2 mg, 160
µmol) was heated in toluene/DMF [4 mL (2:1)] at 90 °C for 18 h,
whereupon TLC analysis [silica, hexanes/CH2Cl2 (1:1)] showed
three main spots: MeO-BC-Br15, MeO-BC, and product. Standard
workup including chromatography [silica, hexanes/CH2Cl2 (1:1)
followed by CH2Cl2] afforded a black solid (23.1 mg, 81%): 1H
NMR δ -1.92 (br, 1H), -1.61 (br, 1H), 1.83 (s, 6H), 1.93 (s, 6H),
2.56 (s, 3H), 2.61 (s, 3H), 3.96 (s, 2H), 4.42 (s, 2H), 4.52 (s, 3H),
7.48-7.52 (m, 2H), 7.57-7.61 (m, 2H), 7.94 (d, J ) 2.0 Hz, 1H),
7.93-7.98 (m, 2H), 8.12-8.17 (m, 2H), 8.66 (d, J ) 1.5 Hz, 2H),
8.68 (d, J ) 1.5 Hz, 1H), 8.84 (s, 1H), 8.87 (s, 1H), 9.00 (d, J )
2.0 Hz, 1H), 10.33 (s, 2H); λabs (toluene) 376, 520, 738 nm; LD-
MS obsd 712.8; FAB-MS obsd 712.3433, calcd 712.3413
(C47H44N4O3).
Sonogashira Coupling: 5-Methoxy-8,8,18,18-tetramethyl-2,-
12-bis(4-methylphenyl)-15-(2-phenylethynyl)bacteriochlorin (BC-
4). A mixture of MeO-BC-Br15 (23 mg, 36 µmol, 2.4 mM),
phenylacetylene (12 µL, 0.11 mmol, 7.2 mM), Pd2(dba)3 (4.9 mg,
5.3 µmol, 0.36 mM), and P(o-tol)3 (14 mg, 46 µmol, 3.1 mM) was
placed into a 100 mL Schlenk flask, which was then pump-purged
three times with argon. Toluene/TEA [15 mL (5:1)] was added,
and the reaction mixture was stirred at 60 °C. After 7 h,
phenylacetylene (12 µL, 0.11 mmol, 7.2 mM), Pd2(dba)3 (4.9 mg,
5.3 µmol, 0.36 mM), and P(o-tol)3 (14 mg, 46 µmol, 3.1 mM) were
added. After 16 h, the mixture was concentrated to dryness. TLC
analysis [silica, hexanes/THF (17:3)] showed three main spots
(starting material, product and an unknown compound). Purification
entailed removal of palladium reagents by silica-pad filtration
[hexanes/CH2Cl2 (1:1)] followed by three additional chromatogra-
phy columns [silica, hexanes/THF (17:3); silica, hexanes/CHCl3
(1:1); silica, hexanes/CH2Cl2 (1:1)], which afforded a black solid
(11 mg, 49%): 1H NMR δ -1.49 (br, 1H), -1.28 (br, 1H), 1.90
(s, 6H), 1.92 (s, 6H), 2.61 (s, 6H), 4.35 (s, 2H), 4.48 (s, 3H), 4.62
(s, 2H), 7.43-7.45 (m, 1H), 7.49-7.53 (m, 2H), 7.56-7.61 (m,
4H), 7.88-7.90 (m, 2H), 8.09-8.14 (m, 4H), 8.75 (s, 1H), 8.77
(s, 1H), 8.90 (d, J ) 2.0 Hz, 1H), 9.15 (d, J ) 2.0 Hz, 1H); λabs
(toluene) 387, 551, 754 nm; λem (λexc 551 nm) 761 nm, Φf ) 0.16;
LD-MS obsd 680.7; FAB-MS obsd 680.3516, calcd 680.3515
(C47H44N4O).
5-Methoxy-8,8,18,18-tetramethyl-2,12-bis(4-methylphenyl)-
15-[3,5-bis(5,8,11,14-tetraoxa-2-azapentadecyl)phenyl]bacterio-
chlorin (BC-7). A solution of BC-3 (7.1 mg, 10 µmol) and 3,6,9,12-
tetraoxatridecylamine (10 mg, 50 µmol) in THF/MeOH (5 mL, 9:1)
was treated with acetic acid (3.0 mg, 50 µmol) and NaBH3CN (2.8
mg, 40 µmol). The reaction mixture was stirred at room temperature
for 4 h. The crude mixture was concentrated, diluted in CH2Cl2,
and washed with water. The organic layer was separated, dried (Na2-
SO4), and concentrated. The residue was chromatographed [silica,
MeOH/DMF (1:1)]. The collected eluate was concentrated under
high vacuum, diluted with CH2Cl2, and washed with water. The
organic layer was separated, dried (Na2SO4), and concentrated to
afford a red-black solid (9.4 mg, 86%): 1H NMR δ -1.86 (br,
1H), -1.63 (br, 1H), 1.81 (s, 6H), 1.92 (s, 6H), 2.56 (s, 3H), 2.61
(s, 3H), 2.95-2.97 (m, 4H), 3.22 (s, 3H), 3.25 (s, 3H), 3.35-3.67
(m, 24H), 3.99 (s, 2H), 4.03 (s, 4H), 4.21-4.22 (m, 4H), 4.40 (s,
2H), 4.51 (s, 3H), 7.48-7.61 (m, 6H), 7.67-7.73 (m, 3H), 7.96-
8.00 (m, 2H), 8.12-8.17 (m, 3H), 8.80 (s, 1H), 8.83 (s, 1H), 8.95
(d, J ) 2.0 Hz, 1H); λabs (toluene) 377, 519, 735 nm; LD-MS obsd
1094.5; FAB-MS obsd 1095.6556, calcd 1095.6535 [(M + H)+,
M ) C65H86N6O9].
