3-Cyclobutenyl-1,2-dione-substituted porphyrins. A general and efficient entry to porphyrin-quinone and quinone-porphyrin-quinone architectures

Article abstract of DOI:10.1021/jo9912799

A new and efficient synthesis of meso-linked porphyrin-quinone dyads and quinone-porphyrin-quinone triads has been developed via the intermediacy of porphyrins bearing 3-cyclobutenyl-1,2-dione and 3-(1-ethenyl)cyclobutenyl- 1,2-dione substituents at one or two nonadjacent meso-positions. The free- base porphyrins 5-bromo-10,20-diphenylporphyrin and 5,15-dibromo-10,20- diphenylporphyrin undergo facile palladium-catalyzed Stille coupling with 3- isopropoxy-2-tri-n-butylstannylcyclobutene-1,2-dione to produce the corresponding mono- and bis(3-cyclobutenyl-1,2-dione)-substituted porphyrins in good yields. In contrast, the zinc bromoporphyrins reacted with the same tin reagent only slowly and with the formation of side products. The free- base bromoporphyrins also were coupled with tri-n-butylvinyltin to afford vinylporphyrins in very good yields. 5,15-Diphenyl-10-vinylporphyrin was converted into trans-bromovinylporphyrin, which underwent facile Stille coupling with 3-isopropoxy-2-tri-n-butylstannylcyclobutene-1,2-dione to afford the vinylogous 3-cyclobutenyl-1,2-dione-substituted porphyrin. The molecular structure of 5,15-bis(3-cyclobutenyl-1,2-dione)-10,20- diphenylporphyrin(Zn) was determined by X-ray crystallography. Although the data revealed a fairly large dihedral angle between the cyclobutenedione and the porphyrin rings (57°), the UV-vis spectra of both the mono- and bis(3- cyclobutenyl-1,2-dione)-substituted porphyrins showed B- and Q-band red shifts indicative of strong electronic coupling between the porphyrin and cyclobutenedione chromophores in solution. Introduction of a double bond between the cyclobutenedione and porphyrin rings resulted in a significant red shift of both the B- and Q-bands compared to those of the nonvinylogous system. All porphyrinic cyclobutenediones were metalated with zinc and then, using established cyclobutenedione chemistry, converted into a variety of porphyrin-quinones in excellent yields with aryllithium and vinylic Grignard reagents. From the mono(3-cyclobutenyl-1,2-dione)-substituted porphyrin, 7, a variety of directly linked monoquinone-porphyrin dyads were easily synthesized. Substituents could also be introduced at the free meso-position of 7 by bromination followed by palladium-catalyzed cross-coupling reactions, and additional porphyrinic monoquinones were then prepared from these starting materials. The vinylogous squarylporphyrin was converted into a double bond linked porphyrin-quinone via reaction with phenyllithium followed by thermal rearrangement and oxidation. As a result of the hindered rotation around the C-C bond between the porphyrin and the quinone, pairs of stable, separable, and thermally interconvertable atropisomers of porphyrin-quinones were obtained from 5,15-bis(3-cyclobutenyl-1,2-dione)-10,20- diphenylporphyrin(Zn). The structure of one of the atropisomers was determined by X-ray crystallography.

Full text of DOI:10.1021/jo9912799

1650
J . Org. Chem. 2000, 65, 1650-1664
3-Cyclobu ten yl-1,2-d ion e-Su bstitu ted P or p h yr in s. A Gen er a l a n d
Efficien t En tr y to P or p h yr in -Qu in on e a n d
Qu in on e-P or p h yr in -Qu in on e Ar ch itectu r es
Xianglin Shi, Sk. Rasidul Amin, and Lanny S. Liebeskind*
Sanford S. Atwood Chemistry Center, Emory University, 1515 Pierce Drive, Atlanta, Georgia 30322
Received August 11, 1999
A new and efficient synthesis of meso-linked porphyrin-quinone dyads and quinone-porphyrin-
quinone triads has been developed via the intermediacy of porphyrins bearing 3-cyclobutenyl-1,2-
dione and 3-(1-ethenyl)cyclobutenyl-1,2-dione substituents at one or two nonadjacent meso-positions.
The free-base porphyrins 5-bromo-10,20-diphenylporphyrin and 5,15-dibromo-10,20-diphenylpor-
phyrin undergo facile palladium-catalyzed Stille coupling with 3-isopropoxy-2-tri-n-butylstannyl-
cyclobutene-1,2-dione to produce the corresponding mono- and bis(3-cyclobutenyl-1,2-dione)-
substituted porphyrins in good yields. In contrast, the zinc bromoporphyrins reacted with the same
tin reagent only slowly and with the formation of side products. The free-base bromoporphyrins
also were coupled with tri-n-butylvinyltin to afford vinylporphyrins in very good yields. 5,15-
Diphenyl-10-vinylporphyrin was converted into trans-bromovinylporphyrin, which underwent facile
Stille coupling with 3-isopropoxy-2-tri-n-butylstannylcyclobutene-1,2-dione to afford the vinylogous
3-cyclobutenyl-1,2-dione-substituted porphyrin. The molecular structure of 5,15-bis(3-cyclobutenyl-
1,2-dione)-10,20-diphenylporphyrin(Zn) was determined by X-ray crystallography. Although the
data revealed a fairly large dihedral angle between the cyclobutenedione and the porphyrin rings
(57°), the UV-vis spectra of both the mono- and bis(3-cyclobutenyl-1,2-dione)-substituted porphyrins
showed B- and Q-band red shifts indicative of strong electronic coupling between the porphyrin
and cyclobutenedione chromophores in solution. Introduction of a double bond between the
cyclobutenedione and porphyrin rings resulted in a significant red shift of both the B- and Q-bands
compared to those of the nonvinylogous system. All porphyrinic cyclobutenediones were metalated
with zinc and then, using established cyclobutenedione chemistry, converted into a variety of
porphyrin-quinones in excellent yields with aryllithium and vinylic Grignard reagents. From the
mono(3-cyclobutenyl-1,2-dione)-substituted porphyrin, 7, a variety of directly linked monoquinone-
porphyrin dyads were easily synthesized. Substituents could also be introduced at the free meso-
position of 7 by bromination followed by palladium-catalyzed cross-coupling reactions, and additional
porphyrinic monoquinones were then prepared from these starting materials. The vinylogous
squarylporphyrin was converted into a double bond linked porphyrin-quinone via reaction with
phenyllithium followed by thermal rearrangement and oxidation. As a result of the hindered rotation
around the C-C bond between the porphyrin and the quinone, pairs of stable, separable, and
thermally interconvertable atropisomers of porphyrin-quinones were obtained from 5,15-bis(3-
cyclobutenyl-1,2-dione)-10,20-diphenylporphyrin(Zn). The structure of one of the atropisomers was
determined by X-ray crystallography.
In tr od u ction
porphyrins.15-18 Of particular interest are synthetic por-
phyrins bearing moieties that impart unusual biologi-
cal,19 photophysical,20 or electronic properties21 to the
system.
Because of their great potential in health-related1-6
and advanced materials applications,7-9 and as models
for naturally occurring processes,10-14 there is much
interest in novel and efficient routes to substituted
(9) Milgrom, L. R. Porphyrins and the Electronics Revolution.
Porphyrins for the Future; Oxford University Press: Oxford, 1997;
Chapter 7, Section 5, pp 191-243.
(10) Benniston, A. C.; Mackie, P. R.; Harriman, A. Angew. Chem.
1998, 37, 354.
(11) Osuka, A.; Mataga, N.; Okada, T. Pure Appl. Chem. 1997, 69,
797.
(12) Harriman, A.; Sauvage, J .-P. Chem. Soc. Rev. 1996, 41-48.
(13) Kurreck, H.; Huber, M. Angew. Chem. Int. Ed. Engl. 1995, 34,
849-866.
(14) Waseilewski, R. Chem. Rev. 1992, 92, 435.
(15) Hyslop, A. G.; Kellett, M. A.; Therien, M. J . J . Am. Chem. Soc.
1998, 120, 12676.
* To whom correspondence should be addressed. Phone: (404) 727-
6604. Fax: (404) 727-0845. E-mail: Chemlli@emory.edu.
(1) Bonnett, R. Chem. Soc. Rev. 1995, 19-33.
(2) Frank, B.; Nonn, A. Angew. Chem. Int. Ed. Engl. 1995, 34, 1795.
(3) Malik, Z.; Ladan, H.; Nitzan, Y.; Smetana, Z. Proc. SPIE-Int.
Soc. Opt. Eng. 1994, 2078, 305-12.
(4) Li, H.; Fedorova, O. S.; Grachev, A. N.; Trumble, W. R.; Bohach,
G. A.; Czuchajowski, L. Biochim. Biophys. Acta 1997, 1354, 252-260.
(5) Malik, Z.; Hanania, J .; Nitzan, Y. J . Photochem. Photobiol., B
1990, 5, 281-93.
(6) Song, R.; Witvrouw, M.; Schols, D.; Robert, A.; Balzarini, J .; De
Clercq, E.; Bernadou, J .; Meunier, B. Antiviral Chem. Chemother. 1997,
8, 85-97.
(7) LeCours, S. M.; DiMagno, S. G. F.; Therien, M. J . J . Am. Chem.
Soc. 1996, 118, 1854.
(8) Kandasamy, S.; Shetty, S. J .; Puntambekar, P. N.; Srivastava,
T. S.; Kundu, T.; Singh, B. P. J . Porphyrins Phthalocyanines 1999, 3,
81-86.
(16) DiMagno, S. G.; Lin, V. S. Y.; Therien, M. J . J . Org. Chem. 1993,
58, 8, 5983-5993.
(17) DiMagno, S. G.; Lin, V. S.-Y.; Therien, M. J . J . Am. Chem. Soc.
1993, 115, 2513-2515.
(18) Belcher, W. J .; Burrell, A. K.; Wild, K. Y. Tetrahedron 1999,
55, 2401 and references therein.
10.1021/jo9912799 CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/15/2000

