Two complementary routes to 7-substituted chlorins. Partial mimics of chlorophyll b

Article abstract of DOI:10.1021/jo701500d

(Chemical Equation Presented) Chlorophyll a and chlorophyll b exhibit distinct spectra yet differ only in the nature of a single substituent (7-methyl versus 7-formyl, respectively). Two complementary approaches have been developed for the synthesis of 7-

Full text of DOI:10.1021/jo701500d

Two Complementary Routes to 7-Substituted Chlorins. Partial
Mimics of Chlorophyll b
Chinnasamy Muthiah, Marcin Ptaszek, Tien M. Nguyen, Kyle M. Flack, and
Jonathan S. Lindsey*
Department of Chemistry, North Carolina State UniVersity, Raleigh, North Carolina 27695-8204
jlindsey@ncsu.edu
ReceiVed July 10, 2007
Chlorophyll a and chlorophyll b exhibit distinct spectra yet differ only in the nature of a single substituent
(7-methyl versus 7-formyl, respectively). Two complementary approaches have been developed for the
synthesis of 7-substituted chlorins. The first approach is a de novo route wherein 2,9-dibromo-5-p-
tolyldipyrromethane (Eastern half) and 9-formyl-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin (Western half)
undergo acid-catalyzed condensation followed by metal-mediated oxidative cyclization. The resulting
zinc chlorin is sterically uncongested and bears (1) a geminal dimethyl group in the reduced, pyrroline
ring, (2) a bromo substituent at the 7-position, and (3) a p-tolyl group at the 10-position. The second
approach entails regioselective 7-bromination of a 10,15-diarylchlorin that lacks a substituent at the
5-position. In an extension of this latter approach, a 5,15-diarylchlorin that lacks a substituent at the
10-position undergoes regioselective bromination at the 8-position. The introduction of a TIPS-ethynyl,
acetyl, or formyl group at the 7-position was achieved using Pd-catalyzed reactions with the corresponding
7-bromochlorin. In the 10-p-tolyl-substituted zinc chlorins, the series of substituents (7-TIPS-ethynyl,
7-acetyl, 7-formyl) progressively causes (1) a bathochromic shift in the absorption maximum of the B
band (405 to 426 nm) and (2) a hypsochromic shift in the position of the Qy band (605 to 598 nm). The
trends mirror those for chlorophyll b versus chlorophyll a but are of lesser magnitude. Taken together,
the facile access to chlorins that bear auxochromes at the 7-position enables wavelength tunability and
provides the foundation for fundamental spectroscopic studies.
Introduction
intense B (Soret) band at 429 nm and a Qy band at 661 nm of
nearly comparable intensity.2 Chlorophyll b exhibits a B band
at 453 nm and a Qy band at 642 nm; the former is more intense
than that of chlorophyll a, while the latter is less intense.2 Thus,
the presence of the 7-formyl versus 7-methyl group causes a
bathochromic shift of the B band but a hypsochromic shift of
the Qy band and also alters the ratio of the B and Qy band
intensities. The profound spectral differences owing to the
change of a single substituent render 7-substituted chlorins
valuable synthetic targets for fundamental spectroscopic studies
Chlorophyll a and chlorophyll b are the two green pigments
that underlie plant photosynthesis. Chlorophylls a and b each
bear a 3-vinyl group, an isocyclic ring spanning the 13-15-
positions, and a 7-methyl versus 7-formyl group, respectively,
attached to the chlorin macrocycle. The presence of a conjuga-
tive substituent at the 3-position (vinyl) and the 13-position (keto
group of the isocyclic ring) substantially alters the spectral
properties of the chlorin (Figure 1).1 Chlorophyll a exhibits an
(1) Scheer, H. In Chlorophylls; Scheer, H., Ed.; CRC Press: Boca Raton,
FL, 1991; pp 3-30.
(2) Strain, H. H.; Thomas, M. R.; Katz, J. J. Biochim. Biophys. Acta
1963, 75, 306-311.
10.1021/jo701500d CCC: $37.00 © 2007 American Chemical Society
Published on Web 09/06/2007
7736
J. Org. Chem. 2007, 72, 7736-7749

Two Complementary Routes to 7-Substituted Chlorins
of chlorins bearing substituents at designated sites has enabled
a set of fundamental spectroscopic studies.7,18-26 The objective
of the work described herein is to gain access to 7-substituted
chlorins and thereby complete this one facet of chlorin
chemistry.
The retrosynthetic analyses shown in Scheme 1 constitute
two distinct and complementary approaches to 7-substituted
chlorins. One strategy introduces the group destined to occupy
the chlorin 7-position at an early stage of an established route
to chlorins, wherein a Western half and an Eastern half undergo
acid-catalyzed condensation followed by metal-mediated oxida-
tion. The groups in the Western and Eastern halves are carried
through to the chlorin. In this route, the group destined for the
chlorin 7-position must be introduced into the dipyrromethane
that constitutes the Eastern half.
A second strategy relies on derivatization of an intact chlorin.
The â-positions of ring B (distal to the reduced ring, ring D)
are known to be reactive to a variety of reagents. Indeed,
reduction (using catalytic hydrogenation,27 diimide,28 or sodium
isopentoxide29) or Vic-dihydroxylation30,31 of a chlorin typically
affords the bacteriochlorin. Ring B also is susceptible to reagents
that characteristically react with isolated double bonds, such as
dipolarophiles.32-34 In this regard, bromination of a meso-
tetraarylchlorin affords the corresponding 7,8-dibromochlorin.33
FIGURE 1. The absorption spectra of chlorophyll a and chlorophyll
b in diethyl ether at room temperature.
CHART 1
(15) Ptaszek, M.; Bhaumik, J.; Kim, H.-J.; Taniguchi, M.; Lindsey, J.
S. Org. Process Res. DeV. 2005, 9, 651-659.
(16) Ptaszek, M.; McDowell, B. E.; Lindsey, J. S. J. Org. Chem. 2006,
71, 4328-4331.
as well as for potential applications in light harvesting or the
life sciences.
(17) Kim, H.-J.; Dogutan, D. K.; Ptaszek, M.; Lindsey, J. S. Tetrahedron
2007, 63, 37-55.
In 1994, we began a program to develop rational synthetic
routes to stable, tailorable chlorins. To achieve stability, each
chlorin (dihydroporphyrin) bears a geminal dimethyl group in
the reduced, pyrroline ring to block adventitious dehydrogena-
tion. The program began by building off of prior synthetic routes
to naturally occurring non-photosynthetic pigments that also
contain a geminal dimethyl group in the pyrroline ring.3 The
ensuing development and application of these routes has now
provided access to every peripheral site of the chlorin macro-
cycle with the exception of the 7-site. The sites include the 2-,
3-, 5-, 8-, 10-, 12-, 13-, 15-, 17-, 18-, and 20-positions (Chart
1).4-12 An approach for introducing the isocyclic ring, which
spans positions 13 and 15, has been established.13 Streamlined
routes to chlorin precursors also are in hand.14-17 The availability
(18) Muthukumaran, K.; Loewe, R. S.; Kirmaier, C.; Hinden, E.;
Schwartz, J. K.; Sazanovich, I. V.; Diers, J. R.; Bocian, D. F.; Holten, D.;
Lindsey, J. S. J. Phys. Chem. B 2003, 107, 3431-3442.
(19) Kirmaier, C.; Hinden, E.; Schwartz, J. K.; Sazanovich, I. V.; Diers,
J. R.; Muthukumaran, K.; Taniguchi, M.; Bocian, D. F.; Lindsey, J. S.;
Holten, D. J. Phys. Chem. B 2003, 107, 3443-3454.
(20) Taniguchi, M.; Ra, D.; Kirmaier, C.; Hindin, E. K.; Schwartz, J.
K.; Diers, J. R.; Bocian, D. F.; Lindsey, J. S.; Knox, R. S.; Holten, D. J.
Am. Chem. Soc. 2003, 125, 13461-13470.
(21) Hindin, E.; Kirmaier, C.; Diers, J. R.; Tomizaki, K.-Y.; Taniguchi,
M.; Lindsey, J. S.; Bocian, D. F.; Holten, D. J. Phys. Chem. B 2004, 108,
8190-8200.
(22) Taniguchi, M.; Ptaszek, M.; McDowell, B. E.; Boyle, P. D.; Lindsey,
J. S. Tetrahedron 2007, 63, 3850-3863.
(23) 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, 83, doi: 10.1111/j.1751-
1097.2007.00150.x.
(3) Montforts, F.-P.; Gerlach, B.; Ho¨per, F. Chem. ReV. 1994, 94, 327-
347.
(24) 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, 83, doi: 10.1111/j.1751-
1097.2007.00151.x.
(25) Muthiah, C.; Taniguchi, M.; Kim, H.-J.; Schmidt, I.; Kee, H. L.;
Holten, D.; Bocian, D. F.; Lindsey, J. S. Photochem. Photobiol. 2007, doi
10.1111/j.1751-1097.2007.00195.x.
(26) Stromberg, J. R.; Marton, A.; Kee, H. L.; Kirmaier, C.; Diers, J.
R.; Muthiah, C.; Taniguchi, M.; Lindsey, J. S.; Bocian, D. F.; Meyer, G.
J.; Holten, D. J. Phys. Chem. C 2007, ASAP (JP0749928).
(27) Dorough, G. D.; Miller, J. R. J. Am. Chem. Soc. 1952, 74, 6106-
6108.
(28) Whitlock, H. W., Jr.; Hanauer, R.; Oester, M. Y.; Bower, B. K. J.
Am. Chem. Soc. 1969, 91, 7485-7489.
(29) Inhoffen, H. H.; Buchler, J. W.; Thomas, R. Tetrahedron Lett. 1969,
10, 1141-1144.
(30) Pandey, R. K.; Shiau, F.-Y.; Isaac, M.; Ramaprasad, S.; Dougherty,
T. J.; Smith, K. M. Tetrahedron Lett. 1992, 33, 7815-7818.
(31) Bru¨ckner, C.; Dolphin, D. Tetrahedron Lett. 1995, 36, 9425-9428.
(32) Yon-Hin, P.; Wijesekera, T. P.; Dolphin, D. Tetrahedron Lett. 1991,
32, 2875-2878.
(4) Strachan, J.-P.; O’Shea, D. F.; Balasubramanian, T.; Lindsey, J. S.
J. Org. Chem. 2000, 65, 3160-3172.
(5) Balasubramanian, T.; Strachan, J. P.; Boyle, P. D.; Lindsey, J. S. J.
Org. Chem. 2000, 65, 7919-7929.
(6) Taniguchi, M.; Ra, D.; Mo, G.; Balasubramanian, T.; Lindsey, J. S.
J. Org. Chem. 2001, 66, 7342-7354.
(7) Taniguchi, M.; Kim, H.-J.; Ra, D.; Schwartz, J. K.; Kirmaier, C.;
Hindin, E.; Diers, J. R.; Prathapan, S.; Bocian, D. F.; Holten, D.; Lindsey,
J. S. J. Org. Chem. 2002, 67, 7329-7342.
(8) Taniguchi, M.; Kim, M. N.; Ra, D.; Lindsey, J. S. J. Org. Chem.
2005, 70, 275-285.
(9) Laha, J. K.; Muthiah, C.; Taniguchi, M.; McDowell, B. E.; Ptaszek,
M.; Lindsey, J. S. J. Org. Chem. 2006, 71, 4092-4102.
(10) Ptaszek, M.; McDowell, B. E.; Taniguchi, M.; Kim, H.-J.; Lindsey,
J. S. Tetrahedron 2007, 63, 3826-3839.
(11) Taniguchi, M.; Ptaszek, M.; McDowell, B. E.; Lindsey, J. S.
Tetrahedron 2007, 63, 3840-3849.
(12) Muthiah, C.; Bhaumik, J.; Lindsey, J. S. J. Org. Chem. 2007, 72,
5839-5842.
(13) Laha, J. K.; Muthiah, C.; Taniguchi, M.; Lindsey, J. S. J. Org. Chem.
2006, 71, 7049-7052.
(33) Shea, K. M.; Jaquinod, L.; Khoury, R. G.; Smith, K. M. Tetrahedron
2000, 56, 3139-3144.
(34) Silva, A. M. G.; Tome´, A. C.; Neves, M. G. P. M. S.; Silva, A. M.
S.; Cavaleiro, J. A. S. J. Org. Chem. 2005, 70, 2306-2314.
(14) Laha, J. K.; Dhanalekshmi, S.; Taniguchi, M.; Ambroise, A.;
Lindsey, J. S. Org. Process Res. DeV. 2003, 7, 799-812.
J. Org. Chem, Vol. 72, No. 20, 2007 7737

