A new route for installing the isocyclic ring on chlorins yielding 13 1-oxophorbines

Article abstract of DOI:10.1021/jo0608265

A new route to 13¹-oxophorbines, the parent macrocycle of chlorophylls, begins with the synthesis of a 13-bromochlorin. Pd-mediated coupling of the latter with tributyl(1-ethoxyvinyl)tin and subsequent acidic hydrolysis afforded the 13-acetylch

Full text of DOI:10.1021/jo0608265

SCHEME 1
A New Route for Installing the Isocyclic Ring on
Chlorins Yielding 131-Oxophorbines
Joydev K. Laha,† Chinnasamy Muthiah,†
Masahiko Taniguchi, and Jonathan S. Lindsey*
Department of Chemistry, North Carolina State UniVersity,
Raleigh, North Carolina 27695-8204
jlindsey@ncsu.edu
ReceiVed April 19, 2006
A new route to 131-oxophorbines, the parent macrocycle of
chlorophylls, begins with the synthesis of a 13-bromochlorin.
Pd-mediated coupling of the latter with tributyl(1-ethoxyvi-
nyl)tin and subsequent acidic hydrolysis afforded the 13-
acetylchlorin (1). Treatment of 1 with NBS afforded the 15-
bromo analogue in 70% yield. Pd-mediated R-arylation
closed the isocyclic ring to give the 131-oxophorbine (2) in
85% yield. Facile access to 131-oxophorbines should enable
a variety of spectroscopic studies and diverse applications.
Introduction
The fundamental skeleton of chlorophylls is a phorbine, which
differs from porphyrins in containing one reduced pyrrole ring
and a five-membered exocyclic ring. The exocyclic ring (known
as the isocyclic ring) is ortho-perifused across the 13- and 15-
positions and contains a 131-oxo group.1 Chlorophyll a absorbs
strongly in the blue (B band, ∼430 nm) and the red (Qy band,
∼660 nm) regions of the visible spectrum. The 13-keto group,
which is conjugated with the π-electrons of the macrocycle,
causes a significant red-shift and intensification of the Qy band
compared to synthetic chlorins lacking a 13-keto substituent.2
Intense absorption in the red region is attractive for applications
encompassing solar cells,3 medical imaging,4 and photodynamic
therapy.5 Moreover, the 13-keto substituent is an essential motif
for self-assembly of certain chlorophyll species.6
SO4 to give the “pheoporphyrin” bearing the isocyclic ring (A
f B),8 and Dieckmann cyclization to convert chlorin e6
trimethyl ester to methyl pheophorbide a (C f D).9,10 The
Dieckmann cyclization has been carried out using KOH/
pyridine,9 sodium methoxide in methanol/acetone,10 potassium
tert-butoxide/pyridine,11 sodium bis(trimethylsilylamide),12 or
potassium tert-butoxide/collidine.13 Kenner employed oxidative
cyclization with a porphyrin bearing a â-ketoester to give the
pheoporphyrin,14 a route extended by Smith for conversion of
a chlorin to the methyl pheophorbide a (E f D).15 Finally, a
(6) Balaban, T. S.; Tamiaki, H.; Holzwarth, A. R. Top. Curr. Chem.
2005, 258, 1-38.
(7) Pavlov, V. Y.; Ponomarev, G. V. Chem. Heterocycl. Compd. 2004,
40, 393-425.
Surprisingly few routes are known for the construction of
the isocyclic ring (Scheme 1).7 Fischer reported the dehydration
of a (hydroxymethylcarbonyl)porphyrin using concentrated H2-
(8) Fischer, H.; Laubereau, O. Justus Liebigs Ann. Chem. 1938, 535,
17-37.
(9) Fischer, H.; Lautsch, W. Justus Liebigs Ann. Chem. 1937, 528, 265-
275.
† Equal contributions by both authors.
(1) Scheer, H. In Chlorophylls; Scheer, H., Ed.; CRC Press: Boca Raton,
FL, 1991; pp 3-30.