3-Cyclobutenyl-1,2-dione-Substituted Porphyrins
J . Org. Chem., Vol. 65, No. 6, 2000 1651
F igu r e 1.
Cyclobutenediones are exceptionally versatile precur-
sors to a broad array of molecular systems.22-27 By
attaching a 3-cyclobutenyl-1,2-dione fragment to a readily
available porphyrin core, the wealth of chemistry ema-
nating from the cyclobutenedione functionality can be
easily brought to porphyrinic molecules, as suggested in
Figure 1. As a specific case in point, porphyrinic cy-
clobutenediones should be effective precursors to struc-
turally diverse porphyrin-quinone architectures. In ad-
dition to the importance of these molecules as model
systems for photosynthetic28,29 electron-transfer stu-
dies,12-14,30 some porphyrin-quinone compounds have
shown potential as anticancer agents,31 and others might
function as unique bimodal catalysts for redox reactions
of small molecules.32 Herein is described an efficient
method for generating 3-cyclobutenyl-1,2-dione substi-
tuted porphyrins and the high-yield conversion of these
into a variety of porphyrinic quinones.
F igu r e 2.
could be readily available from simple porphyrins, such
as 5,15-diphenylporphyrin, using cyclobutenedione chem-
istry.35 Palladium-catalyzed carbon-carbon cross-cou-
pling technology offers a convenient solution to the task,
since it has proven highly effective for the construction
of substituted porphyrinic systems15-17,33,34,36-43 as well
as substituted cyclobutenediones.44-47 Porphyrinic quino-
nes with considerable variation in substitution pattern
and structure should be preparable with this strategy
when coupled with known methods for the selective
bromination and iodination of porphyrins.16,37,48,49
The readily available 5,15-diphenylporphyrin (1) was
selected for initial studies.16,35 5,15-Dibromo-10,20-diphe-
nylporphyrin (4) has been described in the literature:
using 2.2 equiv of NBS, 4 was obtained from 1 as the
exclusive product in 85% yield.16 Bromination of 1 with
1.1 equiv of NBS led to 5-bromo-10,20-diphenylporphyrin
Resu lts a n d Discu ssion
General and efficient synthetic methods that allow the
easy preparation of structurally diverse porphyrinic
quinones are rare.29,33,34 If a 3-cyclobutenyl-1,2-dione unit
could be attached to the porphyrin core, these molecules
(19) Collman, J . P.; Wang, Z. Chemtracts-Org. Chem. 1999, 12, 229-
263.
(20) Piotrowiak, P. Chem. Soc. Rev. 1999, 28, 143-150.
(21) Yang, S.; Seth, J .; Strachan, J .-P.; Gentenann, S.; Kim, D.;
Holten, D.; Lindsey, J . S.; Bocian, D. F. J . Porphyrins Phthalocyanines
1999, 3, 117-147.
(35) Manka, J . S.; Lawrence, D. S. Tetrahedron Lett. 1989, 30, 7341-
7344.
(36) Lin, V. S.-Y.; DiMagno, S. G.; Therien, M. J . Science 1994, 264,
1105-1111.
(37) Boyle, R. W.; J ohnson, C. K.; Dolphin, D. J . Chem. Soc., Chem.
Commun. 1995, 527.
(22) Moore, H. W.; Yerxa, B. R. In Synthetic Utility of Cyclobutene-
diones; Halton, B., Ed.; J AI Press: Greenwich, CT, 1995; Vol. 4, pp
81-162.
(23) Liebeskind, L. S. Tetrahedron Symp. Print 1989, 45, 3053-
3060.
(24) Koo, S.; Liebeskind, L. S. J . Am. Chem. Soc. 1995, 117, 3389-
3404.
(38) Zhou, X.; Chan, K. S. J . Chem. Soc., Chem. Commun. 1994,
2493-2494.
(25) Sun, L.; Liebeskind, L. S. J . Am. Chem. Soc. 1996, 118, 12473.
(26) Paquette, L. A.; Doussot, P. Res. Chem. Intermed. 1996, 22,
767-780.
(27) Ohno, M.; Yamamoto, Y.; Eguchi, S. Synlett 1998, 1167.
(28) Voet, D.; Voet, J . G. Biochemistry, 2nd ed.; J ohn Wiley & Sons:
New York, 1995.
(39) Chan, K. S.; Chan, C. S. Synth. Commun. 1993, 23, 1489-1497.
(40) Chan, K. S.; Zhou, X.; Au, M. T.; Tam, C. Y. Tetrahedron 1995,
51, 3129-3136.
(41) Wagner, R. W.; J ohnson, T. E.; Li, F.; Lindsey, J . S. J . Org.
Chem. 1995, 60, 5266-5273.
(42) Lindsey, J . S.; Wagner, R. W.; J ohnson, T. E. J . Am. Chem.
Soc. 1996, 118, 11166.
(43) Lindsey, J . S.; Prathapan, S.; J ohnson, T. E.; Wagner, R. W.
Tetrahedron 1994, 50, 8941-8968.
(44) Liebeskind, L. S.; Yu, M. S.; Fengl, R. W. J . Org. Chem. 1993,
58, 3543-3549.
(29) Senge, M. O.; Speck, M.; Wiehe, A.; Dieks, H.; Aguirre, S.;
Kurreck, H. Photochem. Photobiol. 1999, 70, 206-216.
(30) Gust, D. E.; Moore, T. A. In Photosynthetic Model Systems;
Mattay, J ., Ed.; Springer-Verlag: Berlin, 1991; Vol. 159, pp 105-151.
(31) Mehta, G.; Muthusamy, S.; Maiya, B. G.; Arounaguiri, S.
Tetrahedron Lett. 1997, 38, 7125-7128.
(45) Liebeskind, L. S.; Yu, M. S.; Yu, R. H.; Wang, J . Y.; Hagen, K.
S. J . Am. Chem. Soc. 1993, 115, 9048-9055.
(46) Liebeskind, L. S.; Fengl, R. W. J . Org. Chem. 1990, 55, 5359.
(47) Liebeskind, L. S.; Wang, J . Tetrahedron Lett. 1990, 31, 4293.
(48) Shultz, D. A.; Gwaltney, K. P.; Lee, H. J . Org. Chem. 1998, 63,
4034-4038.
(32) Grennberg, H.; Faizon, S.; Ba¨ckvall, J . E. Angew. Chem. Int.
Ed. Engl. 1993, 32, 263-264.
(33) Chan, C.-S.; Tse, A. K.-S.; Chan, K. S. J . Org. Chem. 1994, 59,
6084-6089.
(34) Chan, C.-S.; Mak, C. C.; Chan, K. S. Tetrahedron Lett. 1993,
34, 5125-5126.
(49) Milgrom, L. R.; Yahioglu, G. Tetrahedron Lett. 1996, 37, 4069.

1652 J . Org. Chem., Vol. 65, No. 6, 2000
Shi et al.
Sch em e 1a
a
(a) Pd2(dba)3, AsPh3, THF, 55 °C: 85% for 6, 76% for 8. b or c CH2Cl2, Zn(OAc)2 in MeOH, reflux, 98% for 7, 86% for 9.
F igu r e 3. X-ray Structure of compound 9 (C46H32N4O6Zn‚2CH3CO2C2H5). Coordinated solvent molecules are omitted for clarity.
(2; 57%) and 5,15-dibromo-10,20-diphenylporphyrin (4;
11%) (Figure 2).
an efficient coupling of zinc porphyrin 3 with 10, this
catalytic system did not prove useful for the coupling of
5 with 10.
Since electron-withdrawing groups tend to accelerate
many palladium-catalyzed cross-coupling reactions,50-52
free-base porphyrins should undergo palladium-catalyzed
cross-coupling reactions with greater facility than the
more electron-rich metalloporphyrins, at least at the
meso-positions.53 Indeed, compound 4 reacted smoothly
Syn th esis of m eso-Lin k ed Squ a r ylp or p h yr in s.
Following the lead of DiMagno, Lin and Therien,16 who
suggested that free base porphyrins would be problematic
in palladium-catalyzed Stille cross-couplings, the zinc
porphyrins 3 and 5 were treated with 3-isopropoxy-2-tri-
n-butylstannylcyclobutenedione (10) using Pd(PPh3)4 as
the catalyst. Unfortunately, the reaction was slow and
accompanied by the formation of unwanted side products,
and separation of the desired product required careful
chromatography. Although modification of the palladium
precatalyst from Pd(PPh3)4 to Pd2(dba)3/AsPh3 allowed
(50) Milstein, D.; Stille, J . K. J . Am. Chem. Soc. 1979, 101, 4992.
(51) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
(52) Takahashi, S.; Kuroyama, Y.; Sonogashira, K.; Hagihara, N.
Synthesis 1980, 627-630.

3-Cyclobutenyl-1,2-dione-Substituted Porphyrins
J . Org. Chem., Vol. 65, No. 6, 2000 1653
Sch em e 2a
a
(a) Phenyllithium for 11; 2,5-Dimethoxyphenyllithium for 12, THF, -78 °C; (b) NH4Cl-H2O; (c) xylene, reflux; (d) air, room temperature.
Sch em e 3a
a
(a) Xylene reflux; (b) MeI, K2CO3, acetone, room temperature.
with the tri-n-butylstannylcyclobutenedione 10 to give
excellent precursors to porphyrin-quinone dyads. Reac-
tion of 7 with phenyllithium in THF at -78 °C was
complete within a few minutes and gave the 1,2-adduct
11 in 89% yield after aqueous workup and chromatog-
raphy. Thermal rearrangement of 11 followed by air
oxidation of the intermediate hydroquinone gave the
anticipated porphyrin-quinone 13 in 82% yield (Scheme
2). In a similar manner, 12 was isolated in 76% yield from
the reaction of 7 with 2,5-dimethoxyphenyllithium. Rear-
rangement of 12 followed by air oxidation afforded 14 in
57% isolated yield.
the desired product 8 in 76% yield (Scheme 1). Porphyrin
8 was easily purified by trituration with hexanes to
remove all tin-containing compounds, followed by filtra-
tion through a silica gel plug. Metalation of 8 then gave
the desired zinc complex 9. Using the same procedure, 2
was coupled with 10 to give 6 in 84% yield, which was
easily converted into the zinc complex 7 in 98% yield.
An X-ray crystal structure of 9 obtained from a single
crystal grown from hexanes-ethyl acetate showed that
the two squaryl rings are tilted 57.5° from the plane of
the porphyrin ring (Figure 3). Nevertheless, in solution
the B-band and Q-bands of the UV-vis spectra of both 7
and especially 9 are red-shifted compared to 5,15-
diphenylporphyrin, suggesting a fair degree of conjuga-
tion between the squaryl ring and the porphyrin unit.
P or p h yr in -Qu in on e Dya d s fr om Squ a r ylp or p h y-
r in s. As anticipated, the squarylporphyrins proved to be
For unsymmetrically substituted alkoxy(or amino)-
cyclobutenediones, it is known that nucleophilic reagents
add selectively to the carbonyl group adjacent to the
heteroatom substituent.22,23 This precedent notwithstand-
ing, the unknown effect of the porphyrin substituent
made assignment of the regiochemistry of nucleophilic
addition to the porphyrinic cyclobutenedione tenuous. In
an effort to determine the regiochemistry of the 1,2-
adduct unambiguously, compound 16 was synthesized
(53) Fuhrhop, J .-H. In Irreversible Reaction on the Porphyrin
Periphery; Dolphin, D., Ed.; Academic: New York, 1978; Vol. II, p 134.

1654 J . Org. Chem., Vol. 65, No. 6, 2000
Shi et al.
Sch em e 4a
F igu r e 4. NOE connections obtained from the NOESY
spectrum (taken in DMSO-d6 at rt).
and subjected to NMR studies. Scheme 3 illustrates the
two possible regioisomers resulting from addition to the
different carbonyl groups to 7. After addition of o-
tolyllithium to 7, the reaction mixture was quenched with
Ac2O to afford 15. Thermal rearrangement of 15 led to
an intermediate hydroquinone monoacetate that was
unstable in air. Therefore, 15 was thermally rearranged
in carefully degassed xylene, and the intermediate hyd-
roquinone monoacetate was immediately transformed
into the air-stable methyl ether 16 by direct treatment
with K2CO3/MeI.
a
(a) 1-Naphthyllithium, THF, -78 °C; (b) NH4CL-H2O, -78 °C;
(c) xylene, reflux; (d) air, room temperature.
at 60.5 ppm. The unusual upfield displacement to 2.75
ppm of this methoxy group suggests that it sits in the
shielding area of the porphyrin ring, as would be expected
for structure 16. With this signal assigned, NOE experi-
ments then revealed the structure of 16, the results of
which are shown in Figure 4.
1
The analysis of the H NMR spectrum of 16 taken at
A NOE between the singlet at 2.93 ppm and a doublet
from the naphthalene ring at 7.55 ppm indicates that the
signal at 2.93 ppm originates from the naphthylmethyl
substituent. This assignment was confirmed by a COSY
experiment using a modified pulse sequence to enhance
long-range couplings. Cross-peaks between the singlet at
2.93 ppm and both the doublet at 7.55 ppm and a triplet
at 8.13 ppm (protons on the naphthalene ring) clearly
demonstrate that the singlet at 2.93 ppm is the naphth-
ylmethyl group. The unusual downfield chemical shift of
the methyl might be due to the deshielding effect of the
adjacent carbonyl group. Even with all the methyl groups
now assigned, the lack of a NOE between the isopropoxy
methine and the acetyl or methoxy groups prevented
regiochemical assignment without further analysis.
The NOESY spectrum of 16 showed clear NOE con-
nections between naphthyl ring substituents and protons
on the porphyrin ring and on the meso-phenyl substitu-
ents. These connections, in conjunction with the COSY
400 MHz was not routine. The signal from the methine
of the isopropyl group was clearly observable as a heptet
at 3.27 ppm, but a signal for the isopropyl methyl groups
was not found, presumably because of slowed rotation
leading to coalescence of the isopropyl methyl groups on
the 400 MHz NMR time scale.54,55 In contrast, the 1H
NMR spectrum taken at 300 MHz showed a very broad
peak at 0.0 ppm. In addition, the acetoxy, methoxy, and
naphthylmethyl signals could not be unambiguously
assigned, since they all appeared in the same region of
the spectrum (2.46, 2.75, and 2.93 ppm, respectively).
HETCOR, NOESY, and COSY NMR experiments were
needed to assign these signals and determine the struc-
ture of 16.
First, the methoxy protons were easily assigned using
a carbon-proton chemical shift correlation experiment
(HETCOR), which showed a clear cross-peak between the
proton signal at 2.75 ppm and the CH3O- carbon signal
Sch em e 5a
a
Conditions: (a) vinylMgBr, THF, -78 °C to rt; (b) aqueous NH4Cl, -78 °C to rt; (c) DDQ, THF, rt, 5 min.