Muthiah et al.
or synthesized de novo, to the corresponding 7-formyl group.36
The chief alternative approach to 7-substituted chlorins entails
semisynthesis of naturally occurring pigments. Although semi-
synthesis has been widely exploited with chlorophyll a and
analogues,37-47 less work has been carried out with chlorophyll
b. Modification of the 7-formyl group of chlorophyll b (and
pheophorbide analogues) has yielded 7-substituents such as
hydroxymethyl,48 carboxylic acid,37,41 carbomethoxy,41 vinyl,49
hydrazone,50,51 aminomethyl,52 and other aldehyde addition
products (acetal, oxime, cyanohydrin, and hemithioacetal).37,39
Modifications also have been carried out on the 7-formyl group
in the chlorins bacteriochlorophyll e53 and bacteriochlorophyll
f.54 A recent comprehensive review of such modifications is
available.55
SCHEME 1
In this paper, we describe the development of the two routes
shown in Scheme 1. One of the resulting 7-bromochlorins was
derivatized with potential auxochromes such as acetyl, TIPS-
ethynyl, and formyl groups. The absorption spectral properties
of the corresponding zinc and free base chlorins have been
characterized. Taken together, this work provides access to
chlorins of interest for a variety of fundamental studies.
Results and Discussion
I. Synthesis of 7-Substituted Chlorins via a Functionalized
Eastern Half. A. Synthesis of Eastern Halves. The synthesis
of a bromo-substituted dipyrromethane (Eastern half) that is
suitable for conversion to the corresponding 7-bromochlorin
presented a number of challenges. Two successful routes were
developed. The first route, shown in Scheme 2, relies on the
use of an R-alkylthio-substituted pyrrole.56 The R-alkylthio unit
(36) Inhoffen, H. H.; Ja¨ger, P.; Ma¨hlhop, R. Liebigs Ann. Chem. 1971,
749, 109-116.
(37) Seely, G. R. in The Chlorophylls; Vernon, L. P., Seely, G. R., Eds.;
Academic Press: New York, 1966; pp 67-109.
(38) Boxer, S. G. Biochim. Biophys. Acta 1983, 726, 265-292.
(39) Hynninen, P. H. In Chlorophylls; Scheer, H., Ed.; CRC Press: Boca
Raton, FL, 1991; pp 145-209.
(40) Wasielewski, M. R. Chem. ReV. 1992, 92, 435-461.
(41) Osuka, A.; Wada, Y.; Shinoda, S. Tetrahedron 1996, 52, 4311-
4326.
(42) Tamiaki, H.; Kouraba, M. Tetrahedron 1997, 53, 10677-10688.
(43) Kozyrev, A. N.; Alderfer, J. L.; Robinson, B. C. Tetrahedron 2003,
59, 499-504.
(44) Balaban, T. S.; Tamiaki, H.; Holzwarth, A. R. Top. Curr. Chem.
2005, 258, 1-38.
In principle, both â-positions (7 and 8) in ring B of a chlorin
should have equal reactivity. Our thinking was that the presence
of a bulky group at the 10-position might cause substitution to
favor the 7- versus 8-position.
(45) Wang, J.-J.; Imafuku, K.; Shim, Y. K.; Jiang, G.-J. J. Heterocycl.
Chem. 2005, 42, 835-840.
(46) Katterle, M.; Holzwarth, A. R.; Jesorka, A. Eur. J. Org. Chem. 2006,
414-422.
In both strategies, the preferred initial substituent was the
bromo atom because palladium-mediated coupling reactions can
then be utilized to introduce diverse substituents such as aryl,
alkyne, amine, and acyl moieties. In addition, the chlorins of
initial interest are those that contain few other substituents so
that the effects of 7-substituents on spectral properties can be
clearly delineated. To our knowledge, routes that enable facile
preparation of a variety of 7-substituted chlorins have not
previously been described. Jacobi described an elegant synthesis
of a series of chlorins that bear 7-alkanoic acids of different
lengths, but this route has not been extended to accommodate
the distinct types of substituents envisaged herein.35 Inhoffen
described the transformation of the 7-methyl group of chlorin-
e6-trimethyl ester, a relay species derived from chlorophyll a
(47) Kelley, R. F.; Tauber, M. J.; Wasielewski, M. R. J. Am. Chem.
Soc. 2006, 128, 4779-4791.
(48) Oba, T.; Masada, Y.; Tamiaki, H. Bull. Chem. Soc. Jpn. 1997, 70,
1905-1909.
(49) Michalski, T. J.; Hunt, J. E.; Hindman, J. C.; Katz, J. J. Tetrahedron
Lett. 1985, 26, 4875-4878.
(50) (a) Wetherell, H. R.; Hendrickson, M. J. J. Org. Chem. 1959, 24,
710-711. (b) Kenner, G. W.; McCombie, S. W.; Smith, K. M. J. Chem.
Soc., Perkin Trans. 1 1973, 2517-2523. (c) Losev, A.; Mauzerall, D.
Photochem. Photobiol. 1983, 38, 355-361.
(51) Baker, E. W.; Corwin, A. H.; Klesper, E.; Wei, P. E. J. Org. Chem.
1968, 33, 3144-3148.
(52) Davis, R. C.; Ditson, S. L.; Fentiman, A. F.; Pearlstein, R. M. J.
Am. Chem. Soc. 1981, 103, 6823-6826.
(53) Simpson, D. J.; Smith, K. M. J. Am. Chem. Soc. 1988, 110, 1753-
1758.
(54) Tamiaki, H.; Kubo, M.; Oba, T. Tetrahedron 2000, 56, 6245-6257.
(55) Pavlov, V. Yu.; Ponomarev, G. V. Chem. Heterocycl. Comp. 2004,
40, 393-425.
(56) Thamyongkit, P.; Bhise, A. D.; Taniguchi, M.; Lindsey, J. S. J.
Org. Chem. 2006, 71, 903-910.
(35) O’Neal, W. G.; Roberts, W. P.; Ghosh, I.; Wang, H.; Jacobi, P. A.
J. Org. Chem. 2006, 71, 3472-3480.
7738 J. Org. Chem., Vol. 72, No. 20, 2007

Two Complementary Routes to 7-Substituted Chlorins
Mukaiyama reagent 158 at -78 °C gave the known59 2-acylpyr-
role 2 in 71% yield. The regioselective bromination of 2 was
achieved in the presence of NBS following an established
procedure8 to obtain 4-bromo-2-(4-methylbenzoyl)pyrrole (3).
The regiochemistry of the monobromo-monoacylpyrrole 3 was
established by NMR spectroscopy (1H-1H 2D COSY and NOE
experiments). Reduction of 3 with NaBH4 gave the correspond-
ing pyrrole-carbinol derivative, which upon condensation with
a stoichiometric amount of R-decylthiopyrrole 456 in the
presence of InCl3 (10 mol %) afforded dipyrromethane 5 in 83%
yield. Attempts to formylate 5 at the R-position adjacent to the
â-bromo group either with the Vilsmeier reagent or with
MesMgBr and phenyl formate16 afforded a mixture of products.
To achieve regioselective formylation, we considered deactivat-
ing the decylthio group in 5 by means of oxidation to the
sulfone.56 However, the oxidation of 5 with m-CPBA in CH2-
Cl2 at 0 °C for 5 h gave dark polymeric materials, which
prompted us to examine the direct use of compound 5 as the
Eastern half in the chlorin-forming reaction.
SCHEME 2
B. Chlorin Formation. The condensation of compound 5
(Eastern half) and 9-formyltetrahydrodipyrrin 617 (Western half)
in CH2Cl2 containing methanolic p-TsOH‚H2O under argon
afforded a clear reddish-brown solution over 40-50 min. The
reaction mixture was neutralized (with 2,2,6,6-tetramethylpip-
eridine), concentrated, and treated to metal-mediated oxidative
cyclization with Zn(OAc)2 and AgOTf in refluxing CH3CN
exposed to air for 18 h. The 7-bromochlorin ZnC-Br7T10 was
obtained in 7.6% yield after silica column chromatography. The
decylthio group was obviously cleaved during the course of
macrocycle formation. This route provides direct access to
7-bromochlorins, albeit in low yield. Chlorin ZnC-Br7T10 was
1
characterized by absorption spectroscopy, H NMR spectros-
copy, LD-MS, and FAB-MS analyses.
Given the poor leaving ability of the alkylthio group, we
explored routes that employed dipyrromethanes other than 5
(see the Supporting Information). The best result was obtained
with the desdecylthio analogue of 5, 2-bromo-5-p-tolyldipyr-
romethane 7. The synthesis of 7 is shown in Scheme 3.
Reduction of 3 with NaBH4 gave the corresponding pyrrole-
carbinol species, which upon treatment with excess pyrrole under
acidic conditions5 afforded dipyrromethane 7 in 52% yield after
column chromatography. Treatment of 7 with 1.0 molar equiv
of NBS at -78 °C gave the crude 2,9-dibromo-5-p-tolyldipyr-
romethane (7-R-Br), where bromination occurred at the R-posi-
tion in the pyrrole ring lacking the â-bromo group. This novel
dibromodipyrromethane was condensed with Western half 6
under the standard conditions of p-TsOH‚H2O catalysis. The
putative tetrahydrobiladiene-ab formed was subjected to metal-
mediated oxidative cyclization (2,2,6,6-tetramethylpiperidine,
Zn(OAc)2, and AgOTf) in refluxing acetonitrile in the presence
of air for 14 h, affording the zinc chelate of the 7-bromochlorin
(ZnC-Br7T10) in 41% yield. The ZnC-Br7T10 prepared in this
manner agreed in all respects with the sample of ZnC-Br7T10
prepared as shown in Scheme 2. The structure of ZnC-Br7T10
was unambiguously established by X-ray crystallography as well
as by 2D NMR spectroscopy (see the Supporting Information).
In summary, the route shown in Scheme 3 provides a concise
entre´e to 7-bromochlorins and has the following noteworthy
features: (i) the dipyrromethane 7 is prepared without use of
any protecting group (cf. 5); (ii) the labile dibromodipyr-
romethane intermediate 7-R-Br can be prepared and used
directs electrophilic aromatic substitution toward the R′-position
and enables the use of a stoichiometric amount of alkylthiopy-
rrole and pyrrole-carbinol to form the target dipyrromethane.
The synthesis begins by acylation of pyrrole with a Mu-
kaiyama reagent in the standard manner.57,58 Thus, treatment
of pyrrole with MesMgBr at room temperature followed by
(57) (a) Araki, M.; Sakata, S.; Takei, H.; Mukaiyama, T. Bull. Chem.
Soc. Jpn. 1974, 47, 1777-1780. (b) Nicolaou, K. C.; Claremon, D. A.;
Papahatjis, D. P. Tetrahedron Lett. 1981, 22, 4647-4650.
(58) Zaidi, S. H. H.; Muthukumaran, K.; Tamaru, S.-I.; Lindsey, J. S. J.
Org. Chem. 2004, 69, 8356-8365.
(59) White, J.; McGillivray, G. J. Org. Chem. 1977, 42, 4248-4251.
J. Org. Chem, Vol. 72, No. 20, 2007 7739

Muthiah et al.
SCHEME 3
SCHEME 4
following simple workup; and (iii) the isolated yield of the
7-bromochlorin is several-fold greater than that of the route
employing the R-decylthio masking group.
C. Chlorin Derivatization. The 7-bromochlorin was deriva-
tized with three groups (TIPS-ethynyl, acetyl, formyl) to
investigate their effects on the absorption spectral properties of
chlorins. These groups serve as potent auxochromes upon
introduction at the 3- and/or 13-positions of chlorins.9,12,24 Each
derivatization was carried out at small scale and employed
palladium-mediated coupling reactions. The palladium-mediated
reactions were carried out under copper-free conditions to ensure
no unwanted copper transmetalation of zinc chlorins or copper
insertion into free base chlorins (Scheme 4).
1. 7-Ethynylation. The synthesis of 7-TIPS-ethynylchlorin
ZnC-E7T10 was carried out by Sonogashira coupling.9,60 Thus,
the reaction of ZnC-Br7T10 and (triisopropylsilyl)acetylene in
the presence of Pd2(dba)3 and P(o-tol)3 gave 7-TIPS-ethynyl-
chlorin Zn-E7T10 in 68% yield. Demetalation of ZnC-E7T10
with TFA in CH2Cl2 at room temperature gave the free base
chlorin FbC-E7T10 in 82% yield.
2. 7-Acetylation. The synthesis of a 7-acetylchlorin began
by treatment of ZnC-Br7T10 with TFA in CH2Cl2 at room
temperature to obtain the free base 7-bromochlorin FbC-Br7T10
in 87% yield. The coupling9 of FbC-Br7T10 (15 mM) and
tributyl(1-ethoxyvinyl)tin (60 mM) in the presence of 20 mol
% of (PPh3)2PdCl2 in THF for 20 h followed by hydrolysis with
10% aqueous HCl gave 7-acetylchlorin FbC-A7T10 in 69%
yield. A streamlined procedure including demetalation, Pd
coupling, and acidic workup gave FbC-A7T10 in 66% yield
starting from ZnC-Br7T10 (not shown). The free base 7-ace-
tylchlorin FbC-A7T10 was metalated with Zn(OAc)2‚2H2O to
obtain ZnC-A7T10 in 88% yield.
(60) Wagner, R. W.; Ciringh, Y.; Clausen, C.; Lindsey, J. S. Chem.
Mater. 1999, 11, 2974-2983.
7740 J. Org. Chem., Vol. 72, No. 20, 2007