(2) Boldt, N. J.; Donohoe, R. J.; Birge, R. R.; Bocian, D. F. J. Am. Chem.
Soc. 1987, 109, 2284-2298.
(3) Linke-Schaetzel, M.; Bhise, A. D.; Gliemann, H.; Koch, T.; Schim-
mel, T.; Balaban, T. S. Thin Solid Films 2004, 451, 16-21.
(4) Licha, K. Top. Curr. Chem. 2002, 222, 1-29.
(5) Nyman, E. S.; Hynninen, P. H. J. Photochem. Photobiol. B: Biol.
2004, 73, 1-28.
(10) Fischer, H.; Oestreicher, A. Justus Liebigs Ann. Chem. 1940, 546,
49-57.
(11) (a) Smith, K. M.; Bisset, G. M. F.; Bushell, M. J. Bioorg. Chem.
1980, 9, 1-26. (b) Smith, K. M.; Bushell, M. J.; Rimmer, J.; Unsworth, J.
F. J. Am. Chem. Soc. 1980, 102, 2437-2448. (c) Smith, K. M.; Bisset, G.
M. F.; Bushell, M. J. J. Org. Chem. 1980, 45, 2218-2224.
(12) Gerlach, B.; Brantley, S. E.; Smith, K. M. J. Org. Chem. 1998, 63,
2314-2320.
(13) Pallenberg, A. J.; Dobhal, M. P.; Pandey, R. K. Org. Process Res.
DeV. 2004, 8, 287-290.
10.1021/jo0608265 CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/02/2006
J. Org. Chem. 2006, 71, 7049-7052
7049

SCHEME 2
dipyrromethane bearing an annulated oxocyclopentanyl ring (F)
provided an intriguing route to deoxophylloerythroetioporphyrin
(G), although this macrocycle is a porphyrin and lacks the
desired 13-keto functionality.16 Lash has employed annulated
dipyrromethanes in the synthesis of G and related porphyrin
analogues.17 Each of these routes has certain attractions;
however, none appeared compatible with our existing synthetic
route to chlorins.
We have developed synthetic methods for preparing chlorins
wherein each chlorin incorporates a geminal dimethyl moiety
in the reduced, pyrroline ring to block adventitious dehydro-
genation.18,19 We recently exploited this route to gain access to
chlorins bearing substituents that afford enhanced red absorption
spectral features, including 3-acetyl, 3-ethynyl, 3-vinyl, 13-
acetyl, and 13-ethynyl groups.20 Here, we describe extension
of the route for preparing 13-acetylchlorins to install the
isocyclic ring under mild reaction conditions.
ature followed by S-2-pyridyl 4-methylbenzothioate22 at -78
°C gave 1-acyldipyrromethane 3 in 73% yield, to be compared
with 37% achieved previously upon acylation with p-toluoyl
chloride.18 Treatment of 3 with 2.2 molar equiv of NBS at -78
°C gave the 8,9-dibromo-product 4 along with several side
products (Scheme 2). Although somewhat labile, compound 4
could be handled effectively by workup without heating and
by avoiding adverse solvents (ethyl acetate, chlorinated hydro-
carbons; see Supporting Information) and was obtained follow-
ing column chromatography in 57% yield. The 8,9-dibromo-
substitution pattern in 4 was established by NMR spectroscopy
(1H-1H 2D-COSY and NOESY experiments).
B. Chlorin Formation. Reduction of 4 with NaBH4 at room
temperature for 3 h gave the corresponding dipyrromethane-1-
carbinol (Eastern half), which was condensed with Western half
523 under the standard conditions19 of TFA catalysis. The
putative tetrahydrobilene-a formed in situ was subjected to
metal-catalyzed oxidative cyclization (2,2,6,6-tetramethylpip-
eridine, Zn(OAc)2, and AgOTf) in refluxing acetonitrile in the
presence of air for 18 h, affording the zinc chelate of the 13-
bromochlorin (Zn-6) in 20% yield (from 4).