3-Cyclobutenyl-1,2-dione-Substituted Porphyrins
J . Org. Chem., Vol. 65, No. 6, 2000 1655
F igu r e 5. X-ray structure of compound 24 (C58H40N4O6Zn‚2Et2O. Coordinated solvent molecules are omitted for clarity.
Sch em e 6
isolated yield following the sequence shown in Scheme
2, but without purification of the adduct 11. Similarly,
addition of 1-naphthyllithium to 7 at -78 °C followed by
quenching with NH4Cl-H2O at the same temperature
gave a 1,2-adduct. The crude adduct was heated at reflux
in xylene and then oxidized by air to afford 17 in 78%
isolated yield based on 7 (Scheme 4).
Analogous reactions of monosquarylporphyrin 7 with
alkenyl Grignard reagents provided a route to benzo-
quinone-substituted porphyrins. In contrast to the aryl-
lithium examples described above, where the interme-
diate 1,2-adducts were observed, addition of 1.5 equiv of
vinylmagnesium bromide to a THF solution of 7 directly
generated porphyrin-hydroquinone 19 along with traces
of the porphyrin-quinone 20 (Scheme 5). The porphyrinic
hydroquinone was efficiently oxidized to the correspond-
ing porphyrinic quinone with DDQ.
This overall reaction sequence was successfully ex-
tended to the addition of isopropenylmagnesium bromide
and 1-methyl-1-propenylmagnesium bromide to squaryl-
porphyrin 7. Without isolation, the resulting mixtures
of hydroquinone and quinone were subjected to DDQ
oxidation to produce the porphyrin-quinones 21 and 22
in excellent yields (Scheme 6).
Qu in on e-P or p h yr in -Qu in on e Tr ia d s fr om Bis-
squ a r ylp or p h yr in s. Following the chemistry developed
above for the synthesis of 17, quinone-porphyrin-
quinone triads were synthesized from bissquarylporphy-
rin 9 (Scheme 7). Due to hindered rotation around the
porphyrin-quinone bond, a pair of atropisomeric por-
phyrin-bisquinones was obtained in each case (23/24 and
25/26). These stereoisomers were stable at room temper-
ature, allowing each pair to be readily separated by flash
chromatography.56-58
spectrum, allowed unambiguous assignments of all the
proton signals. The regiochemical arrangement of the
naphthyl substituents was then determined by three
NOE connections: (1) between the methine proton on the
isopropoxy and the â-proton on the porphyrin, (2) be-
tween the methoxy group and the â-proton of the por-
phyrin, and (3) between the methoxy group and the
R-protons of the meso-phenyls. These connections verify
the proximity of the isopropoxy and the methoxy groups,
but not the acetoxy, to the porphyrin and securely
establish the structure of compound 16 as shown in
Figure 4. Therefore, these results unambiguously estab-
lish the regiochemistry of the cyclobutenedione addition
reactions (Schemes 2 and Scheme 3). The lack of NOE
between the methine proton on the isopropyl and the
acetyl methyl is probably due to noncovalent interaction
of the isopropoxy and acetyl that makes the two groups
orient away from each other.55
(54) Sanders, J . K. M.; Hunter, B. K. Modern NMR Spectroscopy. A
Guide for Chemists, 2nd ed.; Oxford University Press: Oxford, 1993.
(55) Sanders, J . K. M.; Hunter, B. K. Modern NMR Spectroscopy. A
Guide for Chemists, 2nd ed.; Oxford University Press: Oxford, 1993.
(56) Kim, J . B.; Adler, A. D.; Longo, F. R. In Synthesis of Porphyrins
from Monopyrroles; Dolphin, D., Ed.; Academic Press: New York, 1978;
Vol. I, p 89.
(57) Gottwald, L. K.; Ullman, E. F. Tetrahedron Lett. 1968, 36,
3071-3074.
(58) Collman, J . P.; Gagne, R. R.; Reed, C.; Halbert, T. R.; Lang,
G.; Robinson, W. J . Am. Chem. Soc. 1975, 97, 1427-1439.
Isolation and purification of the intermediate 1,2-
adducts produced from addition of aryllithium reagents
to 7 was not necessary for the synthesis of porphyrin-
quinones. For example, 13 was synthesized in 93%

1656 J . Org. Chem., Vol. 65, No. 6, 2000
Shi et al.
Sch em e 7a
a
a. Phenyllithium for 23 and 24, 1-naphthyllithium for 25 and 26, THF, -78 °C; b. NH4Cl-H2O, -78 °C; c. cylene, reflux; d. air, room
temperature.
Sch em e 8
An X-ray crystal structure determination of the anti-
isomer 24 was carried out, the ORTEP of which is shown
7 and 9. In fact, the unsubstituted meso-position of
porphyrinic cyclobutenedione derivatives such as 6 can
be further manipulated to introduce functionality at this
position and further modify the structure of the porphyrin
ring. For example, bromination of monosquarylporphyrin
6 gave 27. Free-base porphyrin 27 underwent efficient
Suzuki coupling with 4-methoxyphenylboronic acid to
furnish 28, which was then easily converted into 29, a
precursor to other porphyrin-quinones (Scheme 8).
As a demonstration of the versatility of this chemistry,
29 was also synthesized by changing the order of attach-
ment of the p-anisyl and the squaryl moieties (Scheme
9). Suzuki coupling of free-base porphyrin 2 with 4-meth-
oxyphenylboronic acid gave 30. Bromination of 30 af-
forded 31, which was transformed into 28 by Stille
coupling with tri-n-butylstannylcyclobutenedione 10. The
overall yield from 2 is 70%, compared to 44% for the
procedure depicted in Scheme 8. Metalation of 28 gave
29, which was successfully converted into porphyrinic
quinone 32 in 57% yield. These transformations further
demonstrate that porphyrinic cyclobutenediones are
in Figure 5. Differentiation of the two atropisomers was
1
readily accomplished using the H NMR spectrum: the
two R-protons of the meso-phenyl substituents of the anti-
isomer 24 had the same chemical shift, which is in
agreement with its C2 symmetry property. However, due
to the lower symmetry of the syn-atropisomer 23, these
two protons displayed different chemical shifts. A similar
pair of atropisomers, 25 and 26, was obtained from the
reaction of 1-naphthyllithium and 9 (Scheme 7), and their
structures were determined from the 1H NMR spectra
using the same symmetry arguments made above. Al-
though all of these atropisomers were stable at room
temperature, purified compounds 24 and 26 were readily
converted into an equilibrated anti/syn mixture in an
NMR tube heated at 110 °C in DMSO-d6 for 5 min.
Ad d ition a l F u n ction a liza tion of P or p h yr in -
Qu in on e Dya d s. The above reactions demonstrate a
general principle for achieving structural diversity in the
synthesis of porphyrinic quinones via squarylporphyrins

3-Cyclobutenyl-1,2-dione-Substituted Porphyrins
J . Org. Chem., Vol. 65, No. 6, 2000 1657
Sch em e 9
Sch em e 10
they complement the earlier studies of Therien and co-
workers who carried out the same Stille cross-coupling
using the zinc complex of 5,15-diphenylporphyrin.16
Bromination of 5-vinyl-10,20-diphenylporphyrin (33)
with pyridinium perbromide in ethanol-free chloroform
led exclusively to the trans-bromovinylporphyrin 35 in
44% yield (Scheme 11). The configuration about the
double bond was determined from the coupling constant
(13.6 Hz) between the two olefinic protons, which is
comparable to the J value for trans-bromovinyl-OEP(Ni)
olefin protons (14 Hz).60 In addition, the coupling con-
stants of the derived vinylogous cyclobutenediones (36
and 37; 15.6 Hz) and quinone (38; 16.0 Hz) compounds
clearly show their trans-configurations (Scheme 11). The
Stille reaction was applied to the bromovinylporphyrin
35, giving the desired vinylogous cyclobutenedione-
porphyrin 36 in 77% yield. Treatment with Zn(OAc)2 then
furnished the zinc complex 37 in 91% yield. Upon
reaction of 37 with phenyllithium, the double bond linked
porphyrin-quinone 38 was produced in 46% yield using
the same protocol discussed above. Attempts to extend
this chemistry to porphyrins attached to cyclobutenedi-
ones by way of a C-C triple bond linker have been
unsuccessful thus far.
readily accessible and versatile precursors to a variety
of porphyrinic quinones.
Vin ylogou s Squ a r ylp or p h yr in s a n d P or p h yr in -
Qu in on es. Porphyrinic quinones with aromatic spacers
between the porphyrin and quinone rings are relatively
easy to synthesize, and many of these compounds are
already known.14,30 An intervening π-system between the
porphyrin and quinone moieties allows their relative
orientation and electronic communication to be tailored,
factors that have recently proven vital for electron-
transfer studies.59 For the current study, 5-vinyl-10,20-
diphenylporphyrins were targeted as precursors to double
bond linked porphyrin-quinone compounds. To that
effect, free-base bromoporphyrins 2 and 4 were easily
coupled with vinyltri-n-butyltin and gave products 33 and
34 in 89% and 90% isolated yields, respectively (Scheme
10). These results reinforce the effectiveness of free-base
porphyrins as substrates for Stille coupling reactions, and
Sp ectr oscop y. The visible spectroscopic data of the
zinc metalated cyclobutenedione porphyrins are shown
in Table 1.61 In the solid-state geometries of various 5,-
15-diphenylporphyrin derivatives,16,17,62 as well as for
compounds 9 and 24, the large dihedral angles observed
between meso-substitutents and the porphyrin ring
would suggest weak conjugation between the porphyrin
ring and the attached chromophores.63 Nevertheless,
strong B- and Q-band red shifts are observed relative to
these of 5,15-diphenylporphyrin(Zn) (B-band, 411.0 nm;
(60) Arnold, D. P.; J ohnson, A. W.; Mahendran, M. J . Chem. Soc.,
Perkin Trans. 1 1978, 366-370.
(61) Gouterman, M. In Optical Spectra and Electronic Structure of
Porphyrins and Related Rings; Dolphin, D., Ed.; Academic: New York,
1978; Vol. III, pp 1-165.
(62) Arnold, D. P.; Bott, R. C.; Eldridge, H.; Elms, F. M.; Smith, G.;
Zojaji, M. Aust. J . Chem. 1997, 50, 495.
(59) Davis, W. B.; Svec, W. A.; Ratner, M. A.; Wasielewski, M. R.
Nature 1998, 396, 60-63.
(63) Imahori, H.; Higuchi, H.; Matsuda, Y.; Itagaki, A.; Sakai, Y.;
Ojima, J .; Sakata, Y. Bull. Chem. Soc. J pn. 1994, 67, 2500.

1658 J . Org. Chem., Vol. 65, No. 6, 2000
Shi et al.
Sch em e 11
Ta ble 1. Visible Sp ectr a of th e P or p h yr in ic
Cyclobu ten ed ion es
significant red shifts and intensification of the longer
wavelength absorption relative to the lower wavelength
peak.
B-band
λ max (nm)
Q-bands
λ max (nm)
The visible absorption spectral data of the porphyrinic
quinones are shown in Table 2. In contrast to the
monosquarylporphyrins, a single meso-linked quinone
moiety had little effect on the wavelength and intensity
of the visible absorptions, compared to 5,15-diphenylpor-
phyrin(Zn). On the other hand, the absorption of the
bisquinone-porphyrins was significantly affected. The
syn-compounds 23 and 25 gave the simplest spectra,
since the longest wavelength Q-bands disappeared. The
anti-compounds 24 and 26 displayed both Q-bands;
however, they were red-shifted compared to those of 5,-
15-diphenylporphyrin. For compound 24 the Q-bands
were red-shifted by 21.0 and 10.0 nm, whereas for 26 they
were red-shifted by 14.5 and 9.5 nm.
Introduction of a double bond between the quinone and
the porphyrin ring significantly changed the absorption
of the porphyrin. For compound 38, the Q-bands ap-
peared at 633.5 and 554.5 nm, corresponding to red shifts
of 54.5 and 11.5 nm, respectively, relative to the 5,15-
diphenylporphyrin(Zn). As would be predicted on the
basis of steric arguments, the spacer leads to better
orbital interaction between the porphyrin and the quino-
ne, compared to directly linked porphyrinic quinones.
The effects of the absorption shifts can be seen with
the naked eye. All the cyclobutenedione-porphyrins are
green in solution and dark green in the solid state, while
the typical color of the directly linked porphyrinic quino-
nes is red.
compd
log ꢀ
log ꢀ
7
430.0
438.0
440.0
5.17
597.5
554.5
617.0
564.0
627.5
570.0
629.0
562.5
3.92
4.00
4.20
4.08
4.20
3.79
4.36
4.04
29
9
5.38
5.23
37
455.5
431.0
5.23
5.14
Q-bands, 543.0 and 579.0 nm), which suggests a reason-
able degree of conjugation between the chromophores in
solution.
Introduction of a double bond between the 3-cyclobute-
nyl-1,2-dione moiety and the porphyrin ring (37) pro-
duced a 31.5 and 19.5 nm red shift of the two Q-bands,
relative to the absorptions of the monosquaryl porphyrin
7. The change of the B-band of 37 is even more profound.
Instead of showing a single sharp absorption, as did 7,
splitting of the band is clearly observable (Figure 6, 455.5
and 431.0 nm). Very few monomeric porphyrins show
splitting of the B-band.36,63-65 Although the B-band and
Q-band absorptions of 37 were slightly blue-shifted (by
7 and 6 nm, respectively) upon a solvent change from
methylene chloride to acetonitrile (Figure 6), it appears
that aggregation phenomena are not responsible for the
observed band splitting, since the pattern of the spectra
taken in THF and methylene chloride was essentially the
same.66 B-band splitting of monomeric porphyrins which
have an electron-withdrawing group at a meso-position
(NO2,63 CHO,65 and triple bonds36) has been attributed
to charge transfer.63,64 However, many compounds that
share the above structural features do not show this split
B-band absorption,65 so it is difficult to attribute the
splitting to charge transfer. Whatever the cause, these
data clearly demonstrate that an intervening double bond
greatly facilitates the electronic interaction between the
porphyrin ring and 3-cyclobutenyl-1,2-dione, leading to
Con clu sion s
Stille coupling of 3-isopropoxy-2-tri-n-butylstannylcy-
clobutenedione with bromoporphyrins and bromovinylpor-
phyrins produces porphyrinic cyclobutenediones. The zinc
complexes of these porphyrinic cyclobutenediones proved
to be excellent and versatile precursors to porphyrinic
quinones. Treatment of porphyrinic cyclobutenediones
with a variety of aryllithium and vinylic Grignard
reagents followed by aqueous workup, thermal rear-
rangement, and oxidation gave the corresponding por-
phyrinic quinones in high yields. Therefore, a wide
variety of porphyrinic quinones can now be easily syn-
(64) Arnold, D. P.; J ames, D. A. J . Org. Chem. 1997, 62, 3460.
(65) Yeung, M.; Ng, A. C. H.; Drew, M. G. B.; Vorpagel, E.; Breitung,
E. M.; McMahon, R. J .; Ng, D. K. P. J . Org. Chem. 1998, 63, 7143-
7150.
(66) Anderson, H. L. Inorg. Chem. 1994, 33, 972.