Two Complementary Routes to 7-Substituted Chlorins
SCHEME 5
substituents with various steric bulk (mesityl, p-tolyl, pentyl)
at the 10-position. In a complementary study, we wanted to
examine the bromination of a 5,15-disubstituted, 10-unsubsti-
tuted chlorin under analogous conditions.
This strategy required preparation of a series of 10,15-
disubstituted (and one 5,15-disubstituted) chlorins. The target
15-substituted chlorins were obtained by bromination of 10- (or
5-) substituted chlorins followed by Suzuki coupling of the
resulting 15-bromo derivatives. Note that all transformations
(bromination and Suzuki coupling) were performed on the free
base rather than corresponding Zn(II) complexes. The free base
chlorins are easier to purify than the Zn(II) complexes.
A. Synthesis of 5- or 10-Substituted Chlorins. The known
chlorins FbC and FbC-M10 (and their corresponding Zn(II)
complexes) were prepared according to reported procedures.10
The known chlorin ZnC-T5 was prepared by a streamlined
procedure10 wherein all steps (bromination of the 1-acyldipyr-
romethane, carbonyl reduction, acid-catalyzed condensation, and
metal-mediated oxidative cyclization) were carried out in one
flask over a 1 day period in 20% overall yield (see the
Supporting Information). Demetalation of ZnC-T5 with TFA
afforded FbC-T5.
The 10-substituted chlorins ZnC-T10 and ZnC-Pn10 were
prepared by standard procedures10 as shown in Scheme 6. The
synthesis of chlorin ZnC-T10 began with known 5-p-tolyldipyr-
romethane 8a.61 Treatment16 of a solution of 8a in THF at room
temperature with 2 molar equiv of MesMgBr and then at
-78 °C with 2 molar equiv of phenyl formate afforded 1-formyl-
5-p-tolyldipyrromethane (9a) in 36% yield. Following the
streamlined chlorin synthesis,10 9a was treated with 1.0 molar
equiv of NBS at -78 °C to give the crude 9-bromo-1-formyl-
5-p-tolyldipyrromethane (Eastern half). Condensation of the
latter with tetrahydrodipyrrin 1015 (Western half) in CH2Cl2
containing methanolic p-TsOH‚H2O afforded a clear reddish-
brown solution over 40-50 min. Neutralization with 2,2,6,6-
tetramethylpiperidine afforded the crude tetrahydrobiladiene-
ab as a yellow solid, which was subjected to metal-mediated
oxidative cyclization [2,2,6,6-tetramethylpiperidine, Zn(OAc)2,
and AgOTf in refluxing acetonitrile in the presence of air] for
18 h. The resulting zinc chelate of the 10-p-tolylchlorin (ZnC-
T10) was obtained in 37% yield. Treatment of ZnC-T10 with
TFA gave the free base chlorin FbC-T10 in 92% yield.
3. 7-Formylation. The synthesis of a 7-formylchlorin em-
ployed reductive carbonylation.12 Thus, treatment of ZnC-
Br7T10 (10 mM) with sodium formate (25 mM) in the presence
of (PPh3)2PdCl2 (20 mol %) and PPh3 (20 mol %) in DMF at
108 °C under an atmosphere of CO afforded the 7-formylchlorin
ZnC-F7T10 in 37% yield.
Formylation of 5-pentyldipyrromethane 8b14 under Vilsmeier
conditions afforded 1-formyldipyrromethane 9b in 28% yield.
Bromination of 9b provided 9-bromo-1-formyl-5-pentyldipyr-
romethane, which was treated in the same manner as described
for 9a to provide ZnC-Pn10 in 26% yield. Demetalation of ZnC-
Pn10 with dilute TFA provided FbC-Pn10 in 81% yield.
II. Synthesis of 7-Substituted Chlorins by Regioselective
Bromination of an Intact Chlorin. Our previous studies have
shown that the electrophilic bromination of a fully unsubstituted
chlorin (bearing the 18,18-dimethyl group) proceeds selectively
at the 15-position.8,11 To determine the second-most reactive
site in the chlorin macrocycle, we examined the bromination
of a chlorin that bears an aryl substituent at the 15-position.
Thus, treatment of FbC-P15 with 1 equiv of NBS in THF at
room temperature afforded an inseparable, nearly equimolar
mixture of two monobromochlorins (Scheme 5). NMR analysis
(1H NMR, NOESY, COSY) showed that one of the components
in the mixture was the 7-bromochlorin FbC-Br7P15 and the
second was almost certainly the 8-bromochlorin FbC-Br8P15.
Treatment of FbC-P15 with 2 molar equiv of NBS under the
same conditions afforded the 7,8-dibromochlorin FbC-Br7,8P15.
We hypothesized that formation of FbC-Br8P15 might be
suppressed by introduction of a bulky substituent at the 10-
position. Thus, we set out to examine the regioselectivity of
bromination of chlorins that bear a 15-phenyl group and
B. Masking the 15-Position of 5- or 10-Substituted Chlo-
rins. The bromination of chlorins that bear a substituent at the
5- or 10-position was performed in THF (2 mM) at room
temperature.11 The reaction of FbC-T5, FbC-T10, and FbC-
Pn10 was typically complete within 30 min and provided the
corresponding 15-bromochlorin (FbC-T5Br15, FbC-T10Br15,
FbC-Pn10Br15) in a yield of 54-62% (Scheme 7). A small
amount of an unidentified dibromochlorin and the starting
material typically also were isolated from each reaction mixture.
The 15-bromo-10-mesitylchlorin FbC-M10Br15 was previously
prepared in like manner from FbC-M10.11
(61) Zaidi, S. H. H.; Fico, R. M., Jr.; Lindsey, J. S. Org. Process Res.
DeV. 2006, 10, 118-134.
J. Org. Chem, Vol. 72, No. 20, 2007 7741

Muthiah et al.
SCHEME 6
SCHEME 7
An aryl group at the 15-position of a chlorin was introduced
by Suzuki coupling of the 15-bromochlorin under conditions
employed previously with chlorins.8,11,23 Thus, reaction of a
15-bromochlorin with 4,4,5,5-tetramethyl-2-phenyl-1,3,2-diox-
aborolane in the presence of Pd(PPh3)4 (30 mol %) and K2CO3
afforded the corresponding 15-phenylchlorin in 50-80% yield.
Each reaction also provided a small amount (∼10%) of the
debrominated chlorin (detected by NMR spectroscopy and LD-
MS). Such byproducts typically exhibited polarity similar to
that of the desired 15-phenylchlorin and required repetitive
column chromatography using a quite nonpolar eluent [e.g.,
hexanes/toluene (1:2)] to obtain the target 15-phenylchlorin
(FbC-T5P15, FbC-T10P15, FbC-M10P15, and FbC-Pn10P15) in
acceptable purity.
C. Bromination of 15-Substituted Chlorins. Bromination
of the 10-arylchlorin FbC-M10P15 or FbC-T10P15 provided the
corresponding 7-bromochlorin FbC-Br7M10P15 or FbC-Br7T10P15
in 66 or 63% yield, respectively (Scheme 8). TLC analysis of
the crude reaction mixture in each case showed three spots: a
trace of unidentified, easily separable dibromochlorin of un-
SCHEME 8
known structure; the expected FbC-Br7P15 as the dominant
species; and a small amount of unreacted starting material. TLC
analysis of each purified 7-substituted chlorin also showed one
spot; however, given that FbC-Br7P15 and FbC-Br8P15 have
comparable polarity, this was insufficient proof of homogeneity.
LD-MS obviously cannot distinguish the two isomers. Proof of
7742 J. Org. Chem., Vol. 72, No. 20, 2007

Two Complementary Routes to 7-Substituted Chlorins
TABLE 1. Spectral Properties of Chlorinsa
SCHEME 9
λ
B (fwhm)
in nm
λQ (fwhm)
∆ν
y
b
c
compound
in nm
IB/IQ
(cm-1
)
y
chlorophyll ad
chlorophyll bd
Bchl ce
429 (39)
453 (22)
433
661 (17)
642 (16)
663
1.29
2.84
1.54
3.78
4.1
3.2
5.6
6.2
6.6
2.08
4.92
2.8
3.8
4.5
0
448
0
325
0
55
0
194
194
0
297
0
Bchl ee
462
649
ZnC-T10
405 (13)
410 (14)
421 (14)
426 (18)
428 (19)
411
605 (12)
603 (12)
605 (12)
598 (13)
598 (13)
668
ZnC-Br7T10
ZnC-E7T10
ZnC-A7T10
ZnC-F7T10
Me Pheo af
Me Pheo bf
FbC-T10
436
655
405 (34)
407 (34)
415 (35)
420 (17)
635 (9)
635 (9)
639 (10)
634 (11)
FbC-Br7T10
FbC-E7T10
FbC-A7T10
0
-99
25
homogeneity came from 1H NMR spectroscopy, which showed
only one chlorin. Taking into consideration the sensitivity of
1H NMR spectroscopy, the purity of the sample was estimated
to be >95%. Thus, any 8-bromochlorin formed was at the <5%
level.
On the other hand, bromination of 10-pentylchlorin FbC-
Pn10P15 provided a rather complex mixture of products. The
main fraction consisted of an inseparable mixture of two
components in ∼3:1 ratio. The major component proved to be
the 7-substituted chlorin FbC-Br7Pn10P15, whereas the minor
component is tentatively assigned as the 20-substituted chlorin
FbC-Pn10P15Br20. Thus, the presence of an aryl, but not pentyl,
group at the 10-position enables facile access via bromination
to the 7-bromochlorin.
9.1
a In toluene at room temperature unless noted otherwise. b Ratio of the
intensities of the B and Qy bands. c The spectral shift of the Qy band relative
to that of the corresponding benchmark compound (chlorophyll a, bacte-
riochlorophyll c, ZnC-T10, methyl pheophorbide a, or FbC-T10). A negative
value indicates a bathochromic shift; a positive value indicates a hypso-
chromic shift. d In diethyl ether.2 e Bacteriochlorophyll in acetone.62
f Methyl pheophorbide in THF.63,64
CHART 2
Bromination of FbC-T5P15 (which lacks a 10-substituent)
provided the corresponding 8-bromochlorin FbC-T5Br8P15 in
65% yield (Scheme 9). A small amount of another bromochlorin,
tentatively assigned as 20-bromochlorin FbC-T5P15Br20, was
readily separated and isolated in ∼6% yield. The small quantity
obtained of the latter product precluded 2D NMR analysis, and
the assignment of the structure remains provisional. This route
constitutes a simple method for preparing 8-bromochlorins.
The regiochemistry of bromination of the chlorins was
determined on the basis of 2D NMR spectroscopy (gCOSY and
1
NOESY). The characteristic features of the H NMR spectra
of FbC-Br7M10P15, FbC-Br7T10P15, and FbC-T5Br8P15 include
the following: (1) disappearance of two resonances (doublets)
attributed to H7 and H8; and (2) appearance of a new singlet,
attributed to H8 (H7 in the case of FbC-T5Br8P15) at ∼8.40-
1
8.65 ppm. The full assignment of the H NMR spectra for 7-
and 8-substituted chlorins is provided in the Supporting
Information. The identity of FbC-Br7,8P15 was established by
1
comparison of the H NMR spectrum of the isolated product
with that of FbC-P15. The disappearance of resonances attributed
to H7 and H8 was observed, whereas the chemical shifts of the
other resonances remained unchanged.
III. Spectroscopic Studies of Chlorins. The chlorins were
characterized by absorption spectroscopy, LD-MS, FAB-MS,
1H NMR spectroscopy, and, where permitted by solubility and
sample size, 13C NMR spectroscopy. The absorption spectra of
the 7-substituted chlorins (in toluene at room temperature) are
summarized in Table 1. For comparison, the spectral parameters
also are listed for chlorophylls a and b (see Figure 1), the related
chlorins bacteriochlorophylls c and e,1,62 and the free base
chlorins methyl pheophorbides63 a and b (Chart 2). The latter
are free base analogues of chlorophylls a and b wherein the
phytyl ester has been converted to a methyl ester.
The presence of the 7-substituents examined herein causes a
change of the position of the absorption bands in the blue region
(B band) and in the red region (Qy band). In general, the
7-substituents cause a bathochromic shift of the B band and a
hypsochromic shift of the Qy band. This is the same trend
observed for chlorophyll b versus chlorophyll a, and bacterio-
chlorophyll c versus bacteriochlorophyll e, though the magnitude
of the effect is less pronounced for the synthetic chlorins
(62) Porra, R. J. In Chlorophylls and Bacteriochlorophylls. Biochemistry,
Biophysics, Functions and Applications; Grimm, B., Porra, R. J., Ru¨diger,
W., Scheer, H., Eds.; Springer: Dordrecht, The Netherlands; pp 95-107.
(63) Hynninen, P. H.; Lo¨tjo¨nen, S. Synthesis 1980, 539-541.
J. Org. Chem, Vol. 72, No. 20, 2007 7743