5-Ethynyl-15-methoxy-8,8,18,18-tetramethyl-2,12-bis(4-methyl-
phenyl)bacteriochlorin (BC-8). A solution of BC-5 (14 mg, 19
µmol) in THF (1.9 mL) was treated with TBAF/THF (1.0 M, 56
µL, 56 mmol) in an ice bath for 15 min. The reaction mixture was
concentrated, diluted with CH2Cl2, and washed with aqueous
NaHCO3. The organic layer was separated, dried (Na2SO4),
concentrated, and chromatographed [silica, hexanes/CH2Cl2
(2:1)] to afford a green solid (9.3 mg, 83%): 1H NMR δ -1.64
(br, 1H), -1.41 (br, 1H), 1.90 (s, 12H), 2.61 (s, 6H), 3.92 (s, 1H),
4.35 (s, 2H), 4.48 (s, 3H), 4.54 (s, 2H), 7.56-7.60 (m, 4H), 8.08-
8.12 (m, 4H), 8.77 (s, 1H), 8.80 (s, 1H), 8.90 (d, J ) 2.0 Hz, 1H),
9.09 (d, J ) 2.0 Hz, 1H); λabs (toluene) 383, 533, 750 nm;
LD-MS obsd 604.8; FAB-MS obsd 604.3227, calcd 604.3202
(C41H40N4O).
5-Methoxy-8,8,18,18-tetramethyl-2,12-bis(4-methylphenyl)-
15-[2-(triisopropylsilyl)ethynyl]bacteriochlorin (BC-5). A mix-
ture of MeO-BC-Br15 (26 mg, 40 µmol, 2.5 mM), (triisopropylsilyl)-
acetylene (27 µL, 120 µmol), Pd2(dba)3 (11 mg, 12 µmol), and
P(o-tol)3 (16 mg, 52 µmol) was heated in toluene/TEA [16 mL
(5:1)] at 60 °C for 16 h. Standard workup including chromatography
[silica, hexanes/CH2Cl2 (2:1)] afforded a red-black solid (18 mg,
59%): 1H NMR δ -1.58 (br, 1H), -1.37 (br, 1H), 1.37-1.39 (m,
21H), 1.89 (s, 12H), 2.60 (s, 3H), 2.61 (s, 3H), 4.34 (s, 2H), 4.47
(s, 3H), 4.52 (s, 2H), 7.56-7.62 (m, 4H), 8.08-8.14 (m, 4H), 8.76
(s, 1H), 8.77 (s, 1H), 8.89 (d, J ) 2.0 Hz, 1H), 9.10 (d, J ) 2.0
Hz, 1H); λabs (toluene) 385, 540, 753 nm; LD-MS obsd 760.8; FAB-
MS obsd 760.4567, calcd 760.4536 (C50H60N4OSi).
Acknowledgment. This research was supported by the NIH
(GM-36238). Mass spectra were obtained at the Mass Spec-
trometry Laboratory for Biotechnology at North Carolina State
University. Partial funding for the facility was obtained from
the North Carolina Biotechnology Center and the National
Science Foundation.
Supporting Information Available: Spectral data (absorption,
1H NMR, LD-MS) for all new bacteriochlorins including spectral
assignments; description of deuteration experiments and data,
and additional information concerning experimental proce-
dures. This material is available free of charge via the Internet at
http://pubs.acs.org.
Hartwig-Buchwald Coupling: 15-(N-Benzamido)-5-meth-
oxy-8,8,18,18-tetramethyl-2,12-bis(4-methylphenyl)bacteriochlo-
rin (BC-6). A mixture of MeO-BC-Br15 (26 mg, 40 µmol, 5 mM),
benzamide (19 mg, 80 µmol), Pd2(dba)3 (3.6 mg, 4.0 µmol),
Xantphos (4.8 mg, 8.0 µmol), and Cs2CO3 (104 mg, 320 µmol)
was placed into a 10 mL Schlenk flask, which was then pump-
purged three times with argon. Distilled THF (8 mL) was added,
and the reaction mixture was stirred at reflux. After 18 h, the
JO070785S
J. Org. Chem, Vol. 72, No. 14, 2007 5357