The conversion of the 13-bromochlorin to the 13-acetylchlorin
was carried out by Pd-mediated coupling using tributyl(1-
ethoxyvinyl)tin24 followed by acidic hydrolysis of the resulting
enol ether. Use of the zinc chlorin Zn-6 gave limited
conversion upon reaction in refluxing toluene (7% yield) or THF
(∼29% yield). The synthesis of 1 was improved by carrying
out the palladium coupling using free base chlorin 6, which
was obtained in 88% yield by demetalation of Zn-6 with TFA
in CH2Cl2 at room temperature. The coupling of 6 (20 mM)
Results and Discussion
A. Chlorin Precursors. Treatment of 5-mesityldipyr-
romethane21 with 3.0 molar equiv of EtMgBr at room temper-
(14) (a) Cox, M. T.; Howarth, T. T.; Jackson, A. H.; Kenner, G. W. J.
Am. Chem. Soc. 1969, 91, 1232-1233. (b) Kenner, G. W.; McCombie, S.
W.; Smith, K. M. J. Chem. Soc. Chem. Comm. 1972, 844-845. (c) Cox,
M. T.; Howarth, T. T.; Jackson, A. H.; Kenner, G. W. J. Chem. Soc., Perkin
Trans. 1 1974, 512-516. (d) Kenner, G. W.; McCombie, S. W.; Smith, K.
M. J. Chem. Soc., Perkin Trans. 1 1974, 527-530.
(15) Smith, K. M.; Lewis, W. M. Tetrahedron 1981, 37 Supp. 1, 399-
403.
(16) Flaugh, M. E.; Rapoport, H. J. Am. Chem. Soc. 1968, 90, 6877-
6879.
(17) (a) Zhang, B.; Lash, T. D. Tetrahedron Lett. 2003, 44, 7253-7256.
(b) Lash, T. D.; Quizon-Colquitt, D. M.; Shiner, C. M.; Nguyen, T. H.;
Hu, Z. Energy Fuels 1993, 7, 172-178.
(21) Laha, J. K.; Dhanalekshmi, S.; Taniguchi, M.; Ambroise, A.;
Lindsey, J. S. Org. Process Res. DeV. 2003, 7, 799-812.
(22) Rao, P. D.; Littler, B. J.; Geier, G. R., III; Lindsey, J. S. J. Org.
Chem. 2000, 65, 1084-1092.
(18) Strachan, J.-P.; O’Shea, D. F.; Balasubramanian, T.; Lindsey, J. S.
J. Org. Chem. 2000, 65, 3160-3172.
(19) Taniguchi, M.; Ra, D.; Mo, G.; Balasubramanian, T.; Lindsey, J.
S. J. Org. Chem. 2001, 66, 7342-7354.
(20) Laha, J. K.; Muthiah, C.; Taniguchi, M.; McDowell, B. E.; Ptaszek,
M.; Lindsey, J. S. J. Org. Chem. 2006, 71, 4092-4102.
(23) Ptaszek, M.; Bhaumik, J.; Kim, H.-J.; Taniguchi, M.; Lindsey, J.