Muthiah et al.
band [IB/IQ ratio ) 6.6 (or 6.2)]. These results indicate the
y
strong dependence of the substitution site at the perimeter of
the chlorin macrocycle for a given auxochrome to elicit a given
spectral change.
Outlook
Two complementary routes have been developed to gain
access to 7-substituted chlorins. The first route employs reaction
of a bromo-substituted Eastern half with a Western half to give
the 7-bromochlorin. The second route employs 7-bromination
of a 10,15-diarylchlorin. The former route is synthetically more
demanding than the latter but has broader scope owing to the
lack of requirements for substituents at the 10- and 15-positions.
The presence of carbonyl substituents (acetyl, formyl) at the
7-position causes a bathochromic shift of the B band and a
hypsochromic shift of the Qy band. However, the magnitude of
both shifts was substantially less than that observed in the
naturally occurring chlorophylls. The latter possess a keto group
(in the isocyclic ring) and a vinyl group that are positioned in
conjugation with the chromophore along the y-axis (which
bisects rings A and C). The magnitude of the shift also was
less than that observed in the naturally occurring bacteriochlo-
rophylls c and e, which contain the isocyclic ring but not the
vinyl group. Realizing the full magnitude of the spectral
difference observed due to 7-methyl versus 7-formyl substituents
in the natural compounds likely may also require the presence
of the keto-bearing isocyclic ring.
We note that, in a simple chlorin lacking any substituents,
the 7- and 8-positions are identical owing to their positions on
opposite sides of the mirror plane that includes the x-axis of
the molecule and that bisects rings B and D; however, in
chlorophylls or other chlorins that bear an unsymmetrical pattern
of substituents, a substituent at the 7- versus 8-position is not
necessarily expected to cause identical effects. Further study
with synthetic analogues is required to delineate this issue.
Regardless, the zinc chelate of the 7-formylchlorin (ZnC-F7T10)
or 7-acetylchlorin (ZnC-A7T10) already results in a Qy band
positioned at 598 nm, which is shorter than that for any synthetic
zinc chlorin prepared to date. The zinc chlorin (ZnC) lacking
any substituents other than the 18,18-dimethyl group in the
reduced ring absorbs at 603 nm,22 and the corresponding chlorin
with a single aryl group (e.g., ZnC-T10) absorbs at 605 nm. In
conjunction with other synthetic chlorins that we have prepared,
the long-wavelength absorption band can now be tuned with
fine precision from 598 to 667 nm (zinc chlorins) or 633 to
687 nm (free base chlorins).12,22,24
FIGURE 2. Absorption spectra (normalized) in toluene at room
temperature of ZnC-T10 (solid square), ZnC-E7T10(open square), ZnC-
A7T10 (solid circle), and ZnC-F7T10 (open circle).
examined here. By contrast, the presence of the same types of
substituents at the 3- or 13-position causes a bathochromic shift
of both the B band and the Qy band.9 Relatively few other
chlorins bearing 7-substituents are available for systematic
comparison, given that the known 7-conjugating substituents
other than formyl include carboxylic acid,37 carbomethoxy,41
vinyl,49 imine,50,51 and cyano.65 The presence of an ammonium
point charge at the 7-position also has been examined.52 The
absorption spectra of the ZnC-T10 series of compounds are
shown in Figure 2 (see the Supporting Information for additional
spectra).
The major observations concerning the synthetic chlorins
prepared herein are as follows:
(1) A 7-TIPS-ethynyl group causes a bathochromic shift of
16 nm in the B band region [ZnC-E7T10 (421 nm) versus ZnC-
T10 (405 nm)], whereas the position of the Qy band is unchanged
[ZnC-E7T10 (605 nm) versus ZnC-T10 (605 nm)]. This behavior
is different from that of the 13-substituted chlorin ZnC-M10E13
(M ) mesityl) where the presence of the ethynyl groups causes
a bathochromic shift of both the B and Qy bands (413, 627 nm).
(2) The presence of the acetyl group at the 7-position causes
a bathochromic shift of 21 nm of the B band [ZnC-A7T10
(426 nm) versus ZnC-T10 (405 nm)], whereas the Qy band was
shifted hypsochromically [ZnC-A7T10 (598 nm) versus ZnC-
T10 (605 nm)]. The IB/IQ ratio increased from 4.1 to 6.2.
y
(3) In the case of 7-formylchlorin ZnC-F7T10, the B and Qy
bands appear at 428 and 598 nm, respectively. Similar to that
of the 7-acetyl group, here also there occurred a bathochromic
shift of the B band, a hypsochromic shift of the Qy band, and
Experimental Section
an increase in the IB/IQ ratio (from 4.1 to 6.6).
y
Finally, the spectrum of the 7-formylchlorin ZnC-F7T10 (or
7-acetylchlorin ZnC-A7T10) can be compared with that of
analogous 13-substituted chlorins bearing a 10-aryl group. The
13-formylchlorin ZnC-M10F13 (or 13-acetylchlorin ZnC-
M10A13) exhibits principal absorption bands at 418 and 634 nm
2-(4-Methylbenzoyl)pyrrole (2). Following a general proce-
dure,58 a solution of pyrrole (2.20 g, 33.0 mmol) in THF (35 mL)
under argon was treated with MesMgBr (33 mL, 1.0 M THF
solution) for 15 min. The solution was cooled to -78 °C. Then a
solution of Mukaiyama reagent 1 (8.00 g, 16.6 mmol) in THF (17
mL) was added. The reaction mixture was stirred at -78 °C for 20
min followed by room temperature for 20 min. Then the reaction
mixture was quenched by the addition of saturated aqueous NH4-
Cl. The resulting mixture was extracted with CH2Cl2. The organic
layer was separated, washed with water, dried (Na2SO4), and
concentrated. The resulting solid was chromatographed [silica,
hexanes/CH2Cl2/ethyl acetate (8:1:1)] to give a yellow solid
(2.19 g, 71%): mp 120-121 °C (dec) [lit.59 mp 118-119 °C]; 1H
NMR δ 2.43 (s, 3H), 6.33-6.40 (m, 1H), 6.84-6.90 (m, 1H),
7.10-7.20 (m, 1H), 7.28 (d, J ) 8.2 Hz, 2H), 7.82 (d, J ) 8.2 Hz,
(or 418 and 632 nm) and IB/IQ ratio of 2.2 (or 2.2).12,23 Thus,
y
moving the formyl (or acetyl) group from the 13-position to
the 7-position results in a 36 nm (or 34 nm) hypsochromic shift
of the Qy band, a 10 (or 8) nm bathochromic shift of the B
band, and much greater relative absorption of the B versus Qy
(64) Dixon, J. M.; Taniguchi, M.; Lindsey, J. S. Photochem. Photobiol.
2005, 81, 212-213.
(65) Nichol, A. W. J. Chem. Soc. (C) 1970, 903-910.
7744 J. Org. Chem., Vol. 72, No. 20, 2007

Two Complementary Routes to 7-Substituted Chlorins
2H), 9.66 (br s, 1H); 13C NMR δ 21.6, 98.5, 120.4, 124.9, 129.3,
129.4, 131.2, 135.0, 143.3, 184.1. Anal. Calcd for C12H11NO: C,
77.81; H, 5.99; N, 7.56. Found: C, 77.83; H, 6.02; N, 7.32.
4-Bromo-2-(4-methylbenzoyl)pyrrole (3). Following a pro-
cedure for bromination of acyldipyrromethanes,8 a solution of 2
(1.5 g, 8.1 mmol) in dry THF (32 mL) at -78 °C under argon was
treated portionwise with NBS (1.4 g, 8.1 mmol). The reaction
mixture was stirred for 1 h at -78 °C. Hexanes was added to the
reaction mixture at -20 °C. The reaction mixture was then allowed
to warm to 0 °C. Ethyl acetate was added. The organic layer was
washed with water, dried (Na2SO4), and concentrated. The resulting
brown solid was purified by column chromatography [silica,
hexanes/CH2Cl2/ethyl acetate (9:0.5:0.5 then 7:2:1)] to afford a
Zn(II)-7-Bromo-17,18-dihydro-18,18-dimethyl-10-p-tolylpor-
phyrin (ZnC-Br7T10) from 5 + 6. Following a streamlined
procedure,10 a solution of 5 (201 mg, 0.412 mmol) and 6
(90.0 mg, 0.412 mmol) in anhydrous CH2Cl2 (12 mL) was treated
with a solution of p-TsOH‚H2O (392 mg, 2.06 mmol) in anhydrous
methanol (3 mL) under argon. The resulting red reaction mixture
was stirred at room temperature for 50 min. A sample of 2,2,6,6-
tetramethylpiperidine (0.700 mL, 4.12 mmol) was added. The
reaction mixture was concentrated. The resulting solid was dissolved
in CH3CN (41 mL) and subsequently treated with 2,2,6,6-tetra-
methylpiperidine (1.75 mL, 10.3 mmol), Zn(OAc)2 (1.13 g, 6.18
mmol), and AgOTf (318 mg, 1.24 mmol). The resulting suspension
was refluxed for 20 h exposed to air. The crude mixture was filtered
through a pad of silica (CH2Cl2). The filtrate was chromatographed
[silica, hexanes then hexanes/CH2Cl2 (1:2)] to afford a green solid
(17.8 mg, 7.6%): 1H NMR δ 1.99 (s, 6H), 2.67 (s, 3H), 4.46 (s,
2H), 7.49 (d, J ) 7.6 Hz, 2H), 7.90 (d, J ) 7.6 Hz, 2H), 8.49 (s,
1H), 8.53 (s, 1H), 8.56 (d, J ) 4.4 Hz, 1H), 8.61 (s, 1H), 8.65 (d,
J ) 4.4 Hz, 1H), 8.67 (d, J ) 4.4 Hz, 1H), 9.00 (d, J ) 4.4 Hz,
1H), 9.61 (s, 1H); LD-MS obsd 570.2; FAB-MS obsd 570.0416,
calcd 570.0398 (C29H23BrN4Zn); λabs 410, 603 nm.
Zn(II)-7-Bromo-17,18-dihydro-18,18-dimethyl-10-p-tolylpor-
phyrin (ZnC-Br7T10) from 7 + 6. Following a streamlined
procedure,10 a solution of 7 (90.0 mg, 0.285 mmol) in dry THF
(3.0 mL) at -78 °C under argon was treated portionwise with NBS
(51.0 mg, 0.285 mmol). The reaction mixture was stirred for 1 h at
-78 °C. The cooling bath was removed, and the reaction mixture
was then allowed to warm to 0 °C. Hexanes was added, and the
minimum amount of ethyl acetate was used to transfer the reaction
mixture to a separatory funnel. The mixture was washed with ice-
cold water. The organic layer was separated, dried (K2CO3), and
concentrated. (Note: All of the workup operations including solvent
removal should be done without heating, and preferably under
chilled conditions.) The resulting crude dibromodipyrromethane (7-
R-Br) was dissolved in anhydrous CH2Cl2 (4.0 mL), whereupon
compound 6 (62.2 mg, 0.285 mmol) was added. The solution was
treated with a solution of p-TsOH‚H2O (271 g, 1.42 mmol) in
anhydrous methanol (1.0 mL) under argon. The resulting red
reaction mixture was stirred at room temperature for 40 min. A
sample of 2,2,6,6-tetramethylpiperidine (0.607 mL, 3.55 mmol) was
added. The reaction mixture was concentrated. The resulting yellow
solid was dissolved in CH3CN (28.5 mL) and subsequently treated
with 2,2,6,6-tetramethylpiperidine (1.22 mL, 7.12 mmol), Zn(OAc)2
(784 mg, 4.27 mmol), and AgOTf (220 mg, 0.855 mmol). The
resulting suspension was refluxed for 14 h exposed to air. The crude
mixture was filtered through a pad of silica (CH2Cl2). The filtrate
was chromatographed [silica, hexanes/CH2Cl2 (2:1f1:1f1:2)] to
afford a green solid (68.2 mg, 41%): 1H NMR δ 1.99 (s, 6H),
2.67 (s, 3H), 4.46 (s, 2H), 7.49 (d, J ) 7.6 Hz, 2H), 7.90 (d, J )
7.6 Hz, 2H), 8.49 (s, 1H), 8.53 (s, 1H), 8.56 (d, J ) 4.4 Hz, 1H),
8.61 (s, 1H), 8.65 (d, J ) 4.4 Hz, 1H), 8.67 (d, J ) 4.4 Hz, 1H),
9.00 (d, J ) 4.4 Hz, 1H), 9.61 (s, 1H); 13C NMR δ 21.7, 31.1,
45.5, 50.4, 94.7, 97.4, 106.9, 116.5, 123.6, 127.2, 127.7, 127.9,
129.6, 133.7, 133.8, 133.9, 137.4, 139.0, 142.8, 145.9, 146.3, 146.4,
153.8, 154.7, 160.0, 171.8; LD-MS obsd 570.2; FAB-MS obsd
570.0416, calcd 570.0398 (C29H23BrN4Zn); λabs 410, 603 nm.
7-Bromo-17,18-dihydro-18,18-dimethyl-10-p-tolylporphyrin
(FbC-Br7T10). A solution of ZnC-Br7T10 (9.60 mg, 0.0167 mmol)
in CH2Cl2 (1.0 mL) was treated dropwise with TFA (40.0 µL,
0.485 mmol) over a 2 min period. The solution was stirred at room
temperature for 3 h. CH2Cl2 was added. The mixture was washed
with saturated aqueous NaHCO3, water, and brine. The organic layer
was separated, dried (Na2SO4), and concentrated. The resulting
residue was chromatographed [silica, hexanes then hexanes/CH2-
Cl2 (1:1)] to afford a greenish-purple solid (7.3 mg, 87%): 1H NMR
δ -2.25 (br s, 1H), -1.94 (br s, 1H), 2.05 (s, 6H), 2.69 (s, 3H),
4.61 (s, 2H), 7.54 (d, J ) 7.6 Hz, 2H), 8.00 (d, J ) 7.6 Hz, 2H),
8.66 (s, 1H), 8.78-8.82 (m, 2H), 8.89 (s, 1H), 8.94 (dd, J ) 4.4,
2.0 Hz, 1H), 9.00 (s, 1H), 9.27 (dd, J ) 4.4, 2.0 Hz, 1H), 10.02 (s,
1
yellow solid (1.32 g, 62%): mp 172-174 °C (dec); H NMR δ
2.34 (s, 3H), 6.85-6.91 (m, 1H), 7.09-7.19 (m, 1H), 7.29 (d, J )
8.2 Hz, 2H), 7.79 (d, J ) 8.2 Hz, 2H), 9.62 (br s, 1H); 13C NMR
δ 21.8, 98.4, 120.4, 124.9, 129.3, 129.4, 131.2, 135.0, 143.3, 184.2.
Anal. Calcd for C12H10BrNO: C, 54.57; H, 3.82; N, 5.30. Found:
C, 54.53; H, 3.77; N, 5.24.
2-Bromo-9-decylthio-5-p-tolyldipyrromethane (5). A solution
of 3 (305 mg, 1.15 mmol) in dry THF/methanol (22 mL, 10:1) at
0 °C was treated with NaBH4 (655 mg, 17.2 mmol). The mixture
was stirred for 2 h. Water was added, and the resulting mixture
was extracted with ethyl acetate. The organic layer was separated,
dried (Na2SO4), and concentrated to dryness. The resulting residue
was dissolved in toluene (11.6 mL), whereupon decylthiopyrrole 4
(246 mg, 1.15 mmol) was added. The solution was treated with
InCl3 (25.4 mg, 0.115 mmol) at room temperature. The reaction
was monitored by TLC [silica, hexanes/ethyl acetate (3:1)]. After
30 min, the reaction mixture was quenched by addition of 1 M
NaOH. The resulting mixture extracted with CH2Cl2. The organic
layer was separated, washed with water, dried (Na2SO4), and
concentrated. The resulting residue was purified by column
chromatography [silica, hexanes/CH2Cl2/ethyl acetate (9.5:0.25:0.25
then 9.0:0.5:0.5)] to afford a yellow oil (469 mg, 83%): 1H NMR
δ 0.88 (t, J ) 7.2 Hz, 3H), 1.25-1.32 (m, 14H), 1.46-1.52 (m,
2H), 2.34 (s, 2H), 2.58 (t, J ) 7.2 Hz, 2H), 5.33 (s, 1H), 5.88-
5.88 (m, 1H), 5.89-5.93 (m, 1H), 6.25-6.28 (m, 1H), 6.67-6.68
(m, 1H), 7.06 (d, J ) 8.2 Hz, 2H), 7.14 (d, J ) 8.2 Hz, 2H), 7.85
(br s, 2H); 13C NMR δ 14.3, 21.2, 22.8, 28.6, 29.4, 29.5, 29.7,
29.8, 30.1, 32.1, 38.2, 43.9, 96.4, 109.3, 110.1, 116.9, 117.2, 119.4,
128.2, 128.4, 129.6, 129.7, 133.3, 134.4, 137.3, 137.8. Anal. Calcd
for C26H35BrN2S: C, 64.05; H, 7.24; N, 5.75. Found: C, 64.14;
H, 7.44; N, 5.62.
2-Bromo-5-p-tolyldipyrromethane (7).
A solution of 3
(178 mg, 0.674 mmol) in dry THF/methanol (11 mL, 10:1) at 0 °C
was treated with NaBH4 (383 mg, 10.1 mmol). The mixture was
stirred for 2 h. Water was added, and the resulting mixture was
extracted with ethyl acetate. The organic layer was separated, dried
(Na2SO4), and concentrated. The resulting crude solid was dissolved
in 1,4-dioxane (8.5 mL), whereupon pyrrole (748 µL, 10.7 mmol)
was added. The solution was treated with 10% aqueous HCl
(850 µL), and the mixture was stirred for 15-20 min at room
temperature. The formation of dipyrromethane was monitored by
TLC [silica, hexanes/ethyl acetate (3:1)]. After 20 min, the reaction
mixture was diluted with ethyl acetate. Saturated aqueous NaHCO3
was added. The mixture was washed with water. The organic layer
was separated, dried (K2CO3), and concentrated. The resulting
residue was purified by column chromatography [silica, hexanes/
CH2Cl2/ethyl acetate (9:0.5:0.5 then 8:1:1)] to afford a brown oil
(112 mg, 52%): 1H NMR (THF-d8) δ 2.28 (s, 3H), 5.28 (s, 1H),
5.64-5.66 (m, 2H), 5.92-5.94 (m, 1H), 6.58-6.62 (m, 2H), 7.05
(s, 4H), 9.74 (br s, 1H), 10.00 (br s, 1H); 13C NMR (THF-d8) δ
21.2, 44.9, 95.7, 107.8, 108.1, 110.3, 117.9, 118.0, 129.3, 129.6,
133.4, 135.8, 136.7, 141.0; FAB-MS obsd 314.0432, calcd 314.0419
(C16H15BrN2). Note: Careful handling of the solution of compound
7 is required. All of the workup operations including solvent
removal should be done without heating, and preferably under
chilled conditions.
J. Org. Chem, Vol. 72, No. 20, 2007 7745