3-Cyclobutenyl-1,2-dione-Substituted Porphyrins
J . Org. Chem., Vol. 65, No. 6, 2000 1659
F igu r e 6. UV-vis spectrum of compound 37 (solid line in THF; broken line in CH2Cl2; dotted line in acetonitrile).
Ta ble 2. UV-Vis Absor p tion s of th e P or p h yr in -Qu in on e
from the corresponding aryl bromides and tert-butyllithium
following literature procedures.69
Com p ou n d s
Two-dimensional spectra were acquired on an INOVA-400
(400 MHz H) spectrometer using the Varian standard micro-
B-band
λ max (nm)
Q-bands
λ max (nm)
1
compd
log ꢀ
log ꢀ
program at room temperature. A total of 128 t1 increments
and 1024 t2 data points were employed. For COSY with τ (0
or 0.2 s) (pulse sequence: D1-90-D0-45-τ-FID), four scans
were collected for each t1 FID, and the spectrometer time was
about 10 and 20 min, respectively. For NOESY (pulse se-
quence: D1-90-D0-90-mix-90-FID), 48 scans were ac-
cumulated for each t1 FID. Two experiments with mixing times
of 0.7 and 0.5 s and relaxation delays of 2 and 3 s, respectively,
were performed for compound 16. The typical spectrometer
time was about 10 h. For the carbon-proton chemical shift
correlation (HETCOR) spectrum of compound 16, a total 128
t1 increments were accumulated, and 176 scans were collected
for each t1 FID. The spectrometer time was about 12 h. DMSO-
d6 was used as the solvent for the 2D NMR experiments of
16, and 2 drops of D2O was added to shift the water peak away
from the signal of the methine of the isopropyl group.
Sta r tin g Ma ter ia ls. 5,15-Diphenylporphyrin (1),16 5,15-
dibromo-10,20-diphenylporphyrin (4),16 5,15-dibromo-10,20-
diphenylporphyrin(Zn) (5),16 and 3-isopropoxy-2-tri-n-butyl-
stannylcyclobutenedione (10)46 were synthesized by literature
methods.
5-Br om o-10,20-d ip h en ylp or p h yr in (2).62 5,15-Diphe-
nylporphyrin (1) (3.0 g, 6.48 mmol, 1.00 equiv) and NBS (1.26
g, 7.13 mmol, 1.1 equiv) in methylene chloride (500 mL) were
stirred at room temperature for 6.5 h. The volume of the
solvent was reduced to 150 mL to precipitate 4, which was
filtered. The filtrate was dried, and the crude product was
separated by flash chromatography (silica gel, 5 × 15 cm,
hexanes-methylene chloride, gradient from 10:1 to 4:1, v/v),
giving the known product 262 (2.01 g, 3.72 mmol, 57%) as a
brown solid of sufficient purity for subsequent reactions. Anal.
Calcd for C32H21N4Br: C, 70.99; H, 3.91; N, 10.35; Br, 14.76.
Found: C, 71.06; H, 3.93; N, 10.35; Br, 14.67. In addition,
dibromo compound 4 (0.47 g, 0.75 mmol, 11%) and starting
material (0.22 g, 0.48 mmol, 7%) were obtained from the
chromatography.
13
414.0
5.14
584.0
546.0
505.0
450.5
546.5
506.5
546.0
493.0
548.0
548.0
548.0
554.0
600.0
553.5
550.0
593.5
553.0
633.5
554.5
4.83
5.65
5.11
5.41
5.14
4.97
5.49
4.97
4.70
4.76
4.71
5.08
4.60
5.00
4.95
4.66
5.14
4.39
4.43
14
17
411.0
414.0
5.52
5.89
20
21
22
23
24
417.0
416.5
416.5
419.5
419.5
5.66
5.66
5.74
5.53
5.45
25
26
419.0
420.0
5.38
5.59
38
420.5
5.72
thesized. Efforts are underway to use the chemistry
described within this paper to synthesize novel squarylpor-
phyrin-derived compounds, such as those depicted in
Figure 1.
Exp er im en ta l Section
Gen er a l Met h od s. Tetrahydrofuran (THF) was sparged
with nitrogen and then dried over 4 Å molecular sieves. The
water content was e50 ppm as measured by a Model 447
Coulomatic K-F Titrimeter. Other solvents for reactions,
extractions, and chromatography were used as received from
the commercial sources. Silica gel (silica gel 60, 230-400 mesh)
for flash and Baeckstrom67 chromatography (medium pressure)
was purchased from EM Science. Silica gel analytical thin-
layer chromatography plates with F-254 indicator were ob-
tained from Merck and were visualized with UV light, phos-
phomolybdicacid solution,or iodine.Meltingpoints (uncorrected)
were determined using a Thomas-Hoover capillary oil-immer-
sion melting point apparatus. Phenyllithium and tert-butyl-
lithium in hexanes were obtained from commercial sources and
titrated with diphenyl ditelluride68 and diphenyl acetic acid,
respectively, before use. Aryllithium reagents were prepared
5-Br om o-10,20-d ip h en ylp or p h yr in (Zn ) (3).36 5-Bromo-
10,20-diphenylporphyrin (2) (541 mg, 1 mmol, 1.00 equiv) in
methylene chloride (200 mL) and zinc acetate (400 mg, 2.1
mmol, 2.1 equiv) in methanol (150 mL) were stirred at room
temperature for 3 h and then washed three times with water
to remove excess Zn(OAc)2. After evaporation of the solvent,
the product 3 was obtained as a red solid (592 mg, 98%) of
sufficient purity for the subsequent reactions. TLC (silica gel,
hexanes-methylene chloride (1:1)): Rf )0.5. Mp >250 °C
(hexanes-THF). 1H NMR (CDCl3, 300 MHz): δ 10.23 (s, 1 H),
9.82 (d, J ) 4.5 Hz, 2 H), 9.36 (d, J ) 4.8 Hz, 2 H), 9.04 (dd,
(67) Purchased from Baeckstro¨m SEPARO AB, Larsbergsva¨gen 24,
S-181 39 Lindingo¨, Sweden.
(68) Aso, Y.; Yamashita, H.; Otsubo, T.; Ogura, F. J . Org. Chem.
1989, 54, 5627-5629.
(69) Schlosser, M. In Organoalkali Reagents; Schlosser, M., Ed.;
J ohn Wiley & Sons: Chichester, 1994; pp 1-166.