S. Org. Process Res. DeV. 2005, 9, 651-659.
(24) Kosugi, M.; Sumiya, T.; Obara, Y.; Suzuki, M.; Sano, H.; Migita,
T. Bull. Chem. Soc. Jpn. 1987, 60, 767-768.
7050 J. Org. Chem., Vol. 71, No. 18, 2006

TABLE 1. Spectral Properties of Chlorins and 131-Oxophorbinesa
b
c
e
f
compound
λ
B (fwhm) in nm
logꢀB
λ
Qy (fwhm) in nm
logꢀQy
∆νQy (cm-1
)
IB/IQ
λ
em (nm)d
∆ν(cm-1
)
Φf
Zn-8
Zn-1
Zn-2
412 (13)g
424 (17)h
431 (16)i
5.27
5.30
5.15
608 (11)
635 (14)
643 (11)
4.64
4.85
4.84
0
700
900
4.9
2.8
2.1
611
639
646
80
100
70
0.062
0.25
0.28
8
1
2
414 (34)j
423 (36)
417 (49)k
4.95
5.14
5.00
641 (9)
661 (13)
660 (11)
4.45
4.72
4.71
0
470
450
3.3
2.6
2.0
643
665
663
50
90
70
0.23
0.25
0.37
Zn-Pheo al,m
423 (38)
410 (63q)
433 (39q)
5.09
4.97
5.01
653 (18)
667 (21q)
666 (19q)
4.96
4.65
4.89
-
-
-
1.4
2.1
1.3
657
90n
180q
110q
0.23n
0.28r
Pheo ao,p
675q
Chl as,t
671q
0.325u
a In toluene at room temperature unless noted otherwise. b The redshift of the Qy band relative to that of the parent chlorin (8 or Zn-8). c Ratio of the
intensities of the B and Qy bands. d Excitation was performed at the λmax of the B band. e Stokes shift. f Determined with λexc at the B band maximum using
chlorophyll a as a standard (Φf ) 0.322) unless noted otherwise (see Supporting Information). g Shoulder at 391 nm. h Shoulder at 402 nm. i Shoulder at 409
nm (log ꢀ ) 4.73). j Shoulder at 398 nm. k Shoulder at 431 nm (log ꢀ ) 4.97). l In diethyl ether. m Absorption data from ref 30. The absorption spectrum
is essentially identical in CHCl3.29 n Reference 32. The Φf value was calculated using data from ref 32 with chlorophyll a as standard. A value of Φf ) 0.17
in diethyl ether/petroleum ether has been reported.31 o In ethanol. p Absorption and emission data from ref 33. q This work. r In ethanol. The Φf in toluene
was found to be as follows: Pheophorbide a (0.26), pyropheophorbide a (0.29), pyropheophorbide a methyl ester (0.30). s In benzene. t Absorption data
from ref 28. u Reference 27.
CHART 1
and tributyl(1-ethoxyvinyl)tin (40 mM) in the presence of 15
mol % of (PPh3)2PdCl2 in THF for 20 h followed by hydrolysis
with 10% aqueous HCl gave 13-acetylchlorin 1 in 74% yield.
A streamlined procedure including demetalation, Pd-coupling,
and acidic workup gave 1 in 68% yield starting from Zn-6.
The free-base 13-acetylchlorin 1 was metalated with Zn(OAc)2‚
2H2O or Cu(OAc)2‚H2O to obtain Zn-1 or Cu-1, respectively.
The chlorins were characterized by mass spectrometry (LD-
MS, FAB-MS) and absorption, fluorescence, and 1H NMR
spectroscopy. The X-ray structure of Cu-1 confirmed the
presence of the acetyl group at the 13-position of the chlorin
Qy band (27 nm), increases the intensity of the Qy band (1.6-
macrocycle (Supporting Information).
fold), and alters the IB/IQ ratio from 4.9 to 2.8. Similar trends
C. Isocyclic Ring Installation. The R-arylation of aliphatic
ketones has been carried out on a wide variety of aryl substrates,
including aryl bromides under Pd-mediated coupling condi-
tions.25 Treatment of 1 to conditions for 15-bromination (1 equiv
of NBS at room temperature for 1 h)26 gave the 15-bromochlorin
7 in 70% yield. The reaction of 7 under conditions for
R-arylation [(PPh3)2PdCl2 in the presence of Cs2CO3 in toluene
at reflux]25 for 24 h gave oxophorbine 2 in 85% yield. A
combined procedure of bromination and Pd-mediated ring
closure gave oxophorbine 2 in 44% yield from 1. Treatment of
2 with Zn(OAc)2‚2H2O at room temperature gave Zn-2 in 85%
yield. Oxophorbines 2 and Zn-2 were characterized by mass
spectrometry (LD-MS, FAB-MS) and absorption, fluorescence,
y
are observed in the free base chlorins.