Muthiah et al.
1H); 13C NMR (75 MHz) δ 21.7, 31.3, 46.7, 52.1, 94.6, 97.3, 104.8,
120.6, 121.7, 123.8, 123.9, 127.9, 129.1, 129.3, 132.4, 134.1, 134.5,
135.4, 137.7, 138.4, 140.1, 141.6, 146.8, 150.5, 163.6, 176.1; LD-
MS obsd 508.9; FAB-MS obsd 508.1257, calcd 508.1263 (C29H25-
BrN4); λabs 408, 634 nm.
2H), 7.50 (d, J ) 7.6 Hz, 2H), 7.93 (d, J ) 7.6 Hz, 2H), 8.46 (s,
1H), 8.53 (d, J ) 4.4 Hz, 1H), 8.56 (s, 1H), 8.58 (s, 1H), 8.63 (d,
J ) 4.4 Hz, 1H), 8.65 (d, J ) 4.4 Hz, 1H), 8.96 (d, J ) 4.4 Hz,
1H), 9.76 (s, 1H); 13C NMR δ 11.9, 18.8, 19.2, 21.7, 31.0, 45.5,
50.3, 94.4, 97.2, 97.6, 103.1, 107.1, 122.0, 124.4, 127.0, 127.7,
127.8, 131.4, 133.7, 133.8, 137.3, 139.2, 145.8, 146.46, 146.49,
147.6, 153.9, 155.0, 159.8, 171.9; LD-MS obsd 672.7; FAB-MS
7-Acetyl-17,18-dihydro-18,18-dimethyl-10-p-tolylporphyrin
(FbC-A7T10). Following a procedure for Stille coupling with
chlorins,9 a mixture of FbC-Br7T10 (8.20 mg, 0.0161 mmol),
tributyl(1-ethoxyvinyl)tin (22 µL, 0.064 mmol), and (PPh3)2PdCl2
(2.26 mg, 0.00322 mmol) was refluxed in THF (1.5 mL) for 18 h
in a Schlenk line. The reaction mixture was treated with 10%
aqueous HCl (0.5 mL) at room temperature for 2 h. CH2Cl2 was
added, and the organic layer was separated. The organic layer was
washed with saturated aqueous NaHCO3, water, and brine. The
organic layer was dried (Na2SO4), concentrated, and chromato-
graphed [silica, hexanes/CH2Cl2 (1:1)] to afford a purple solid (5.3
mg, 69%): 1H NMR (THF-d8) δ -1.77 (br s, 1H), -1.41 (br s,
1H), 2.03 (s, 6H), 2.68 (s, 3H), 2.92 (s, 3H), 4.58 (s, 2H), 7.58 (d,
J ) 7.6 Hz, 2H), 8.01 (d, J ) 7.6 Hz, 2H), 8.72 (d, J ) 4.4 Hz,
1H), 8.80 (d, J ) 4.4 Hz, 1H), 8.92 (s, 1H), 8.42-8.43 (s, 1H +
d, 1H, overlapped), 9.04 (s, 1H), 9.33 (d, J ) 4.4 Hz, 1H), 10.96
(s, 1H); 13C NMR δ 21.7, 30.0, 31.1, 46.7, 51.8, 94.2, 96.9, 109.3,
109.4, 123.81, 123.85, 124.3, 127.9, 129.6, 131.3, 134.1, 135.4,
135.9, 137.8, 138.3, 138.4, 141.2, 143.1, 147.9, 148.0, 164.4, 177.5,
197.6; LD-MS obsd 472.1; FAB-MS obsd 472.2275, calcd 472.2263
(C31H28N4O); λabs 420, 634 nm.
13-Acetyl-17,18-dihydro-18,18-dimethyl-10-p-tolylporphy-
rin (FbC-A7T10). A solution of ZnC-Br7T10 (17.5 mg, 0.0305
mmol) in CH2Cl2 (2.0 mL) was treated dropwise with TFA
(71 µL, 0.92 mmol). The solution was stirred at room temperature
for 3 h. CH2Cl2 was added, and the organic layer was washed with
saturated aqueous NaHCO3, water, and brine. The organic layer
was separated, dried (Na2SO4), and concentrated. The resulting
crude solid was used in the next step. Following a procedure for
Stille coupling,9 a mixture composed of the crude sample of FbC-
Br7T10, tributyl(1-ethoxyvinyl)tin (41.2 µL, 0.122 mmol), and
(PPh3)2PdCl2 (4.30 mg, 0.00610 mmol) was refluxed in THF (2.0
mL) for 18 h in a Schlenk line. The reaction mixture was treated
with 10% aqueous HCl (1.1 mL) at room temperature for 2 h. CH2-
Cl2 was added, and the organic layer was separated. The organic
layer was washed (saturated aqueous NaHCO3, water, and brine),
dried (Na2SO4), and concentrated. The residue was chromato-
graphed [silica, hexanes/CH2Cl2 (1:1)] to afford a purple solid (9.6
mg, 66%). The characterization data (1H NMR, LD-MS, FAB-MS,
UV-vis) were consistent with those for the product obtained as
described in the stepwise procedure.
Zn(II)-7-Acetyl-17,18-dihydro-18,18-dimethyl-10-p-tolylpor-
phyrin (ZnC-A7T10). A solution of FbC-A7T10 (3.2 mg, 0.0068
mmol) in CHCl3 (2.0 mL) was treated with a solution of Zn(OAc)2‚
2H2O (22.3 mg, 0.101 mmol) in methanol (0.5 mL). The reaction
mixture was stirred at room temperature for 16 h. The crude mixture
was concentrated and chromatographed (silica, CH2Cl2) to afford
a green solid (3.2 mg, 88%): 1H NMR δ 2.02 (s, 6H), 2.65 (s,
3H), 3.05 (s, 3H), 4.52 (s, 2H), 7.55 (d, J ) 7.6 Hz, 2H), 8.00 (d,
J ) 7.6 Hz, 2H), 8.69 (d, J ) 4.4 Hz, 1H), 8.72-8.74 (s, 1H + d,
1H, overlapped), 8.84-8.85 (s, 1H + d, 1H, overlapped), 9.04 (s,
1H), 9.26 (d, J ) 4.4 Hz, 1H), 10.92 (s, 1H); LD-MS obsd 534.2;
FAB-MS obsd 534.1392, calcd 534.1398 (C31H26N4OZn); λabs 426,
598 nm.
Zn(II)-17,18-Dihydro-18,18-dimethyl-10-p-tolyl-7-[2-(triiso-
propylsilyl)ethynyl]porphyrin (ZnC-E7T10). Following a general
procedure,9 samples of ZnC-Br7T10 (20.1 mg, 0.0351 mmol) and
triisopropylsilylacetylene (23.4 µL, 0.105 mmol) were coupled using
Pd2(dba)3 (6.43 mg, 0.00702 mmol) and P(o-tol)3 (13.8 mg, 0.0456
mmol) in toluene/TEA (5:1, 15 mL) at 60 °C under argon. After
22 h, the reaction mixture was concentrated under reduced pressure.
The resulting residue was chromatographed [silica, hexanes then
hexanes/CH2Cl2 (1:1)] to afford a green solid (18.1 mg, 76%): 1H
NMR δ 1.35-1.38 (m, 21H), 1.99 (s, 6H), 2.68 (s, 3H), 4.45 (s,
obsd 672.2626, calcd 672.2627 (C40H44N4SiZn); λabs 421, 605 nm.
17,18-Dihydro-18,18-dimethyl-10-p-tolyl-7-[2-(triisopropylsi-
lyl)ethynyl]porphyrin (FbC-E7T10). A solution of ZnC-E7T10
(8.20 mg, 0.0122 mmol) in CH2Cl2 (1.0 mL) was treated dropwise
with TFA (28.0 µL, 0.366 mmol) over a 2 min period. The solution
was stirred at room temperature for 3 h. CH2Cl2 was added, and
the organic layer was washed (saturated aqueous NaHCO3 and
water), dried (Na2SO4), and concentrated. The resulting solid was
chromatographed [silica, hexanes then hexanes/CH2Cl2 (4:1)] to
afford a green solid (6.1 mg, 82%): 1H NMR δ -2.11 (br s, 1H),
-1.71 (br s, 1H), 1.25-1.38 (m, 21H), 2.06 (s, 6H), 2.68 (s, 3H),
4.61 (s, 2H), 7.53 (d, J ) 7.6 Hz, 2H), 8.00 (d, J ) 7.6 Hz, 2H),
8.71 (s, 1H), 8.76-8.78 (m, 2H), 8.84 (s, 1H), 8.92 (d, J ) 4.4
Hz, 1H), 8.97 (s, 1H), 9.21 (d, J ) 4.4 Hz, 1H), 10.1 (s, 1H); LD-
MS obsd 610.1; FAB-MS obsd 610.3496, calcd 610.3492 (C40H46N4-
Si); λabs 415, 639 nm.
Zn(II)-7-Formyl-17,18-dihydro-18,18-dimethyl-10-p-tolylpor-
phyrin (ZnC-F7T10). Following a procedure for CO-mediated
formylation,12 a mixture of ZnC-Br7T10 (12.1 mg, 0.0211 mmol),
(PPh3)2PdCl2 (3.00 mg, 0.00422 mmol, 20 mol %), PPh3 (1.10 mg,
0.00422 mmol, 20 mol %), and sodium formate (3.60 mg, 0.0527
mmol) was dried in a Schlenk flask for 1 h. DMF (1.6 mL) was
added, and CO gas was bubbled through the reaction mixture for
2 h. Then, the reaction mixture was heated at 108 °C under a balloon
containing CO for 24 h. The reaction mixture was allowed to cool
to room temperature. The reaction mixture was treated with CH2-
Cl2 and water. The organic layer was separated, washed (water,
brine), dried (Na2SO4), and concentrated. The resulting solid was
chromatographed [silica, hexanes f hexanes/CH2Cl2 (1:2) f CH2-
Cl2] to afford the starting chlorin (32%) followed by the title
compound as a green solid (4.1 mg, 37%): 1H NMR δ 1.99 (s,
6H), 2.65 (s, 3H), 4.41 (s, 2H), 7.50 (d, J ) 7.6 Hz, 2H), 7.90 (d,
J ) 7.6 Hz, 2H), 8.40-8.46 (m, 3H), 8.46 (d, J ) 4.4 Hz, 1H),
8.61 (d, J ) 4.4 Hz, 1H), 8.75 (s, 1H), 8.98 (d, J ) 4.4 Hz, 1H),
10.23 (s, 1H), 10.95 (s, 1H); 13C NMR δ 21.6, 30.8, 31.1, 46.3,
50.9, 94.2, 97.3, 109.4, 128.1, 128.2, 129.6, 134.4, 134.5, 135.3,
135.5, 135.9, 138.0, 140.8, 144.5, 144.9, 147.5, 148.6, 149.4, 156.1,
157.6, 161.2, 174.0, 188.1; LD-MS obsd 520.1; FAB-MS obsd
520.1251, calcd 520.1242 (C30H24N4OZn); λabs 428, 598 nm.
1-Formyl-5-p-tolyldipyrromethane (9a). Following a procedure
for the formylation of dipyrromethanes,16 a sample of 8a (2.36 g,
10.0 mmol) in THF (20 mL) was treated with MesMgBr (20 mL,
1.0 M in THF). After 15 min, the reaction mixture was cooled to
-78 °C. Phenyl formate was added (2.18 mL) in one portion. The
reaction mixture was stirred at -78 °C for 1 h. The cooling bath
was removed, and stirring was continued for 1 h. The reaction
mixture was quenched by the addition of saturated aqueous NH4-
Cl. The resulting mixture was extracted with CH2Cl2. The organic
layer was washed (water, brine) and concentrated. The resulting
dark oil was dissolved in CH3CN (40 mL) and treated with 2 M
aqueous NaOH (40 mL). The resulting mixture was stirred
vigorously at room temperature for 1 h. Water was added, and the
mixture was extracted with CH2Cl2. The organic phase was washed
(saturated aqueous NH4Cl, water, brine), dried (Na2SO4), and
concentrated. The resulting residue was chromatographed [silica,
hexanes then CH2Cl2/ethyl acetate (9:1)] to afford a yellow solid
1
(0.958 g, 36%): mp 181-183 °C (dec); H NMR δ 2.33 (s, 3H),
5.48 (s, 1H), 5.94-5.96 (m, 1H), 6.85-6.12 (m, 1H), 6.14-6.17
(m, 1H), 6.68-6.71 (m, 1H), 6.88-6.90 (m, 1H), 7.05 (d, J ) 8.2
Hz, 2H), 7.12 (d, J ) 8.2 Hz, 2H), 8.12 (br s, 1H), 9.30 (s, 1H),
9.44 (br s, 1H); 13C NMR δ 21.2, 43.9, 107.9, 108.8, 110.9, 118.0,
7746 J. Org. Chem., Vol. 72, No. 20, 2007