1660 J . Org. Chem., Vol. 65, No. 6, 2000
Shi et al.
J ) 4.8, 4.5 Hz, 4 H), 8.22 (d, J ) 7.6 Hz, 4 H), 7.78 (m, 6 H).
(CDCl3, 400 MHz): δ 9.15 (d, J ) 5.2 Hz, 4 H), 8.89 (d, J )
4.8 Hz, 4 H), 8.18 (dd, J ) 6.4, 1.2 Hz, 4 H), 7.81 (m, 6 H),
5.89 (sept, J ) 6.0 Hz, 2 H), 1.60 (d, J ) 6.0 Hz, 12 H), -2.35
(s, 2 H). 13C NMR (CDCl3, 100 MHz): δ 198.2, 194.4, 193.9,
180.7, 141.3, 134.4, 128.2, 126.9, 123.2, 104.2, 80.8, 22.9. UV-
vis: λmax (log ꢀ, CH2Cl2) 441.5 (5.65), 588.0 (4.62), 679.0 (4.44)
nm. MS(FAB): m/z 745 (M + Li+) (100). HRMS (FAB): calcd
for C46H34O6N4 Li 745.2638, found 745.2653.
HRMS (FAB): calcd for
602.0092.
C32H19N4BrZn 602.0084, found
P r ep a r a tion of Squ a r ylp or p h yr in s 6-9. 5-(2-Isop r o-
poxycyclobu ten e-3,4-dion yl)-10,20-diph en ylpor ph yr in (6).
The synthesis of this compound is representative of the
preparation of other compounds by the Stille coupling reaction.
To a round-bottomed flask under nitrogen were added 2 (853
mg, 1.58 mmol, 1.00 equiv), 10 (1362 mg, 3.2 mmol, 2.51 equiv),
Pd2(dba)3 (72 mg, 0.079 mmol, 0.05 equiv), triphenylarsine (193
mg, 0.63 mmol, 0.40 equiv), and THF (50 mL). The mixture
was stirred at 55 °C for 42 h, then solvent was removed, and
the residue was triturated with hexanes three times to remove
tin compounds. The crude product was initially purified by
filtration through a silica gel plug (SiO2, 3.5 × 4 cm, hexanes-
methylene chloride (1:1)) to give product that was dissolved
in methylene chloride and precipitated with hexanes. Filtra-
tion gave a dark brown solid (770 mg, 84%). Mp > 250 °C
(hexanes-methylene chloride, diffusion). IR (KBr pellet, cm-1):
3318 (m), 1785 (s),1752 (s). 1H NMR (CDCl3, 400 MHz): δ
10.22 (s, 1 H), 9.29 (d, J ) 4.8 Hz, 2 H), 9.22 (d, J ) 4.8 Hz,
2 H), 9.01 (d, J ) 5.2 Hz, 2 H), 8.94 (d, J ) 4.8 Hz, 2 H), 8.22
(dd, J ) 7.2, 1.6 Hz, 4 H), 7.82 (m, 6 H), 5.86 (sept, J ) 6.0
Hz, 1 H), 1.57 (d, J ) 6.0 Hz, 6 H), -2.76 (s, 2 H). 13C NMR
(CDCl3, 100 MHz): δ 198.2, 194.7, 194.4, 182.1, 141.2, 134.6,
132.4, 131.5, 129.3, 127.9, 126.9, 121.4, 107.8, 101.8, 80.5, 22.9.
UV-vis: λmax (log ꢀ, CH2Cl2) 429.2 (5.23), 521.5 (3.99), 563.0
(4.00), 652.0 (3.36) nm. MS(FAB): m/z 601.2 (74). HRMS
(FAB): calcd for C39H28N4O3 600.2161, found 600.2189. The
corresponding zinc complex was fully characterized, below.
Compound 7 was prepared by insertion of Zn(II) into 6
following the procedure used to prepare compound 3, above:
5-(2-Isopropoxycyclobutene-3,4-dionyl)-10,20-diphenylporphy-
rin (6) (18 mg, 0.03 mmol), methylene chloride (5 mL), zinc
acetate (16 mg, 0.088 mmol), and methanol (5 mL) yielded the
product 7 (19 mg, 98%). Complete characterization is given in
the following description.
5,15-Bis(2-isop r op oxycyclob u t en e-3,4-d ion yl)-10,20-
d ip h en ylp or p h yr in (Zn ) (9). 9 was prepared from 8 following
the procedure for 7, above. A mixture of 5,15-bis(2-isopropoxy-
cyclobutene-3,4-dionyl)-10,20-diphenylporphyrin (8) (212 mg,
0.28 mmol) in methylene chloride (50 mL) and Zn(OAc)2 (183
mg, 1 mmol) in methanol (40 mL) was stirred at reflux
temperature for 1 h, then washed three times with water, and
purified through a plug of silica gel (methylene chloride-ether
(1:1)). Product 9 was obtained as a dark green solid (263 mg,
86%). TLC (silica gel, hexanes-ethyl acetate (2:1)): Rf ) 0.3.
Mp > 250 °C (ethyl acetate). IR (KBr pellet, cm-1): 1781 (s),
1
1752 (s). H NMR (CDCl3): δ 9.47 (d, J ) 4.4 Hz, 4 H), 8.90
(d, J ) 4.8 Hz, 4 H), 8.23 (dd, J ) 7.4, 1.6 Hz, 4 H), 7.9-7.8
(m, 6 H), 5.91 (hept, J ) 6.4 Hz, 2 H), 1.58 (d, J ) 6.4 Hz, 12
H). 13C NMR ((CD3)2CO, 100 MHz): δ 199.9, 196.3, 196.0,
181.6, 152.2, 148.8, 144.1, 135.7, 133.8, 132.5, 129.2, 128.1,
124.4, 106.4, 81.5, 23.6, 14.0. UV-vis: λmax (log ꢀ, CH2Cl2)
444.0 (5.23), 570.0 (3.79), 627.5 (4.20) nm. HRMS (FAB): calcd
for C46H32O6N4Zn 800.1612, found 800.1571.
Con ver sion of Squ a r ylp or p h yr in s in to P or p h yr in ic
Qu in on es 13-26. Rep r esen ta tive P r oced u r e for P r ep a -
r a tion of P or p h yr in -Qu in on e Com p ou n d s. A 1.2 equiv
sample of phenyllithium (0.22 M in THF, 0.81 mL) was added
by a syringe at -78 °C under nitrogen to a solution of 5-(3-
isopropoxycyclobutene-3,4-dionyl)-10,20-diphenylporphyrin-
(Zn) (7) (99 mg, 0.149 mmol, 1.00 equiv) dissolved in THF (10
mL). The reaction mixture immediately turned from green to
red. If the starting material was detected by TLC, additional
10% portion(s) of the lithium reagent were added until the
starting material was consumed. The reaction mixture was
quenched with saturated aqueous ammonium chloride solution
at the same temperature, and then allowed to warm to room
temperature. The mixture was extracted with ether and dried
over sodium sulfate. For compound 11, the crude product was
isolated by column chromatography and characterized. In all
other cases, the crude products were taken up in xylene and
heated at 150 °C with stirring for 15 min to 3 h. The solution
was then stirred overnight under air. Xylene was distilled off
under vacuum, and the crude product was isolated by flash
column chromatography to obtain the desired product.
1-P h e n yl-3-(10,20-d ip h e n ylp or p h yr ozin c)-4-on e cy-
clobu ten e-1-ol (11). 5-(2-Isopropoxycyclobutene-3,4-dionyl-
10,20-diphenylporphyrin(Zn) (7) (99 mg, 0.149 mmol, 1.00
equiv), THF (10 mL), and phenyllithium (1.2 equiv, 0.22 M,
0.75 mL) yielded a purple solid product (99 mg, 0.133 mmol,
89%). TLC (silica gel, hexanes-ethyl acetate (3:2)): Rf ) 0.70.
Chromatographic purification (flash column, silica gel, 2 × 12
cm, hexanes-acetone (3:1)). Mp > 250 °C (methylene chloride-
hexanes, diffusion procedure). IR (KBr pellet, cm-1): 3500 (s),
1742 (s), 1599 (s). 1H NMR (CDCl3, 400 MHz): δ 10.08 (s, 1
H), 9.35 (d, J ) 4.0 Hz, 2 H), 9.25 (d, J ) 4.4 Hz, 2 H), 8.94 (d,
J ) 4.4 Hz, 2 H), 8.86 (d, J ) 4.4 Hz, 2 H), 8.10 (d, J ) 6.8 Hz,
2 H), 7.96 (d, J ) 7.2 Hz, 3 H), 7.70 (t, J ) 4.0 Hz, 3 H), 7.61
(br s, 1 H), 7.55 (t, J ) 8.0 Hz, 2 H), 7.45 (t, J ) 7.6 Hz, 1 H),
4.80 (sept, J ) 6.0 Hz, 1 H), 4.60 (br s, 1 H), 1.13 (d, J ) 6.0
Hz, 3 H), 0.91 (d, J ) 6.0 Hz, 3 H). 13C NMR (CDCl3, 100
MHz): δ 150.2, 149.8, 149.4, 148.9, 142.3, 137.4, 134.5, 134.3,
132.9, 132.4, 131.8, 130.3, 129.3, 129.0, 128.6, 127.4, 126.4,
126.1, 120.7, 106.8, 104.2, 93.1, 79.2, 65.6, 22.4, 22.1, 15.1.
UV-vis: λmax (log ꢀ, THF) 422.0 (5.52), 553.8 (4.08), 593.8
(3.54) nm). MS(FAB): m/z 740. HRMS (FAB): calcd for
5-(2-Isop r op oxycyclob u t en e-3,4-d ion yl)-10,20-d ip h e-
n ylp or p h yr in (Zn ) (7). 7 was prepared by the coupling
reaction of compound 3 with 10. 5-Bromo-10,20-diphenylpor-
phyrin(Zn) (3) (22 mg, 0.036 mmol, 1.00 equiv), 10 (43 mg,
0.100 mmol, 2.78 equiv), Pd2(dba)3‚CHCl3 (7 mg, 0.007 mmol,
0.19 equiv), triphenylarsine (6 mg, 0.018 mmol, 0.50 equiv),
and THF (5 mL) were heated at 60 °C with stirring for 3 d. A
dark green solid (18 mg, 0.027 mmol, 75%) was obtained after
chromatography (flash chromatography, silica gel, 2 × 12 cm,
hexanes-ethyl acetate, gradient). TLC (silica gel, hexanes-
ethyl acetate: (5:2)): Rf ) 0.4. Mp > 250 °C (hexanes-ethyl
acetate, diffusion). IR (KBr pellet, cm-1): 1783 (s), 1750 (s),
1
1732 (s), 1566 (s). H NMR ((CD3)2CO, 400 MHz): δ 10.37 (s,
1 H), 9.47 (d, J ) 4.8 Hz, 2 H), 9.44 (d, J ) 4.4 Hz, 2 H), 8.97
(d, J ) 4.4 Hz, 2 H), 8.95 (d, J ) 4.4 Hz, 2 H), 8.24 (dd, J )
7.2, 2.4 Hz, 4 H), 7.88-7.80 (m, 6 H), 5.89 (hept, J ) 6.4 Hz,
1H), 1.57 (d, J ) 6.0 Hz 6H). 13C NMR ((CD3)2CO, 100 MHz):
δ 199.7, 196.3, 182.6, 152.0, 151.2, 151.0, 148.7, 144.2, 135.7,
133.7, 133.7, 133.3, 131.8, 128.9, 128.0, 122.8, 109.7, 81.2, 23.6.
UV-vis: λmax (log ꢀ, CH2Cl2) 430.0 (5.17), 554.5 (4.00), 597.5
(3.92) nm. MS(FAB): m/z 669.2 (8.8). HRMS (FAB): calcd for
M + H+ C39H26N4O3Zn 662.1296, found M + H+ 662.1275.
Anal. Calcd for C39H25N4O3Zn: C, 70.65; H, 3.80; N, 8.45.
Found: C, 70.46; H, 4.18; N, 8.45.
5,15-Bis(2-isop r op oxycyclob u t en e-3,4-d ion yl)-10,20-
d ip h en ylp or p h yr in (8). Compound 8 was prepared following
the procedure used to make compound 6, above. 5,15-Dibromo-
10,20-diphenylporphyrin (4) (451 mg, 0.726 mmol, 1.00 equiv),
10 (1.40 g, 3.250 mmol, 4.48 equiv), Pd2(dba)3‚CHCl3 (151 mg,
0.146 mmol, 0.20 equiv), triphenylarsine (193 mg, 0.629 mmol,
0.87 equiv), and THF (50 mL) were stirred together at 50 °C
for 17 h. After removal of solvent, the crude material was
triturated with hexanes and then filtered through a plug of
silica gel under vacuum with 1:1 hexanes-CH2Cl2 to remove
impurities. Elution with CH2Cl2 then gave the product as a
dark green solid (418 mg, 0.566 mmol, 78%). TLC (silica gel,
hexanes-acetone (3:1)): Rf ) 0.2. Mp > 250 °C (hexanes/THF).
IR (KBr pellet, cm-1): 3317 (m), 1786 (s), 1754 (s). 1H NMR
C
C
45H32N4O3Zn 740.1766, found 740.1772. Anal. Calcd for
45H32N4O3Zn‚H2O: C, 71.10; H, 4.51; N, 7.37. Found: C,
71.46; H, 4.63; N, 7.01.
5-(2-Isop r op oxyln a p h th oqu in on yl)-10,20-d ip h en ylp or -
p h yr in (Zn ) (13). With stirring, compound 11 (37 mg, 0.050
mmol, 1.00 equiv) in xylene (10 mL) was heated at reflux for