(2) Absorption spectral effects of the isocyclic ring: The
presence of the isocyclic ring in the zinc complex (Zn-2 vs
Zn-8) red-shifts the Qy band by 35 nm and increases the
intensity of the Qy band (1.5-fold). A similar trend was observed
for the free base oxophorbine 2, although the magnitude was
less pronounced than for the zinc complexes given that the Qy
band of free base chlorin 8 appears at 641 nm. The absorption
spectrum of the free base oxophorbine 2 closely resembles that
of pheophorbide a (667 nm),33,34 a free base analogue of
chlorophyll a (see Supporting Information for overlaid spectra).
(3) Fluorescence yields: The fluorescence quantum yield (Φf)
increases by >4-fold in going from the benchmark zinc chlorin
(Zn-8, Φf ) 0.062) to the zinc 13-acetylchlorin Zn-1 or zinc
oxophorbine Zn-2. The yields are comparable to that of the
chlorophyll derivative Zn-Pheo a (0.23). The effect of
introducing a keto substituent in the free base compounds is
less pronounced, where the parent chlorin 8 is already rather
emissive (Φf ) 0.23).
1
IR and H NMR spectroscopy.
D. Spectral Properties. The spectral properties of the 13-
acetylchlorins and 131-oxophorbines are listed in Table 1,
accompanied by those of chlorophyll a (Chl a),27,28 the zinc
(Zn-Pheo a)29-32 and free base (Pheo a)33,34 analogues of
chlorophyll a, as well as benchmark zinc or free base chlorins
(Zn-8, 8)18 lacking a 13-substituent (Chart 1). The absorption
spectra of the synthetic oxophorbines and chlorins are shown
in Figure 1. The major observations are as follows:
(4) IR properties: 13-Acetylchlorin 1 exhibits a carbonyl
stretch (νmax) at 1728 cm-1, whereas that of oxophorbine 2
appears at 1701 cm-1. The latter matches well with that of
(1) Absorption spectral effects of the 13-acetyl substituent:
The presence of the 13-acetyl substituent in the zinc complex
(Zn-1 vs. Zn-8) red-shifts both the B band (12 nm) and the
(29) Boucher, L. J.; Katz, J. J. J. Am. Chem. Soc. 1967, 89, 4703-4708.
(30) Jones, I. D.; White, R. C.; Gibbs, E.; Denard, C. D. J. Agric. Food
Chem. 1968, 16, 80-83.
(25) (a) Muratake, H.; Natsume, M. Tetrahedron Lett. 1997, 38, 7581-
7582. (b) Muratake, H.; Natsume, M.; Nakai, H. Tetrahedron 2004, 60,
(31) Dvornikov, S. S.; Knyukshto, V. N.; Solovev, K. N.; Tsvirko, M.
P. Opt. Spectrosc. USSR 1979, 46, 385-388.
11783-11803.
(32) Agostiano, A.; Catucci, L.; Colafemmina, G.; Scheer, H. J. Phys.
Chem. B 2002, 106, 1446-1454.
(26) Taniguchi, M.; Kim, M. N.; Ra, D.; Lindsey, J. S. J. Org. Chem.
2005, 70, 275-285.
(33) Eichwurzel, I.; Stiel, H.; Ro¨der, B. J. Photochem. Photobiol. B:
Biol. 2000, 54, 194-200.
(27) Weber, G.; Teale, F. W. J. Trans. Faraday Soc. 1957, 53, 646-
655.
(34) Smith, J. H. C.; Benitez, A. In Modern Methods of Plant Analysis;
Paech, K., Tracey, M. V., Eds.; Springer-Verlag: Berlin, 1955; Vol. IV,
pp 142-196.
(28) Seely, G. R.; Jensen, R. G. Spectrochim. Acta 1965, 21, 1835-
1845.
J. Org. Chem, Vol. 71, No. 18, 2006 7051

(br, 2H), 1.86 (s, 6H), 2.02 (s, 6H), 2.61 (s, 3H), 2.66 (s, 3H), 3.05
(s, 3H), 4.56 (s, 2H), 7.24 (s, 2H), 7.50 (d, J ) 7.8 Hz, 2H), 7.96
(d, J ) 7.8 Hz, 2H), 8.23 (d, J ) 4.4 Hz, 1H), 8.31 (d, J ) 4.4 Hz,
1H), 8.68 (d, J ) 4.4 Hz, 1H), 8.69 (s, 1H), 8.70 (d, J ) 4.4 Hz,
1H), 8.86 (s, 1H), 9.98 (s, 1H); LD-MS obsd 590.6; FAB-MS obsd
590.3052, calcd 590.3046 (C40H38N4O); λabs 423 (log ꢀ ) 5.14),
661 (4.72) nm; λem 665 (Φf ) 0.25).