Two Complementary Routes to 7-Substituted Chlorins
122.4, 128.4, 129.8, 130.8, 132.4, 137.4, 137.5, 143.0, 178.8; FAB-
MS obsd 264.1265, calcd 264.1263 (C17H16N2O).
15-Bromo-17,18-dihydro-18,18-dimethyl-10-p-tolylporphy-
rin (FbC-T10Br15). A solution of FbC-T10 (57.1 mg, 0.132 mmol)
in THF (65 mL) was treated with NBS (23.6 mg, 0.132 mmol).
The resulting mixture was stirred for 1 h. The reaction mixture
was diluted with CH2Cl2 (∼50 mL) and quenched by addition of
saturated aqueous NaHCO3. The organic layer was separated, dried
(Na2SO4), and concentrated. Column chromatography of the result-
ing solid [silica, hexanes f hexanes/CH2Cl2 (1:1)] provided a trace
amount of unidentified dibromochlorin (first fraction) followed by
the title compound as a purple solid (41.2 mg, 61%): 1H NMR δ
-2.10 (br s, 1H), -1.94 (br s, 1H), 2.06 (s, 6H), 2.69 (s, 3H), 4.69
(s, 2H), 7.53 (d, J ) 7.6 Hz, 2H), 8.00 (d, J ) 7.6 Hz, 2H), 8.61
(d, J ) 4.4 Hz, 1H), 8.76 (d, J ) 4.4 Hz, 1H), 8.83 (s, 1H), 8.88
(d, J ) 4.4 Hz, 1H), 8.92 (d, J ) 4.4 Hz, 1H), 9.19 (d, J ) 4.4 Hz,
1H), 9.20 (d, J ) 4.4 Hz, 1H), 9.73 (s, 1H); LD-MS obsd 508.9;
FAB-MS obsd 508.1257, calcd 508.1263 (C29H25BrN4); λabs 404,
642 nm.
1-Formyl-5-pentyldipyrromethane (9b). A sample of DMF
(10 mL) was treated with POCl3 (1.50 mL, 16.4 mmol) at 0 °C.
The resulting mixture was stirred at 0 °C for 10 min (Vilsmeier
reagent). A solution of 8b (2.00 g, 9.25 mmol) in anhydrous DMF
(30 mL) was treated with the freshly prepared Vilsmeier reagent
(6.97 mL, 11.4 mmol) at 0 °C. The resulting mixture was stirred at
0 °C for 1.5 h. The reaction mixture was poured slowly into an
ice-cooled mixture of CH2Cl2 (50 mL) and 2 M aqueous NaOH
(50 mL). The resulting mixture was stirred for 20 min, the organic
layer was separated, and the water phase was extracted with CH2-
Cl2. The combined organic extract was washed (aqueous NH4Cl,
water, and brine), dried (Na2SO4), and concentrated. Column
chromatography [silica, CH2Cl2 f CH2Cl2/ethyl acetate (5:1)]
afforded a light-pink solid (0.632 g, 28%): mp 82-84 °C; 1H NMR
δ 0.83-0.87 (m, 3H), 1.24-1.31 (m, 6H), 2.03-2.05 (m, 2H),
4.07-4.10 (m, 1H), 6.04-6.05 (m, 1H), 6.12-6.14 (m, 1H), 6.18-
6.20 (m, 1H), 6.68-6.70 (m, 1H), 6.95-6.96 (m, 1H), 8.78 (br s,
1H), 9.35 (s, 1H), 10.28 (br s, 1H); 13C NMR δ 14.2, 22.6, 27.6,
31.8, 33.9, 38.4, 105.4, 108.2, 109.6, 117.5, 124.8, 132.0, 132.3,
146.9, 178.8. Anal. Calcd for C15H20N2O: C, 73.74; H, 8.25; N,
11.47. Found: C, 73.58; H, 8.26; N, 11.38.
Zn(II)-17,18-Dihydro-18,18-dimethyl-10-p-tolylporphyrin (ZnC-
T10). Following a streamlined procedure,10 a solution of 9a
(310 mg, 1.17 mmol) in dry THF (12 mL) at -78 °C under argon
was treated portionwise with NBS (209 mg, 1.17 mmol). The
reaction mixture was stirred for 1 h at -78 °C. The cooling bath
was removed, and the reaction mixture was allowed to warm to
0 °C. Ethyl acetate was added. The organic layer was washed with
water, dried (Na2SO4), and concentrated. The resulting crude
bromoformyldipyrromethane was used in the next reaction. The
crude product was dissolved in anhydrous CH2Cl2 (32 mL),
whereupon 10 (223 mg, 1.17 mmol) was added. The solution was
treated with a solution of p-TsOH‚H2O (1.11 g, 5.87 mmol) in
anhydrous methanol (8 mL) under argon. The resulting red reaction
mixture was stirred at room temperature for 50 min. A sample of
2,2,6,6-tetramethylpiperidine (1.98 mL, 11.7 mmol) was added. The
reaction mixture was concentrated. The resulting solid was dissolved
in CH3CN (117 mL) and subsequently treated with 2,2,6,6-
tetramethylpiperidine (4.96 mL, 29.2 mmol), Zn(OAc)2 (3.22 g,
17.5 mmol), and AgOTf (902 mg, 3.51 mmol). The resulting
suspension was refluxed for 18 h exposed to air. The crude mixture
was filtered through a pad of silica (CH2Cl2). The filtrate was
chromatographed [silica, hexanes/CH2Cl2 (1:2)] to afford a green
solid (212 mg, 37%): 1H NMR (THF-d8) δ 2.04 (s, 6H), 2.67 (s,
3H), 4.54 (s, 2H), 7.50 (d, J ) 7.6 Hz, 2H), 7.95 (d, J ) 7.6 Hz,
2H), 8.43 (d, J ) 4.4 Hz, 1H), 8.57-8.63 (m, 4H), 8.73 (d, J )
4.4 Hz, 1H), 8.79 (d, J ) 4.4 Hz, 1H), 9.04 (d, J ) 4.4 Hz, 1H),
9.60 (s, 1H); 13C NMR δ 21.7, 31.0, 45.4, 50.3, 94.2, 97.0, 109.4,
124.0, 126.7, 127.2, 127.6, 128.1, 129.2, 132.9, 133.3, 133.8, 137.1,
139.6, 145.8, 146.1, 146.4, 147.6, 153.1, 154.0, 159.1, 171.0; LD-
MS obsd 492.3; FAB-MS obsd 492.1302, calcd 492.1292 (C29H24N4-
Zn); λabs 405, 605 nm.
Zn(II)-17,18-Dihydro-18,18-dimethyl-10-pentylporphyrin (ZnC-
Pn10). A solution of 9b (0.244 g, 1.00 mmol) in THF (10 mL) was
treated with NBS (0.178 g, 1.00 mmol) at -78 °C. The resulting
mixture was stirred at -78 °C for 1 h, brought to ∼ -20 °C, and
quenched by addition of hexanes/water (40 mL, 1:1). The resulting
mixture was extracted with ethyl acetate. The organic extract was
washed with water and brine, dried (Na2SO4), and concentrated to
afford the crude 1-bromo-9-formyl-5-pentyldipyrromethane
(0.302 g, 93%), which was used in the next step without further
purification. A solution of crude 1-bromo-9-formyl-5-pentyldipyr-
romethane (0.162 g, 0.500 mmol) and Western half 10 (0.095 g,
0.50 mmol) in CH2Cl2 (10.8 mL) was treated with a solution of
p-TsOH‚H2O (0.475 g, 2.50 mmol) in MeOH (8.25 mL) at room
temperature. The resulting mixture was stirred at room temperature
for 30 min, quenched by addition of 2,2,6,6-tetramethylpiperidine
(0.630 mL, 3.71 mmol), and concentrated. The resulting yellow-
brown solid was dissolved in CH3CN (50 mL) and treated with
2,2,6,6-tetramethylpiperidine (2.10 mL, 12.4 mmol), Zn(OAc)2
(1.37 g, 7.50 mmol), and AgOTf (0.385 g, 1.50 mmol). The
resulting mixture was refluxed for 24 h and concentrated. The
resulting black residue was chromatographed [silica, hexanes/CH2-
Cl2 (1:1)]. The green-violet fraction was collected and rechromato-
graphed with protection from light [silica, hexanes/CH2Cl2/Et3N
(50:50:1)] to afford a green solid (61 mg, 26%). ZnC-Pn10 is rather
unstable in solution and during routine handling. It is recommended
to carry out the demetalation reaction immediately after purification
of the Zn(II) complex. By contrast, FbC-Pn10 is much more stable.
Data for the title compound: 1H NMR (300 MHz) δ 0.97 (t, J )
7.4 Hz, 3H), 1.44-1.57 (m, 2H), 1.67-1.77 (m, 2H), 1.99 (s, 6H),
2.32-2.42 (m, 2H), 4.43 (s, 2H), 4.51-4.56 (m, 2H), 8.47 (s, 1H),
8.51 (s, 1H), 8.56 (d, J ) 4.2 Hz, 1H), 8.66 (d, J ) 4.2 Hz, 1H),
8.75 (d, J ) 4.2 Hz, 1H), 8.96 (d, J ) 4.2 Hz, 1H), 8.98 (d, J )
4.2 Hz, 1H), 9.19 (d, J ) 4.2 Hz, 1H), 9.39 (s, 1H); 13C NMR δ
14.14, 23.0, 31.1, 33.1, 35.3, 37.7, 45.5, 50.3, 93.9, 96.6, 109.3,
124.6, 126.0, 126.8, 127.3, 128.3, 130.1, 133.1, 145.8, 145.9, 146.1,
147.4, 152.8, 154.4, 158.7, 171.2; LD-MS obsd 472.4; FAB-MS
obsd 472.1600, calcd 472.1605 (C27H28N4Zn); λabs 405, 604 nm.
17,18-Dihydro-18,18-dimethyl-10-pentylporphyrin (FbC-
Pn10). Following a reported procedure,11 a sample of ZnC-Pn10
(80 mg, 0.17 mmol) in CH2Cl2 (70 mL) was treated with TFA
(1.30 mL). The resulting mixture was stirred at room temperature
for 1 h and then neutralized by addition of excess Et3N (5 mL).
The resulting mixture was concentrated and chromatographed
[silica, hexanes/CH2Cl2 (1:1)] to afford a green solid (57 mg,
81%): 1H NMR δ -2.19 (br s, 1H), -1.76 (br s, 1H), 0.95 (t, J )
7.2 Hz, 3H), 1.47-1.56 (m, 2H), 1.70-1.77 (m, 2H), 2.01 (s, 6H),
2.42-2.50 (m, 2H), 4.56 (s, 2H), 4.76-4.78 (m, 2H), 8.81 (s, 1H),
8.82-8.83 (m, 1H), 8.86-8.87 (m, 1H), 8.91 (s, 1H), 9.01 (d, J )
4.4 Hz, 1H), 9.15-9.16 (m, 1H), 9.24 (d, J ) 4.4 Hz, 1H), 9.34-
9.35 (m, 1H), 9.75 (s, 1H); 13C NMR δ 14.4, 23.0, 31.3, 33.0, 34.9,
37.9, 46.5, 52.0, 93.8, 96.5, 107.1, 122.5, 123.1, 123.6, 125.4, 128.5,
129.1, 132.9, 133.9, 135.4, 139.3, 141.4, 150.2, 153.0, 162.4, 175.6;
17,18-Dihydro-18,18-dimethyl-10-p-tolylporphyrin (FbC-T10).
A solution of ZnC-T10 (65.3 mg, 0.133 mmol) in CH2Cl2 (3.5 mL)
was treated dropwise with TFA (307 µL, 3.99 mmol) over a 3 min
period. The solution was stirred at room temperature for 3 h. CH2-
Cl2 was added, and the organic layer was washed (saturated aqueous
NaHCO3 and water) and then dried (Na2SO4). The organic layer
was concentrated and chromatographed [silica, hexanes then
hexanes/CH2Cl2 (1:1)] to afford a purple solid (52.3 mg, 92%):
1H NMR (300 MHz) δ -2.30 (br s, 1H), -1.92 (br s, 1H), 2.07 (s,
6H), 2.69 (s, 3H), 4.65 (s, 2H), 7.54 (d, J ) 7.6 Hz, 2H), 8.04 (d,
J ) 7.6 Hz, 2H), 8.67 (d, J ) 4.4 Hz, 1H), 8.83 (br s, 2H), 8.90 (s,
1H), 8.96 (d, J ) 4.4 Hz, 1H), 8.98 (d, J ) 4.4 Hz, 1H), 9.03 (s,
1H), 9.24 (d, J ) 4.4 Hz, 1H), 9.86 (s, 1H); LD-MS obsd 430.6;
FAB-MS obsd 431.2222, calcd 431.2236 [(M + H)+, M )
C29H26N4]; λabs 405, 635 nm.
J. Org. Chem, Vol. 72, No. 20, 2007 7747