3-Cyclobutenyl-1,2-dione-Substituted Porphyrins
J . Org. Chem., Vol. 65, No. 6, 2000 1661
1.5 h and then left at room temperature for 3 h under air. After
the xylene was removed under vacuum, the crude product was
purified by column chromatography (silica gel, hexanes-
acetone (2:1)), giving a purple solid (30 mg, 0.041 mmol, 82%).
TLC (silica gel, hexanes-acetone (3:1)): Rf ) 0.3. Mp 225 °C
dec (hexanes-methylene chloride, diffusion). IR (KBr pellet,
cm-1): 1671 (s), 1598 (s). 1H NMR (CDCl3, 400 MHz): δ 10.28
(s, 1 H), 9.40 (d, J ) 4.8 Hz, 2 H), 9.17 (d, J ) 4.8 Hz, 2 H),
9.08 (d, J ) 4.4 Hz, 2 H), 9.00 (d, J ) 4.8 Hz, 2 H), 8.43 (dd,
J ) 7.6, 1.2 Hz, 1 H), 8.32 (m, 2 H), 8.25 (dd, J ) 7.2, 1.6 Hz,
1 H), 8.18 (br d, J ) 7.2 Hz, 2 H), 7.91 (dt, J ) 7.2, 1.6 Hz, 1
H), 7.88 (dt, J ) 7.2, 1.2 Hz, 1 H), 7.80 (m, 6 H), 4.57 (hept, J
) 6.0 Hz, 1 H), 0.55 (d, J ) 6.0 Hz, 6 H). 13C NMR (CDCl3,
100 MHz): δ 187.0, 182.9, 158.8, 150.3, 150.0, 149.5, 148.9,
142.7, 134.7, 134.4, 134.4, 133.6, 132.8, 132.4, 131.7, 130.2,
127.4, 127.1, 126.7, 126.6, 126.5, 120.5. 106.7, 76.5, 66.0, 65.7,
22.9. UV-vis: λmax (log ꢀ, Et2O) 414.0 (5.14), 450.5 (5.41), 505.0
(5.11), 546.0 (5.65), 584.0 (4.83) nm. MS(FAB): m/z 738. HRMS
(FAB): calcd for C45H30N4O3Zn 738.1609, found 738.1609.
5-(2-Isop r op oxyln a p h th oqu in on yl)-10,20-d ip h en ylp or -
p h yr in (Zn ) (13) fr om 7 w ith ou t P u r ifica tion of In ter m e-
d ia te 11. The crude product from the aqueous workup of the
reaction of 7 (66 mg, 0.099 mmol, 1.00 equiv) in THF (10 mL)
with phenyllithium (1.47 equiv, 0.21 M, 0.70 mL) was taken
up by xylene and refluxed for 20 min and then stirred at room
temperature overnight under air. Xylene was evaporated
under vacuum, and product 13 was isolated by column
chromatography (SiO2, 2.5 × 5 cm, hexanes-ether (5:1)) as a
purple solid (69 mg, 0.093 mmol, 93%).
iodomethane (45 mg, 0.32 mmol) were added to the mixture
by a syringe, and the reaction mixture was stirred at room
temperature overnight. After the reaction was complete (judged
by TLC), the potassium carbonate was filtered off and the
crude product was isolated by preparative TLC (SiO2, 20 ×
20 cm, 0.5 mm, hexanes-ether (3:1)), producing the desired
compound 16 as a red solid (4 mg, 66%). TLC (silica gel,
hexanes-acetone (3:2)): Rf ) 0.5. Mp > 250 °C (methylene
chloride-hexanes, diffusion). IR (KBr pellet, cm-1): 1768 (m),
1
1733 (m), 1653 (m), 1635 (m). H NMR (CDCl3, 400 MHz): δ
10.27 (s, 1 H), 9.40 (d, J ) 4.4 Hz, 2 H), 9.09 (d, J ) 4.4 Hz,
4 H), 9.02 (d, J ) 4.4 Hz, 2 H), 8.26 (m, 5 H), 7.78 (br s, 6 H),
7.49 (d, J ) 2.8 Hz, 2 H), 3.28 (hept, J ) 6.4 Hz, 1 H), 3.02 (s,
3 H), 2.79 (s, 3 H), 2.46 (s, 3 H). 13C NMR (CDCl3, 100 MHz):
δ 169.4, 154.7, 150.6, 150.2, 150.2, 149.3, 147.9, 142.6, 134.6,
132.9, 132.8, 132.3, 131.7, 130.7, 128.8, 128.4, 127.5, 126.5,
125.5, 121.7, 120.4, 111.1, 106.6, 75.8, 61.5, 23.7, 21.7, 21.5.
UV-vis: λmax (log ꢀ, CH2Cl2) 417 (5.68), 548 (4.27), 586 (3.37)
nm. MS(FAB): m/z 810 (100). HRMS (FAB): calcd for
C
49H38N4O4Zn 810.2185, found 810.2189.
5-(2-Isopr opoxy-3,10-ph en an th r oqu in on yl)-10,20-diph e-
n ylp or p h yr in (Zn ) (17). 1-Naphthyllithium (0.5 mL, 0.43 M
in THF, 1.1 equiv) and 5-(2-isopropoxycyclobutene-3,4-dionyl)-
10,20-diphenylporphyrin(Zn) (7) (132 mg, 0.199 mmol) in THF
(12 mL) gave a 1,2-adduct, which was isolated and then heated
in refluxing xylene for 30 min. After air oxidation and isolation
(flash column, silica gel, 2 × 9 cm, hexanes-ether (25:7)), the
product 17 was obtained (123 mg, 0.156 mmol, 78%) as a
purple solid. TLC (silica gel, hexanes-ether (1:2), v/v): Rf )
0.3. Mp > 250 °C (methylene chloride-hexanes, diffusion). IR
(KBr pellet, cm-1): 1663 (s), 1599 (s). 1H NMR (CDCl3, 400
MHz): δ 10.28 (s, 1 H), 9.71 (d, J ) 8.8 Hz, 1 H), 9.41 (d, J )
4.4 Hz, 2 H), 9.23 (d, J ) 4.4 Hz, 2 H), 9.09 (d, J ) 4.4 Hz, 2
H), 9.02 (d, J ) 4.4 Hz, 2 H), 8.33-8.18 (m, 6 H), 7.96 (d, J )
8.0 Hz, 1 H), 7.86-7.68 (m, 8 H), 4.48 (hept, J ) 6.0 Hz, 1 H),
0.65 (d, J ) 6.0 Hz, 6H). 13C NMR (CDCl3, 100 MHz): δ 185.2,
150.3, 150.1, 149.5, 142.6, 136.4, 135.4, 134.7, 134.4, 132.9,
132.4, 131.8, 130.3, 130.2, 128.9, 128.6, 127.8, 127.5, 126.6,
126.5, 122.7, 120.6, 106.7, 76.4, 65.7, 22.7. UV-vis: λmax (log
ꢀ, Et2O) 414.0 (5.89), 493.3 (4.97), 546.0 (5.49) nm. MS(FAB):
m/z 789; HRMS (FAB): calcd for C49H32O3N4Zn 788.1765,
found 788.1735.
5,15-Dip h en yl-10-(2-isop r op oxy-3,6-h yd r oxyben zen e)-
p or p h yr in (Zn ) (19) a n d 5,15-Dip h en yl-10-(2-isop r op oxy-
3,6-ben zoqu in on e)p or p h yr in (Zn ) (20). Vinylmagnesium
bromide (0.22 mL, 1.0 M in THF, 0.22 mmol) was added
dropwise to a solution of 5-(2-isopropoxycyclobutene-3,4-dio-
nyl)-10,20-diphenylporphyrin(Zn) (7) (100 mg, 0.15 mmol) in
THF (20 mL) in a 50 mL round-bottomed flask under nitrogen
at -78 °C. The reaction mixture was allowed to warm to room
temperature and then recooled to -78 °C, and a few drops of
aqueous ammonium chloride were added. After being warmed
to room temperature, the reaction mixture was partitioned
between water-dichloromethane, then the organic layer was
dried over anhydrous sodium sulfate, and the solvent was
evaporated. Primary purification of the crude product by flash
column chromatography (silica gel, 2.5 × 10 cm) using 10-
20% THF-hexanes as the eluant to afford hydroquinone 19
(83 mg, 80%) and quinone 20 (18 mg, 17%), both as red solids.
The hydroquinone could not be completely separated from the
quinone.
5-(2-Isop r op oxy-5,8-d im eth oxyn a p h th oqu in on yl)-10,-
20-d ip h en ylp or p h yr in (Zn ) (14). From 5-(2-isopropoxycy-
clobutene-3,4-dionyl)-10,20-diphenylporphyrin(Zn) (7) (66 mg,
0.1 mmol), THF (6 mL), and 2,5-dimethoxyphenyllithium (0.11
mmol, 1.1 equiv, 0.31 M in THF, 0.35 mL) was obtained
product 12 (61 mg, 76%), which was isolated by column
chromatography (silica gel, 2 × 12 cm, solvent: hexanes-
acetone (10:1 to 5:2)). This product was used directly for the
following thermolysis reaction without full characterization.
Compound 12 (73 mg, 0.091 mmol, 1.00 equiv) in xylene (15
mL) was heated at reflux for 3 h, and then stirred at room
temperature overnight under air to give 14 as a purple solid
(42 mg, 0.052 mmol, 57%), which was isolated by column
chromatography (flash column, silica gel, 2 × 9 cm, hexanes-
acetone gradient). TLC (silica gel, hexanes-acetone (3:1)): Rf
) 0.2). Mp > 250 °C (methylene chloride-hexanes, diffusion).
1
IR (KBr pellet, cm-1): 1667 (s). H NMR (CDCl3, 400 MHz):
δ 10.07 (s, 1 H), 9.26 (d, J ) 4.4 Hz, 2 H), 9.19 (d, J ) 4.8 Hz,
2 H), 9.02 (d, J ) 4.4 Hz, 2 H), 8.99 (d, J ) 4.8 Hz, 2 H), 8.30
(dd, J ) 4.4, 2.4 Hz, 2 H), 8.17 (dd, J ) 8.0, 1.2 Hz, 2 H), 7.78
(m, 6 H), 7.33 (s, 2 H), 4.65 (sept, J ) 6.0 Hz, 1 H), 4.06 (s, 3
H), 3.77 (s, 3 H), 0.64 (d, J ) 6.0 Hz, 6 H). 13C NMR (CDCl3,
100 MHz): δ 186.5, 182.2, 158.6, 153.8, 150.1, 150.0, 149.2,
149.1, 142.7, 134.7, 134.4, 133.4, 132.7, 132.2, 131.6, 130.5,
127.4, 126.5, 126.5, 121.7, 121.6 121.3, 120.3, 119.5, 106.4,
75.8, 65.6, 57.0, 56.9, 29.7, 22.8. UV-vis: λmax (log ꢀ, Et2O)
411.0 (5.52), 506.5 (4.59), 546.5 (5.14) nm. MS(FAB): m/z
799.8. HRMS (FAB): calcd for
found: 798.1799.
C47H34N4O5Zn 798.1821,
5-(2- Isopr opoxy-3- a cetoxy-5-m eth yl-10-m eth oxyn a ph -
th yl)-10,20-d ip h en ylp or p h yr in (Zn ) (16). 2-Methylphenyl-
lithium (0.21 M in THF, 0.57 mL, 1.2 equiv) was added
dropwise under nitrogen to a 25 mL round-bottomed flask
containing 5-(2-isopropoxycyclobutene-3,4-dionyl)-10,20-diphe-
nylporphyrin(Zn) (7) (66 mg, 0.1 mmol) in THF (6 mL) at -78
°C. After 10 min the reaction was quenched with acetic
anhydride (10 equiv) at -78 °C and then stirred at room
temperature for 1 h. After removal of the solvent and chro-
matography (flash, SiO2, 2 × 10 cm, hexanes-acetone (6:1)),
the intermediate product 15 was obtained as a red solid (77
mg, 65%). A portion of compound 15 (6 mg, 0.076 mmol) was
dissolved in xylene (5 mL) and carefully degassed using a
freeze-thaw procedure and then heated at reflux under
nitrogen atmosphere for 2 h. After the xylene was removed
under vacuum, potassium carbonate (20 mg, 0.14 mmol) was
added immediately under nitrogen. Acetone (3 mL) and
P r od u ct 19. TLC (silica gel, THF-hexanes (1:3)): Rf ) 0.23.
1
IR (KBr pellet, cm -1): 3535 (w). H NMR (CDCl3, 400 MHz):
δ 10.28 (s, 1 H), 9.40 (d, J ) 4.8 Hz, 2 H), 9.10 (d, J ) 4.4 Hz,
2 H), 9.02 (s, 4 H), 8.27-8.30 (m, 2 H), 8.19-8.24 (m, 2 H),
7.75-7.84 (m, 6 H), 7.20 (d, J ) 8.8 Hz, 1 H), 6.89 (d, J ) 8.8
Hz, 1 H), 5.61 (s, 1 H), 4.68 (s, 1 H), 2.86 (hept, J ) 6 Hz, 1
H), 0.14 (d, J ) 6 Hz, 6 H). HRMS (FAB): calcd for C41H30N4O3-
Zn 690.1609, found 690.1635.
P r od u ct 20. TLC (silica gel, THF-hexanes (1:3)): Rf ) 0.39.
Mp > 250 °C (ethyl acetate-hexanes, diffusion). IR (KBr
pellet, cm-1): 1673 (m), 1651 (m). 1H NMR (CDCl3, 400
MHz): δ 10.23 (s, 1 H), 9.37 (d, J ) 4.4 Hz, 2 H), 9.11 (d, J )
4.4 Hz, 2 H), 9.07 (d, J ) 4.8 Hz, 2 H), 9.02 (d, J ) 4.8 Hz, 2
H), 8.28-8.33 (m, 2 H), 8.18-8.23 (m, 2 H), 7.75-7.84 (m, 6