15-Bromination: 13-Acetyl-15-bromo-17,18-dihydro-10-mesi-
tyl-18,18-dimethyl-5-p-tolylporphyrin (7). Following a reported
procedure,26 a solution of 1 (26.4 mg, 0.0447 mmol) in THF (22
mL) was treated with NBS (7.95 mg, 0.0447 mmol) at room
temperature for 1 h. CH2Cl2 was added. The mixture was washed
with aqueous NaHCO3. The organic layer was dried (Na2SO4),
concentrated, and chromatographed [silica, hexanes then CH2Cl2/
hexanes (3:1)], affording a purple solid (20.8 mg, 70.%): 1H NMR
δ -1.30 to -1.40 (br, 1H), -0.98 to -1.02 (br, 1H), 1.86 (s, 6H),
2.04 (s, 6H), 2.60 (s, 3H), 2.66 (s, 3H), 3.06 (s, 3H), 4.55 (s, 2H),
7.21 (s, 2H), 7.51 (d, J ) 7.8 Hz, 2H), 7.96 (d, J ) 7.8 Hz, 2H),
8.26 (d, J ) 4.4 Hz, 1H), 8.34 (d, J ) 4.4 Hz, 1H), 8.45 (s, 1H),
8.70-8.76 (m, 3H); LD-MS obsd 668.4; FAB-MS obsd 668.2145,
calcd 668.2150 (C40H37BrN4O); λabs 418, 652 nm.
Installation of the Isocyclic Ring: 18,18-Dimethyl-10-mesityl-
131-oxo-5-p-tolylphorbine (2). A mixture of 7 (20.2 mg, 0.0301
mmol), Cs2CO3 (49.0 mg, 0.150 mmol), and (PPh3)2PdCl2 (4.22
mg, 0.0125 mmol) was refluxed in toluene (3.0 mL) for 24 h in a
Schlenk line. CH2Cl2 was added. The reaction mixture was washed
with water and brine. The organic layer was dried (Na2SO4),
concentrated, and chromatographed [silica, hexanes then hexanes/
Et2O (1:1)], affording a purple solid (15.1 mg, 85%): IR 1701 cm-1
;
1H NMR δ -1.25 (br, 1H), 0.73 (br, 1H), 1.88 (s, 6H), 2.02 (s,
6H), 2.57 (s, 3H), 2.65 (s, 3H), 4.27 (s, 2H), 5.12 (s, 2H), 7.20 (s,
2H), 7.49 (d, J ) 7.8 Hz, 2H), 7.93 (d, J ) 7.8 Hz, 2H), 8.22 (d,
J ) 4.4 Hz, 1H), 8.28 (d, J ) 4.4 Hz, 1H), 8.53 (s, 1H), 8.58 (s,
1H), 8.62 (d, J ) 4.4 Hz, 1H), 8.70 (d, J ) 4.4 Hz, 1H); LD-MS
obsd 589.2; FAB-MS obsd 589.2971, calcd 589.2967 [(M+H)+,
M ) C40H36N4O]; λabs 417 (log ꢀ ) 5.00), 431 (sh, 4.97), 660 (4.71)
nm; λem 663 (Φf ) 0.37).
FIGURE 1. Absorption spectra in toluene at room temperature. Upper
panel: free base compounds (color in graph; Qy band position) include
8 (black, 641 nm); 1 (blue, 661 nm); 2 (red, 660 nm). Lower panel:
zinc chelates include Zn-8 (black, 608 nm); Zn-1 (blue, 635 nm);
Zn-2 (red, 643 nm).