Muthiah et al.
LD-MS obsd 410.1; FAB-MS obsd 411.2547, calcd 411.2543 [(M
+ H)+, M ) C27H30N4]; λabs 394, 636 nm.
147.8, 150.4, 160.2, 176.1; LD-MS obsd 506.3; FAB-MS obsd
506.2462, calcd 506.2470 (C35H30N4); λabs 410, 641 nm.
15-Bromo-17,18-dihydro-18,18-dimethyl-10-pentylporphy-
rin (FbC-Pn10Br15). A solution of FbC-Pn10 (69.4 mg, 0.169
mmol) in THF (85 mL) was treated with NBS (1.69 mL, 0.100 M
in THF). The resulting reaction mixture was stirred at room
temperature for 1 h. The reaction mixture was diluted with CH2-
Cl2 (∼100 mL) and quenched by addition of saturated aqueous
NaHCO3. The organic layer was separated, and the aqueous phase
was extracted with CH2Cl2. The organic extract was washed with
water and brine, dried (Na2SO4), and concentrated. Column
chromatography (silica, hexanes/CH2Cl2 (5:2)] provided an uni-
dentified dibromochlorin (first fraction, purple-brown) and FbC-
Pn10Br15 (second fraction, purple-brown). Data for the title
compound: purple-brown solid; 44 mg (54%); 1H NMR (300 MHz)
δ -2.19 (br s, 1H), -1.76 (br s, 1H), 0.94-0.99 (m 3H), 1.49-
1.56 (m, 2H), 1.70-1.80 (m, 2H), 2.02 (s, 6H), 2.40-2.48 (m,
2H), 4.64 (s, 2H), 4.75-4.80 (m, 2H), 8.72 (s, 1H), 8.84-8.86
(m, 1H), 8.93 (d, J ) 4.4 Hz, 1H), 9.12-9.13 (m, 1H), 9.23 (d, J
) 4.4 Hz, 1H), 9.25-9.27 (m, 1H), 9.33-9.34 (m, 1H), 9.64 (s,
1H); LD-MS 488.4; FAB-MS obsd 489.1652, calcd 489.1648
(C27H29N4Br); λabs 401, 642 nm.
17,18-Dihydro-18,18-dimethyl-10-pentyl-15-phenylporphy-
rin (FbC-Pn10P15). Samples of FbC-Pn10Br15 (41.9 mg, 0.0856
mmol), 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (176 mg,
0.862 mmol), Pd(PPh3)4 (30.0 mg, 0.026 mmol), and K2CO3 (94
mg, 0.68 mmol) were placed in a Schlenk flask. The flask was
pumped-purged with argon three times. A degassed mixture of
toluene/DMF (3:1, 8.5 mL) was added. The resulting mixture was
stirred at 90-95 °C for 20 h. The reaction mixture was diluted
with CH2Cl2 and filtered. The filtrate was concentrated. The crude
product was dissolved in CH2Cl2 and chromatographed [silica,
hexanes/CH2Cl2 (1:1)] to afford a trace amount of putative PdC-
Pn10P15 (first fraction, blue-violet) and a second fraction (brown).
The latter was concentrated and rechromatographed [silica, hexanes/
CH2Cl2 (2:1)] to afford a brown-violet solid (34 mg, 82%): 1H
NMR δ -2.12 (br s, 1H), -1.96 (br s, 1H), 0.93-0.96 (m, 3H),
1.48-1.53 (m, 2H), 1.71-1.75 (m, 2H), 1.94 (s, 6H), 2.40-2.47
(m, 2H), 4.14 (s, 2H), 4.78-4.82 (m, 2H), 7.70-7.71 (m, 3H),
7.88-7.90 (m, 2H), 8.28 (d, J ) 4.4 Hz, 1H), 8.80 (s, 1H), 8.88
(d, J ) 4.4 Hz, 1H), 9.00 (d, J ) 4.4 Hz, 1H), 9.16 (d, J ) 4.4 Hz,
1H), 9.24 (d, J ) 4.4 Hz, 1H), 9.26 (d, J ) 4.4 Hz, 1H), 9.71 (s,
1H); 13C NMR (75 MHz) δ 14.4, 23.0, 31.4, 33.0, 35.4, 38.0, 46.2,
52.4, 94.1, 106.4, 112.0, 123.5, 123.6, 123.7, 124.7, 127.6, 128.1,
128.3, 129.5, 132.68, 132.73, 134.7, 134.9, 140.1, 141.2, 143.8,
151.1, 152.8, 161.8, 175.6; LD-MS obsd 486.7; FAB-MS obsd
487.2866, calcd 487.2856 [(M + H]+, M ) C33H34N4); λabs 399,
641 nm.
17,18-Dihydro-18,18-dimethyl-10-mesityl-15-phenylporphy-
rin (FbC-M10P15). Samples of FbC-M10Br15 (38.7 mg, 0.0720
mmol), 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (150 mg,
0.735 mmol), Pd(PPh3)4 (25.5 mg, 0.0221 mmol), and K2CO3 (80
mg, 0.58 mmol) were placed in a Schlenk flask. The flask was
pump-purged with argon three times. A degassed mixture of toluene/
DMF (3:1, 7.3 mL) was added. The resulting mixture was stirred
at 90-95 °C for 19 h. The reaction mixture was diluted with CH2-
Cl2 and filtered. The filtrate was concentrated. Column chroma-
tography [silica, hexanes/CH2Cl2 (2:1)] afforded a trace of putative
PdC-M10P15 [first fraction (blue) and a second fraction (green)].
The latter was rechromatographed twice [first column: silica,
hexanes/CH2Cl2 (3:1); second column: silica, hexanes/toluene (1:
2)] to afford a green solid (23.8 mg, 62%): 1H NMR δ -2.10 to
-1.90 (br, 2H), 1.84 (s, 6H), 1.98 (s, 6H), 2.60 (s, 3H), 4.20 (s,
2H), 7.23 (s, 2H), 7.65-7.72 (m, 3H), 7.90-7.92 (m, 2H), 8.21
(d, J ) 4.4 Hz, 1H), 8.44 (d, J ) 4.4 Hz, 1H), 8.50 (d, J ) 4.4 Hz,
1H), 8.88 (d, J ) 4.4 Hz, 1H), 8.90 (s, 1H), 8.94 (d, J ) 4.4 Hz,
1H), 9.20 (d, J ) 4.4 Hz, 1H), 9.76 (s, 1H); 13C NMR (75 MHz)
δ 21.5, 21.7, 31.5, 46.2, 52.4, 94.7, 106.5, 112.2, 120.9, 123.7,
123.9, 126.8, 127.6, 127.8, 128.0, 128.1, 129.0, 131.6, 132.6, 132.7,
134.4, 135.1, 137.6, 138.5, 139.3, 140.4, 140.7, 143.4, 152.0, 152.4,
162.4, 175.2; LD-MS obsd 534.6; FAB-MS obsd 535.2857, calcd
535.2856 (C37H34N4); λabs 411, 640 nm.
7-Bromo-17,18-dihydro-18,18-dimethyl-10-mesityl-15-phe-
nylporphyrin (FbC-Br7M10P15). A solution of FbC-M10P15 (14.5
mg, 0.0271 mmol) in THF (13.5 mL) was treated with NBS (0.270
mL, 0.100 M in THF). The resulting reaction mixture was stirred
at room temperature for 1 h. The reaction mixture was diluted with
CH2Cl2 (∼50 mL) and quenched by addition of saturated aqueous
NaHCO3. The organic layer was separated, and the aqueous phase
was extracted with CH2Cl2. The organic extract was washed with
water and brine, dried (Na2SO4), and concentrated. Column
chromatography [silica, hexanes/CH2Cl2 (2:3)] provided an uni-
dentified dibromochlorin (first fraction, red-brown) and a second
fraction (green-brown). The latter was rechromatographed [silica,
hexanes/CH2Cl2 (2:1)] to afford a brown solid (11 mg, 66%): 1H
NMR δ -2.02 (br s, 1H), -1.92 (br s, 1H), 1.83 (s, 6H), 1.97 (s,
6H), 2.59 (s, 3H), 4.18 (s, 2H), 7.22 (s, 2H), 7.68-7.70 (m, 3H),
7.88-7.89 (m, 2H), 8.19 (d, J ) 4.6 Hz, 1H), 8.43 (s, 1H), 8.48
(d, J ) 4.6 Hz, 1H), 8.88 (s, 1H), 8.93 (d, J ) 4.6 Hz, 1H), 9.23
(d, J ) 4.6 Hz, 1H), 9.92 (s, 1H); 13C NMR δ 21.4, 21.5, 31.4,
46.3, 52.4, 95.0. 104.0, 112.7, 120.9, 121.0, 124.0, 124.3, 127.4,
127.7, 127.9, 128.2, 128.8, 131.6, 132.6, 134.4, 135.5, 137.9, 138.0,
139.3, 141.0, 141.4, 143.2, 148.0, 150.2, 163.0, 175.9; LD-MS obsd
612.8; FAB-MS obsd 613.1958, calcd 613.1961 [(M + H)+, M )
C37H33N4Br]; λabs 411, 640 nm.
17,18-Dihydro-18,18-dimethyl-15-phenyl-10-p-tolylporphy-
rin (FbC-T10P15). Following a reported procedure,11 samples of
FbC-T10Br15 (32 mg, 0.063 mmol), 4,4,5,5-tetramethyl-2-phenyl-
1,3,2-dioxaborolane (130 mg, 0.637 mmol), Pd(PPh3)4 (22.2 mg,
0.0192 mmol), and K2CO3 (70 mg, 0.51 mmol) were placed in a
Schlenk flask. The flask was pumped-purged with argon three times.
A degassed mixture of toluene/DMF (3:1, 6.3 mL) was added. The
resulting mixture was stirred at 90-95 °C for 19 h. The reaction
mixture was diluted with CH2Cl2 and filtered. The filtrate was
concentrated. The crude product was chromatographed [silica, CH2-
Cl2/hexanes (1:1)]. The first fraction (blue, trace) was discarded,
and the second (green-brown) was concentrated and rechromato-
graphed [silica, hexanes/CH2Cl2 (3:2)] to afford a green-purple solid
(25 mg, 79%): 1H NMR (300 MHz) δ -2.14 (br s, 1H), -1.96
(br s, 1H), 1.96 (s, 6H), 2.66 (s, 3H), 4.17 (s, 2H), 7.50 (d, J ) 7.8
Hz, 2H), 7.67-7.72 (m, 3H), 7.86-7.88 (m, 2H), 7.99 (d, J ) 7.8
Hz, 2H), 8.24 (d, J ) 4.6 Hz, 1H), 8.63 (d, J ) 4.6 Hz, 1H), 8.67
(d, J ) 4.4 Hz, 1H), 8.89 (s, 1H), 8.91-8.92 (m, 2H), 9.17 (d, J
) 4.2 Hz, 1H), 9.77 (s, 1H); 13C NMR δ 21.8, 31.5, 46.3, 52.4,
95.1, 104.2, 112.9, 122.7, 123.8, 124.5, 127.8, 128.3, 128.6, 129.1,
132.6, 132.9, 134.1, 135.1, 135.3, 137.7, 138.8, 140.9, 141.4, 143.3,
7-Bromo-17,18-dihydro-18,18-dimethyl-15-phenyl-10-p-tolylpor-
phyrin (FbC-Br7T10P15). A solution of FbC-T10P15 (19 mg, 0.038
mmol) in THF (19 mL) was treated with NBS (0.375 mL, 0.100
M in THF). The resulting mixture was stirred at room temperature
for 1 h. The reaction mixture was diluted with CH2Cl2 (∼30 mL)
and quenched by the addition of saturated aqueous NaHCO3. The
organic phase was separated, washed with water and brine, dried
(Na2SO4), and concentrated. The resulting brown solid was chro-
matographed [silica, hexanes/CH2Cl2 (1:1)]. The first fraction
(purple-brown) was collected and rechromatographed [silica, hex-
anes/CH2Cl2 (3:2)]. The first fraction (pink-brown) was discarded,
and the second (pink-purple-brown) was concentrated to provide a
purple-brown solid (14 mg, 63%): 1H NMR δ -2.12 (br s, 1H),
-1.96 (br s, 1H), 1.96 (s, 6H), 2.66 (s, 3H), 4.17 (s, 2H), 7.49 (d,
J ) 7.8 Hz, 2H), 7.68-7.70 (m, 3H), 7.86-7.92 (m, 2H), 7.96 (d,
J ) 7.8 Hz, 2H), 8.22 (d, J ) 4.4 Hz, 1H), 8.61 (s, 1H), 8.64 (d,
J ) 4.4 Hz, 1H), 8.89 (s, 1H), 8.93 (d, J ) 4.4 Hz, 1H), 9.24 (d,
J ) 4.4 Hz, 1H), 9.96 (s, 1H); 13C NMR δ 21.7, 31.4, 46.3, 52.4,
95.0, 104.2, 112.8, 120.4, 122.7, 123.7, 124.4, 127.7, 128.2, 128.6,
129.0, 132.6, 132.8, 134.1, 135.0, 135.3, 137.7, 138.8, 140.9, 141.4,
7748 J. Org. Chem., Vol. 72, No. 20, 2007