1662 J . Org. Chem., Vol. 65, No. 6, 2000
Shi et al.
H), 7.18 (d, J ) 10.4 Hz, 1 H), 7.13 (d, J ) 10.4 Hz, 1 H), 4.27
(hept, J ) 6.0 Hz, 1 H), 0.51 (d, J ) 6.0 Hz, 6 H). 13C NMR
(CDCl3, 100 MHz): δ 189.8, 184.7, 150.6, 150.3, 149.8, 149.0,
142.7, 137.2, 135.9, 134.9, 134.7, 133.2, 132.8, 132.1, 130.3,
127.7, 126.9, 126.8, 120.9, 107.1, 76.4, 22.5. UV-vis: λmax (log
ꢀ, THF) 417.0 (5.66), 548.0 (4.70) nm. HRMS (FAB): calcd for
C41H28N4O3Zn 688.1453, found 688.1480.
Oxid a tion of 19 to 20 by DDQ. In a 25 mL round-
bottomed flask hydroquinone 19 (58 mg, 0.084 mmol) in THF
(10 mL) was treated with DDQ (28 mg, 0.125 mmol) under
nitrogen for 5 min at room temperature. The solvent was
evaporated, and the product was purified by flash column
chromatography using 10-20% THF-hexanes as the eluant
to provide quinone 20 (49 mg, 85%) as a red solid (data given
above).
5,15-Dip h en yl-10-(2-isop r op oxy-4-m et h yl-3,6-b en zo-
qu in on e)p or p h yr in (Zn ) (21). Isopropenylmagnesium bro-
mide (0.45 mL, 0.225 mmol, 0.5 M in THF) was added slowly
to a solution of 5-(2-isopropoxycyclobutene-3,4-dionyl)-10,20-
diphenylporphyrin(Zn) (7) (100 mg, 0.15 mmol) in THF (20 mL)
at -78 °C, then the reaction mixture was allowed to warm to
room temperature. After the solution was recooled to -78 °C,
a few drops of aqueous ammonium chloride were added. After
being warmed to room temperature, the mixture was parti-
tioned between dichloromethane-water and dried over sodium
sulfate, and the solvent was evaporated. The crude product
was dissolved in THF (10 mL) and treated with DDQ (51 mg,
0.225 mmol). After the solution was stirred at room temper-
ature for 5 min, the solvent was evaporated and the product
was purified by flash column chromatography (silica gel, 2.5
× 10 cm, 10-20% THF-hexanes) to provide 21 (91 mg, 86%)
as a red solid. TLC (silica gel, THF-hexanes (1:3)): Rf ) 0.45.
Mp > 250 °C (acetone-hexanes, diffusion). IR (KBr pellet,
cm-1): 1651 (w), 1588 (w). 1H NMR (CDCl3, 300 MHz): δ 10.20
(s, 1 H), 9.35 (d, J ) 4.5 Hz, 2 H), 9.11 (d, J ) 4.8 Hz, 2 H),
9.07 (d, J ) 4.5 Hz, 2 H), 9.01 (d, J ) 4.5 Hz, 2 H), 8.27-8.33
(m, 2 H), 8.17-8.23 (m, 2 H), 7.76-7.84 (m, 6 H), 6.91 (s, 1
H), 4.19 (hept, J ) 6.3 Hz, 1 H), 2.41 (s, 3 H), 0.50 (d, J ) 6.3
Hz, 6 H). 13C NMR (CDCl3, 75 MHz): δ 189.5, 185.1, 150.4,
150.1, 149.50, 149.0, 145.0, 142.7, 134.9, 134.6, 133.8, 133.0,
132.5, 131.9, 130.3, 127.6, 126.8, 126.7, 125.7, 120.8, 106.80,
76.3, 30.7, 22.9. UV-vis: λmax (log ꢀ, THF) 416.5 (5.66), 548.0
(4.76) nm. HRMS (FAB): calcd for C42H30N4O3Zn 702.1609,
found 702.1609.
P r od u ct 23. Purple solid (40 mg, 0.042 mmol, 28%). TLC
(silica gel, hexanes-acetone (3:1)): Rf ) 0.4). Mp > 250 °C
(methylene chloride-hexanes, diffusion). IR (KBr pellet, cm-1):
1672 (s), 1597 (s), 1557 (w). 1H NMR (CDCl3, 400 MHz): δ
9.14 (d, J ) 4.4 Hz, 4 H), 8.95 (d, J ) 4.4 Hz, 4 H), 8.42 (dd,
J ) 7.6, 1.2 Hz, 2 H), 8.32 (m, 2 H), 8.24 (dd, J ) 7.6, 1.2 Hz,
2 H), 8.12 (d, J ) 7.2 Hz, 2 H), 7.93 (dt, J ) 7.6, 1.6 Hz, 2 H),
7.88 (dt, J ) 7.6, 1.6 Hz, 2 H), 7.76 (m, 6 H), 4.69 (hept, J )
6.0 Hz, 2 H), 0.64 (d, J ) 6.0 Hz, 12 H). 13C NMR (CDCl3, 100
MHz): δ 186.9, 182.9, 158.9, 150.3, 149.0, 142.6, 134.4, 134.2,
133.7, 132.8, 132.2, 130.3, 127.5, 127.1, 126.7, 126.6, 126.4,
121.1, 109.6, 76.7, 22.7. UV-vis λmax (log ꢀ, ether) 419.0 (5.53),
554.0 (5.08) nm. MS(FAB): m/z 952. HRMS (FAB): calcd for
C
58H40N4O6Zn 952.2239, found: 952.2238.
P r od u ct 24. Purple solid (32 mg, 0.034 mmol, 23%). TLC
(silica gel, hexanes-acetone (3:1)): Rf ) 0.4. Mp > 250 °C
(hexanes-ether (20:3)). IR (KBr pellet, cm-1): 1672 (s), 1597
1
(s). H NMR (CDCl3, 400 MHz): δ 9.14 (d, J ) 4.8 Hz, 4 H),
8.94 (d, J ) 4.4 Hz, 4 H), 8.43 (dd, J ) 8.0, 1.2 Hz, 2 H), 8.24
(dd, J ) 7.2, 1.2 Hz, 2 H), 8.21 (dd, J ) 7.6, 1.6 Hz, 4 H), 7.92
(dt, J ) 7.6, 1.2 Hz, 2 H), 7.86 (dt, J ) 7.6, 1.2 Hz, 2 H), 7.76
(m, 6 H), 4.51 (hept, J ) 6.4 Hz, 2 H), 0.56 (d, J ) 6.4 Hz, 12
H). 13C NMR (CDCl3, 100 MHz): δ 186.9, 182.8, 158.9, 150.3,
149.0, 142.6, 134.5, 134.4, 133.9, 133.7, 132.8, 132.3, 130.3,
127.5, 127.1, 126.7, 126.5, 121.3, 109.5, 22.7. UV-vis: λmax (log
ꢀ, Et2O) 419.5 (5.45), 553.5 (5.00), 600.0 (4.60) nm. MS(FAB):
m/z 952. HRMS (FAB): calcd for M + H+ C58H41N4O6Zn
953.2318, found: M + H+ 953.2361. Anal. Calcd for C58H40N4O6-
Zn‚2OEt2: C, 71.89; H, 5.49; N, 5.08. Found: C, 71.71; H, 5.48;
N, 5.10. (Note: The x-ray structure also revealed that each
molecule bonded with two molecules of ether).
syn -5,15-Bis(2-isop r op oxyp h en a n th r oqu in on yl)-10,20-
d ip h en ylp or p h yr in (Zn ) (25) a n d a n ti-5,15-Bis(2-isop r o-
p oxyp h e n a n t h r oq u in on yl)-10,20-d ip h e n ylp or p h yr in -
(Zn ) (26). Following the general procedure, above, 5,15-bis(2-
isopr opoxycyclobu t en e-3,4-dion yl)-10,20-diph en ylpor -
phyrin(Zn) (9) (140 mg, 0.175 mmol) in THF (14 mL) and
1-naphthyllithium (1.1 mL, 0.43 M in THF, 2.7 equiv) at -78
°C afforded the adduct. This was refluxed in xylene for 30 min
followed by air oxidation to afford a mixture of compounds 25
and 26, which were separated by column chromatography
(flash column, silica gel, 2 × 8 cm, ether-methylene chloride
(1:50), 26 eluted before 25).
P r od u ct 25. Purple solid (46 mg, 0.044 mmol, 25%). TLC
(silica gel, ether-methylene chloride (1:10)): Rf ) 0.6. Mp >
250 °C (hexanes-methylene chloride, diffusion). IR (KBr
5,15-Dip h en yl-10-(2-isop r op oxy-4,5-d im eth yl-3,6-ben -
zoqu in on e) p or p h yr in (Zn ) (22). Following a procedure
similar to that for 21, starting from 7 (100 mg, 0.15 mmol)
and 1-methyl-1-propenylmagnesium bromide (0.5 M in THF,
0.45 mL, 0.225 mmol), 22 (94 mg, 87%) was obtained as a red
solid after purification (flash column, silica gel, 2.5 × 10 cm).
TLC (silica gel, hexanes-THF (3:1)): Rf ) 0.52. Mp >250 °C
(acetone-hexanes, diffusion). IR (KBr pellet, cm-1): 1656 (w),
1
pellet, cm-1): 1663 (s), 1648 (s), 1621 (m), 1664 (s). H NMR
(CDCl3, 400 MHz): δ 9.71 (d, J ) 8.8 Hz, 2 H), 9.20 (d, J )
4.8 Hz, 4 H), 8.96 (d, J ) 4.8 Hz, 4 H), 8.36 (d, J ) 8.4 Hz, 2
H), 8.32 (m, 2 H), 8.29 (d, J ) 8.4 Hz, 2 H), 8.13 (br d, J ) 7.2
Hz, 2 H), 8.03 (br d, J ) 8.0 Hz, 2 H), 7.88 (dt, J ) 7.2, 1.2 Hz,
2 H), 7.73 (m, 8 H), 4.59 (hept, J ) 6.0 Hz, 2 H), 0.70 (d, J )
6.4 Hz, 14 H). 13C NMR (CDCl3, 100 MHz): δ 187.7, 185.3,
159.8, 150.4, 149.2, 142.6, 136.5, 135.5, 134.8, 134.2, 132.9,
132.8, 130.8, 130.5, 130.3, 130.1, 129.0, 128.6, 127.9, 127.8,
127.5, 126.6, 126.4, 122.7, 121.2, 109.3, 76.4, 22.8. UV-vis:
1
1598 (w). H NMR (CDCl3, 300 MHz): δ 10.20 (s, 1 H), 9.35
(d, J ) 4.5 Hz, 2 H), 9.15 (d, J ) 4.8 Hz, 2 H), 9.06 (d, J ) 4.8
Hz, 2 H), 9.01 (d, J ) 4.8 Hz, 2 H), 8.26-8.37 (m, 2 H), 8.15-
8.24 (m, 2 H), 7.72-7.88 (m, 6 H), 4.26 (hept, J ) 6.0 Hz, 1
H), 2.42 (s, 3 H), 2.28 (s, 3 H), 0.54 (d, J ) 6.0 Hz, 6 H). 13C
NMR (CDCl3, 75 MHz): δ 189.6, 187.1, 150.3, 150.1, 149.6,
149.1, 143.0, 134.9, 134.6, 132.8, 132.5, 131.8, 130.3, 127.5,
126.7, 120.6, 106.8, 76.0, 31.9, 25.1, 22.9. UV-vis: λmax (log ꢀ,
THF) 416.5 (5.74), 548.0 (4.71) nm. HRMS (FAB): calcd for
λmax (log ꢀ, Et2O) 419.0 (5.38), 550.0 (4.95) nm. MS(FAB): m/z
1052 (74). HRMS (FAB): calcd for C66H44N4O6Zn 1052.2552,
found 1052.2546.
P r od u ct 26. Purple solid (63 mg, 0.060 mmol, 34%). TLC
(silica gel, ether-methylene chloride (1:10)): Rf ) 0.7. Chro-
matographic purification (flash column, silica gel, 2 × 8 cm,
ether-methylene chloride (2:25)). Mp > 250 °C (methylene
chloride-hexanes, diffusion). IR (KBr pellet, cm-1): 1663 (s),
1603 (s). 1H NMR (DMSO-d6, 400 MHz): δ 9.57 (d, J ) 8.4
Hz, 2 H), 9.38 (d, J ) 4.4 Hz, 4 H), 8.73 (d, J ) 4.8 Hz, 4 H),
8.51 (d, J ) 8.4 Hz, 2 H), 8.26-8.18 (m, 8 H), 7.97 (dt, J ) 7.2
Hz, 2 H), 7.86 (dt, J ) 7.2 Hz, 2 H), 7.80 (m, 6 H), 4.74 (hept,
J ) 6.0 Hz, 2 H), 0.67 (d, J ) 6.0 Hz, 12 H). 13C NMR (CDCl3,
100 MHz): δ 187.7, 185.2, 159.7, 150.3, 149.2, 142.6, 136.5,
135.5, 134.5, 132.9, 132.7, 130.4, 130.3, 130.0, 128.9, 128.6,
127.9, 127.8, 127.5, 126.5, 122.7, 121.3, 109.2, 76.5, 29.7, 22.7.
UV-vis: λmax (log ꢀ, Et2O) 420.0 (5.59), 553.0 (5.14), 593.0
(4.66) nm. HRMS (FAB): calcd for C66H44N4O6Zn 1052.2551,
found 1052.2546.
C
43H32N4O3Zn 716.1766, found 716.1794.
syn -5,15-Bis(2-isop r op oxyn a p h t h oq u in on yl)-10,20-
d ip h en ylp or p h yr in (Zn ) (23) a n d a n ti-5,15-Bis(2-isop r o-
poxyn aph th oqu in on yl)-10,20-diph en ylpor ph yr in (Zn ) (24).
Following the general procedure, above, 5,15-bis(2-isopropoxy-
cyclobutene-3,4-dionyl)-10,20-diphenylporphyrin(Zn) (9) (120
mg, 0.149 mmol) in THF (7 mL) and phenyllithium in hexanes
(1.8 mL, 0.21 M, 0.447 mmol, 3 equiv) at -78 °C gave the 1,2-
adduct. This was refluxed in xylene for 30 min followed by air
oxidation to afford a mixture of compounds 23 and 24, which
were separated by column chromatography (flash column,
silica gel, 2.5 × 10 cm, hexanes-ether (20:3) gradient, com-
pound 23 was eluted after compound 24).