Zinc Insertion: Zn(II)-10-Mesityl-18,18-dimethyl-131-oxo-5-
p-tolylphorbine (Zn-2). A solution of Zn(OAc)2‚2H2O (106 mg,
0.484 mmol) in methanol (1.4 mL) was added to a solution of 2
(19.0 mg, 0.0323 mmol) in CHCl3 (5.6 mL) with stirring at room
temperature. After 16 h, the reaction mixture was concentrated,
and CH2Cl2 was added. The organic layer was washed (saturated
aqueous NaHCO3, H2O), dried (Na2SO4), and filtered. The filtrate
was concentrated to dryness. The resulting solid was washed with
hexanes several times. The solid was dissolved in a minimum
amount of methanol, and then hexanes was added (∼2:1 ratio of
hexanes/methanol), affording a green solid (18.0 mg, 85%): 1H
NMR (THF-d8) δ 1.88 (s, 6H), 2.03 (s, 6H), 2.56 (s, 3H), 2.63 (s,
3H), 4.30 (s, 2H), 5.00 (s, 2H), 7.22 (s, 2H), 7.47 (d, J ) 7.6 Hz,
2H), 7.88 (d, J ) 7.6 Hz, 2H), 8.15 (d, J ) 4.4 Hz, 1H), 8.18 (d,
J ) 4.4 Hz, 1H), 8.33 (s, 1H), 8.48 (s, 1H), 8.50 (d, J ) 4.4 Hz,
1H), 8.62 (d, J ) 4.4 Hz, 1H); LD-MS obsd 650.2; FAB-MS obsd
650.2031, calcd 650.2024 (C40H34N4OZn); λabs 409 (sh, log ꢀ )
4.73), 431 (5.15), 643 (4.84) nm; λem 646 (Φf ) 0.28).
pheophytin a (1705 cm-1),35 methyl pheophorbide a (1703
cm-1),35 and methyl pyropheophorbide a (1695 cm-1).35
In summary, a new route has been developed for installing
the isocyclic ring on tetrapyrrole macrocycles. The route entails
preparation of a 13-acetylchlorin, which undergoes bromination
at the 15-position followed by a Pd-mediated R-arylation
procedure to close the ortho-perifused ring. The presence of a
keto group at the 13-position significantly red-shifts the absorp-
tion maximum and increases the intensity of the Qy band. The
ability to install the isocyclic ring opens a number of possible
applications ranging from artificial photosynthesis to pho-
tomedicine.
Experimental Section
13-Acetylation: 13-Acetyl-17,18-dihydro-10-mesityl-18,18-
dimethyl-5-p-tolylporphyrin (1). Following a procedure for Stille
coupling on aromatic compounds,24 a mixture of 6 (19.8 mg, 0.0315
mmol), tributyl(1-ethoxyvinyl)tin (21.3 µL, 0.0630 mmol), and
(PPh3)2PdCl2 (3.40 mg, 0.00472 mmol) was refluxed in THF (1.5
mL) for 20 h in a Schlenk line. The reaction mixture was treated
with 10% aqueous HCl (1 mL) at room temperature for 2 h. CH2-
Cl2 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 chro-
matographed [silica, hexanes then CH2Cl2/hexanes (1:1)], affording
Acknowledgment. This research work was supported by the
NIH (GM36238). Mass spectra were obtained at the Mass
Spectrometry Laboratory for Biotechnology at North Carolina
State University. Partial funding for the Facility was obtained
from the North Carolina Biotechnology Center and the National
Science Foundation.
Supporting Information Available: Complete experimental
procedures; description of phorbine nomenclature; crystallographic
data for Cu-1. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
a purple solid (13.7 mg, 74%): IR 1728 cm-1; H NMR δ -0.98
(35) Katz, J. J.; Dougherty, R. C.; Boucher, L. J. In The Chlorophylls;
Vernon, L. P., Seely, G. R., Eds.; Academic Press: New York, 1966; pp
185-251.
JO0608265
7052 J. Org. Chem., Vol. 71, No. 18, 2006