Two Complementary Routes to 7-Substituted Chlorins
143.2, 147.7, 150.3, 163.1, 176.1 (the resonance of one carbon is
apparently overlapped with another); LD-MS obsd 584.2; FAB-
MS obsd 585.1648, calcd 585.1648 [(M + H)+, M ) C35H29N4-
Br]; λabs 412, 639 nm.
Cl2 (3:2)] provided a trace amount of an unidentified dibromochlorin
(first fraction, purple), a mixture of two products (second fraction,
brown), and unreacted starting material (third fraction, violet). The
second fraction was concentrated and rechromatographed [silica,
4.5 diameter × 40 cm, hexanes/CH2Cl2 (2:1)] to afford a trace of
discarded material (first fraction, pink), the title compound (second
fraction, pink-brown), and a second product tentatively assigned
as FbC-T5P15Br20 (third fraction, pink, ∼2 mg). Data for the title
compound: violet crystals, 21.6 mg (65%); 1H NMR δ -2.02 (br
s, 1H), -1.64 (br s, 1H), 1.97 (s, 6H), 2.68 (s, 3H), 4.22 (s, 2H),
7.54 (d, J ) 7.8 Hz, 2H), 7.69-7.75 (m, 3H), 7.91-7.93 (m, 2H),
8.02 (d, J ) 7.8 Hz, 2H), 8.40-8.41 (m, 1H), 8.66 (s, 1H), 8.82-
15-Bromo-17,18-dihydro-18,18-dimethyl-5-p-tolylporphyrin
(FbC-T5Br15). A solution of FbC-T5 (72.0 mg, 0.167 mmol) in
THF (67 mL) was treated with NBS (1.67 mL, 0.100 M in THF).
The resulting mixture was stirred at room temperature for 1 h. The
reaction mixture was diluted with CH2Cl2 (∼50 mL) and quenched
by the addition of aqueous NaHCO3. The organic layer was
separated, and the aqueous phase was extracted with CH2Cl2. The
organic extract was washed with water and brine, dried (Na2SO4),
and concentrated. Column chromatography [silica, hexanes/CH2-
Cl2 (1:1)] afforded a trace amount of an unidentified dibromochlorin
(first fraction, pink-brown) and the title compound (second fraction,
brown). Data for the title compound: purple-violet crystals (52.8
mg, 62%); 1H NMR δ -2.23 (br s, 1H), -1.68 (br s, 1H), 2.02 (s,
6H), 2.66 (s, 3H), 4.63 (s, 2H), 7.51 (d, J ) 7.8 Hz, 2H), 8.00 (d,
J ) 7.8 Hz, 2H), 8.62 (d, J ) 4.2 Hz, 1H), 8.82 -8.83 (m, 3H),
8.91 (d, J ) 4.2 Hz, 1H), 9.11-9.12 (m, 1H), 9.17-9.18 (m, 1H),
9.77 (s, 1H); 13C NMR δ 21.8, 31.8, 46.6, 54.7, 95.4, 95.7, 109.2,
121.9, 123.9, 125.1, 128.0, 128.6, 129.0, 132.4, 133.4, 134.2, 134.3,
136.8, 137.6, 138.5, 139.1, 140.7, 150.8, 154.4, 163.0, 175.7; LD-
MS obsd 508.5; FAB-MS obsd 509.1336, calcd 509.1335 [(M +
H)+, M ) C29H25N4Br]; λabs 403, 642 nm.
17,18-Dihydro-18,18-dimethyl-15-phenyl-5-p-tolylporphy-
rin (FbC-T5P15). Samples of FbC-T5Br15 (48.6 mg, 0.095 mmol),
4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (198 mg, 0.971
mmol), Pd(PPh3)4 (30.6 mg, 0.0264 mmol), and K2CO3 (106 mg,
0.769 mmol) were placed in a Schlenk flask. The flask was pump-
purged with argon three times. A degassed mixture of toluene/DMF
(3:1, 9.6 mL) was added. The resulting mixture was stirred at 90-
95 °C for 19 h. The reaction mixture was diluted with CH2Cl2 and
filtered. The filtrate was concentrated. The crude product was
chromatographed [silica, CH2Cl2/hexanes (2:3)], which afforded
three fractions. The first fraction (blue, trace) was discarded, the
second contained the title compound (violet), and third contained
debrominated byproduct (green, ∼4 mg, FbC-T5). Data for the title
compound: violet-purple crystals (30.8 mg, 64%); 1H NMR δ
-2.12 (s, 1H), -1.62 (s, 1H), 1.97 (s, 6H), 2.67 (s, 3H), 4.23 (s,
2H), 7.53 (d, J ) 7.6 Hz, 2H), 7.68-7.73 (m, 3H), 7.91-7.94 (m,
2H), 8.05 (d, J ) 7.6 Hz, 2H), 8.38-8.40 (m, 1H), 8.68 (d, J )
4.2 Hz, 1H), 8.85-8.89 (m, 2H), 8.92 (s, 1H), 8.95 (d, J ) 4.2 Hz,
1H), 9.07-9.09 (m, 1H), 9.83 (s, 1H); 13C NMR δ 21.7, 31.6, 46.4,
52.1, 95.3, 107.9, 111.9, 121.7, 123.3, 124.1, 127.7, 127.9, 128.1,
128.21, 128.25, 132.2, 132.6, 132.8, 134.2, 134.4, 136.0, 137.4,
138.7, 140.2, 141.0, 142.6, 150.9, 153.3, 163.1, 174.2; LD-MS
506.5, FAB-MS obsd 507.2543, calcd 507.2543 [(M + H)+, M )
C35H30N4]; λabs 411, 641 nm.
8.87 (m, 2H), 8.91 (s, 1H), 9.14-9.16 (m, 1H), 10.01 (s, 1H); 13
C
NMR δ 21.7, 31.5, 46.4, 52.1, 95.6, 105.3, 112.3, 120.9, 121.6,
123.9, 124.4, 127.8, 128.0, 128.3, 128.8, 129.0, 132.3, 132.7, 134.3,
134.5, 135.8, 137.7, 138.2, 140.6, 141.6, 142.3, 146.7, 150.9, 164.0,
174.9; LD-MS obsd 585.0, FAB-MS obsd 585.1651, calcd 585.1648
[(M + H)+, M ) C35H29N4Br]; λabs 414, 639 nm.
7,8-Dibromo-17,18-dihydro-18,18-dimethyl-15-phenylporphy-
rin (FbC-Br7,8P15). A solution of FbC-P15 (9.1 mg, 0.022 mmol)
in THF (11 mL) was treated with NBS (0.440 mL, 0.100 M in
THF). The resulting mixture was stirred for 30 min at room
temperature. The reaction mixture was diluted with CH2Cl2 (∼20
mL) and quenched by the addition of saturated aqueous NaHCO3.
The organic layer was separated, and the aqueous phase was
extracted with CH2Cl2. The organic extract was washed with water
and brine, dried (Na2SO4), and concentrated. The resulting solid
was dissolved in a minimal amount of CH2Cl2 and chromatographed
[silica, hexanes/CH2Cl2 (1:1)]. The first fraction (brown) was
collected and rechromatographed [silica, hexanes/CH2Cl2 (3:1)] to
afford a brown solid (3.9 mg, 31%): 1H NMR -2.41 (br s, 1H),
-2.33 (br s, 1H), 1.99 (s, 6H), 4.22 (s, 2H), 7.72-7.78 (m, 3H),
7.90-7.92 (m, 2H), 8.41-8.42 (m, 1H), 8.97 (s, 1H), 8.98-9.01
(m, 1H), 9.17-9.18 (m, 1H), 9.27-9.28 (m, 1H), 9.95 (s, 1H),
10.01 (s, 1H); LD-MS obsd 572.2, FAB-MS obsd 573.0277, calcd
573.0284 [(M + H)+, M ) C28H22N4Br2]; λabs 406, 635 nm. Note
that the small amount and low solubility of FbC-Br7,8P15 prevented
the recording of a 13C NMR spectrum.
Acknowledgment. This work was supported by a grant from
the Division of Chemical Sciences, Office of Basic Energy
Sciences, Office of Energy Research, U.S. Department of Energy
(DE-FG02-96ER14632). Mass spectra were obtained at the Mass
Spectrometry Laboratory for Biotechnology at North Carolina
State University. Partial funding for the Facility was obtained
from the North Carolina Biotechnology Center and the National
Science Foundation. The Department of Chemistry of North
Carolina State University and the State of North Carolina
provided funds to purchase the Apex2 diffractometer.
8-Bromo-17,18-dihydro-18,18-dimethyl-15-phenyl-5-p-tolylpor-
phyrin (FbC-T5Br8P15). A solution of FbC-T5P15 (28.7 mg, 0.0566
mmol) in THF (23 mL) was treated with NBS (0.566 mL, 0.100
M in THF). The resulting mixture was stirred for 1 h. The reaction
mixture was diluted with CH2Cl2 (∼50 mL) and quenched by the
addition of saturated aqueous NaHCO3. The organic layer was
separated, and the aqueous phase was extracted with CH2Cl2. The
organic extract was washed with water and brine, dried (Na2SO4),
and concentrated. Column chromatography [silica, hexanes/CH2-
Supporting Information Available: Synthesis of three dipyr-
romethanes as part of exploratory studies; streamlined synthesis of
ZnC-T5; crystallographic data for ZnC-Br7T10; complete 1H NMR
assignments for selected 7-substituted chlorins; and spectral data
for all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO701500D
J. Org. Chem, Vol. 72, No. 20, 2007 7749