3-Cyclobutenyl-1,2-dione-Substituted Porphyrins
J . Org. Chem., Vol. 65, No. 6, 2000 1663
Oth er Tr a n sfor m a tion s of P or p h yr in -Qu in on e Dy-
a d s. 5-(2-Isop r op oxycyclobu ten e-3,4-d ion yl)-15-br om o-
10,20-d ip h en ylp or p h yr in (27). 5-(2-Isopropoxycyclobutene-
3,4-dionyl)-10,20-diphenylporphyrin (6) (120 mg, 0.200 mmol)
and NBS (48 mg, 0.27 mmol) in methylene chloride (50 mL)
in a 100 mL round-bottomed flask were stirred at room temp-
erature for 5 h. After removal of the solvent, the crude product
was isolated by flash column chromatography (flash column,
silica gel, 3.5 × 10 cm, hexanes-methylene chloride (1:3)) to
give a dark green solid (114 mg, 0.168 mmol, 84%). TLC (silica
gel, hexanes-methylene chloride (1:3)): Rf ) 0.35). Mp > 250
°C(methylene chloride-hexanes, diffusion). IR (KBr pellet,
4 H), 8.10 (d, J ) 8.4 Hz, 2 H), 7.84-7.78 (m, 6 H), 7.34 (d, J
) 8.8 Hz, 2 H), 5.92 (hept, J ) 6.4 Hz, 1 H), 4.08 (s, 3 H), 1.59
(d, J ) 6.0 Hz, 6 H). UV-vis: λmax (log ꢀ, CH2Cl2) 438.0 (5.38),
564.0 (4.08), 617.0 (4.20) nm. MS(FAB): m/z 768. HRMS
(FAB): calcd for C46H32N4O4Zn 768.1714, found 768.1683.
5-(4-Meth oxyp h en yl)-10,20-d ip h en ylp or p h yr in (30). A
mixture of 5-bromo-10,20-diphenylporphyrin (2) (195 mg, 0.360
mmol, 1.00), 4-methoxyphenylboronic acid (109 mg, 0.717
mmol, 1.99 equiv), potassium carbonate (397 mg, 2.877 mmol,
7.99 equiv), Pd(PPh3)4 (62 mg, 0.054 mmol, 0.15 equiv), and
toluene (25 mL) was heated at 90 °C for 20 h under nitrogen.
After removal of the potassium carbonate and solvent, the
residue was purified by chromatography (flash, silica gel, 2 ×
12 cm, hexanes-methylene chloride (2:1)) to give the product
as a red solid (169 mg, 0.297 mmol, 82%). TLC (silica gel,
hexanes-acetone (3:1)): Rf ) 0.5. Mp > 240 °C (methylene
chloride-hexanes, diffusion). IR (KBr pellet, cm-1): 3311 (m).
1H NMR (CDCl3, 400 MHz): δ 10.21 (s, 1 H), 9.33 (d, J ) 4.4
Hz, 2 H), 9.02 (d, J ) 4.8 Hz, 2 H), 8.91 (s, 4 H), 8.25 (d, J )
7.6 Hz, 4 H), 8.13 (d, J ) 8.4 Hz, 2 H), 7.80-7.78 (m, 6 H),
7.28 (d, J ) 8.4 Hz, 2 H), 4.10 (s, 3 H), -2.99 (s, 2 H). 13C
NMR (CDCl3, 100 MHz): δ 159.3, 141.8, 135.5, 134.9, 134.7,
131.5 (4C-N(br)), 127.7, 126.8, 120.5, 119.6, 112.0, 104.6, 55.5.
UV-vis: λmax (log ꢀ, THF) 411 (5.39), 506.8 (4.11), 541.4 (3.70),
581.6 (3.63) nm. HRMS (FAB): calcd for M + Li+ C39H28N4-
OLi: 575.2423, found 575.2449. Anal. Calcd for C39H28N4O:
C, 82.37; H, 4.96; N, 9.85. Found: C, 82.37; H, 5.02; N, 9.87.
5-Br om o-15-(4-m eth oxyp h en yl)-10,20-d ip h en ylp or p h y-
r in (31). A mixture of 5-(4-methoxyphenyl)-10,20-diphenylpor-
phyrin (30) (20 mg, 0.035 mmol, 1.00 equiv) and NBS (6 mg,
0.035 mmol, 1.00 equiv) in CH2Cl2 (5 mL) was stirred at room
temperature for 3 h. After removal of the solvent, the residue
was triturated once with boiling methanol (30 mL). The
resulting purple solid (22 mg, 0.034 mmol, 97%) was pure by
NMR and was not further purified. TLC (silica gel, hexanes-
acetone (2:1)): Rf ) 0.6. Mp > 250 °C. IR (KBr pellet, cm-1):
1
cm-1): 3318 (w),1785 (s), 1754 (s), 1581 (s). H NMR (CDCl3,
400 MHz): δ 9.61 (d, J ) 5.2 Hz, 2 H), 9.11 (d, J ) 4.8 Hz, 2
H), 8.87 (d, J ) 4.8 Hz, 2 H), 8.81 (d, J ) 4.8 Hz, 2 H), 8.17
(dt, J ) 6.4, 1.6 Hz, 4 H), 7.84-7.75 (m, 6 H), 5.88 (hept, J )
6.0 Hz, 1 H), 1.59 (d, J ) 6.0 Hz, 6 H), -2.39 (s, 2 H). UV-vis:
λ
max (log ꢀ, CH2Cl2) 429 (5.48), 526 (4.22), 567 (4.42), 606 (3.95),
665 (4.16) nm. MS(FAB): m/z 679. HRMS (FAB): calcd for M
+ Li+ C39H27N4O3BrLi 685.1427, found: 685.1413.
5-(2-Isopr opoxycyclobu ten e-3,4-d ion yl)-15-(4-m eth oxy-
p h en yl)-10,20-d ip h en ylp or p h yr in (28) fr om Su zu k i Cou -
p lin g of 27 w ith p-An isylbor on ic Acid . A mixture of 5-(2-
isopr opoxycyclobu t en e-3,4-dion yl)-15-br om o-10,20-di-
phenylporphyrin (27) (17 mg, 0.025 mmol), 4-methoxyphenylbor-
onic acid (8 mg, 0.05 mmol), Pd(Ph3P)4 (4 mg, 0.0038 mmol),
and potassium carbonate (28 mg, 0.20 mmol) in toluene (10
mL) was heated at 90 °C for 20 h under nitrogen. The product
was purified by filtration through a plug of silica gel (2 × 2
cm) under vacuum (hexane-methylene chloride (1:1)). The
product 27 was obtained as a dark green solid (11 mg, 62%).
TLC (silica gel, hexanes-acetone (3:2)): Rf ) 0.34). Mp > 240
°C (methylene chloride-hexanes, diffusion). IR (KBr pellet,
1
cm-1): 3315 (w),1785 (s), 1752 (s), 1575 (s). H NMR (CDCl3,
400 MHz): δ 9.16 (d, J ) 4.8 Hz, 2 H), 8.92 (d, J ) 4.8 Hz, 2
H), 8.83 (d, J ) 4.8 Hz, 2 H), 8.76 (d, J ) 4.8 Hz, 2 H), 8.19
(dt, J ) 6.0, 1.2 Hz, 4 H), 8.10 (d, J ) 8.4 Hz, 2 H), 7.81-7.75
(m, 6 H), 7.29 (d, J ) 8.8 Hz, 2 H), 5.89 (hept, J ) 6.4 Hz, 1
H), 4.09 (s, 3 H), 1.60 (d, J ) 6.4 Hz, 6 H), -2.35 (s, 2 H).
UV-vis: λmax (log ꢀ, CH2Cl2) 431 (5.58), 525 (4.12), 568 (4.36),
598 (3.81), 660 (4.01) nm. MS(FAB): m/z 713 (100). Anal. Calcd
for C46H34N4O4: C, 78.17; H, 4.85; N, 7.93. Found: C, 77.92;
H, 4.96; N, 7.66.
1
3319 (w). H NMR (CDCl3, 400 MHz): δ 9.66 (d, J ) 5.2 Hz,
2 H), 8.91 (d, J ) 4.8 Hz, 2 H), 8.83 (d, J ) 6.8 Hz, 2 H), 8.79
(d, J ) 6.0 Hz, 2 H), 8.19 (dd, J ) 9.6, 1.6 Hz, 2 H), 8.18 (d, J
) 10.4 Hz, 2 H), 8.12 (d, J ) 11.1 Hz, 2 H), 7.81 (m, 6 H), 7.27
(d, J ) 8.8 Hz, 2 H), 4.08 (s, 3 H), -2.73 (s, 2 H). 13C NMR
(CDCl3, 100 MHz): δ 159.5, 141.8, 135.5, 134.5, 134.2, 127.8,
126.7, 120.9, 120.7, 112.2, 102.7, 55.6 (the signals from C-N
were not observed due to exchange of the N-H proton). UV-
vis λmax (log ꢀ, THF) 419.0 (5.55), 516.8 (4.17), 552.2 (3.95),
595.6 (3.64), 652.6 (3.61) nm. MS(FAB): m/z 648. HRMS
(FAB): calcd for C39H27N4OBr 646.1368, found 646.1356.
5-(2-Isop r op oxyn a p h th oqu in on yl)-15-(4-m eth oxyp h e-
n yl)-10,20-d ip h en ylp or p h yr in (Zn ) (32). The reaction was
carried out following procedures similar to those for previous
quinone porphyrins. 5-(2-Isopropoxycyclobutene-3,4-dionyl-10,-
20-diphenylporphyrin(Zn) (29) (38 mg, 0.049 mmol, 1.00 equiv)
was treated with phenyllithium (0.4 mL, 0.23 M in THF, 0.09
mmol) to form the 1,2-adduct. The adduct was refluxed in
xylene and then allowed to oxidize open to the air to give
product 32 (24 mg, 0.028 mmol, 57%) as a purple solid after
chromatography (flash column, silica gel, 1.5 × 12 cm, hex-
anes-acetone (3:1) followed by flash column, silica gel, 1.5 ×
12 cm, hexanes-ether (4:1)). TLC (silica gel, hexanes-acetone
(1:2)): Rf ) 0.5. Mp > 250 °C (methylene chloride-hexanes,
5-(2-Isopropoxycyclobutene-3,4-dionyl)-15-(4-methoxyphenyl)-
10,20-diphenylporphyrin (28) is better prepared by the Stille
coupling of 31 (described below) with 10.
5-(2-Isopr opoxycyclobu ten e-3,4-d ion yl)-15-(4-m eth oxy-
p h en yl)-10,20-d ip h en ylp or p h yr in (28) fr om Stille Cou -
p lin g of 31 a n d 10. 5-Bromo-15-(4-methoxyphenyl)-10,20-
diphenylporphyin (31) (90 mg, 0.15 mmol; see below), compound
10 (125 mg, 0.29 mmol), Pd2(dba)3 (7 mg, 0.0075 mmol), and
triphenylarsine (13.8 mg, 0.045 mmol) in THF (10 mL) were
heated at 55 °C for 21 h under nitrogen. After removal of the
solvent the residue was taken up in methylene chloride and
ethyl acetate (1:2). Saturated aqueous KF solution was added,
and the mixture was stirred at room temperature for 30 min.
The organic layer was separated, dried, concentrated, and pur-
ified by filtration through a plug of silica gel (4.2 × 2 cm) under
vacuum (hexanes-methylene chloride (1:1)). The product was
obtained as a dark green solid (95 mg, 0.134 mmol, 88%).
5-(2-Isopr opoxycyclobu ten edion yl)-15-(4-m eth oxyph en -
yl)-10,20-d ip h en ylp or p h yr in (Zn ) (29). A mixture of 5-(2-
isopropoxycyclobutenedionyl)-15-(4-methoxyphenyl)-10,20-diphe-
nylporphyrin (28) (64 mg, 0.091 mmol, 1.00 equiv) in methylene
chloride (50 mL) and zinc acetate (50 mg, 0.273 mmol, 3.00
equiv) in methanol (20 mL) was stirred at room temperature
for 2.5 h. The mixture was poured into water, and the organic
phase was separated and washed three times with water. After
removal of the solvent, a dark green solid was obtained (70
mg, 0.091 mmol, 100%). Mp > 250 °C (at 210 °C the crystals
shrunk and changed color from dark green to purple) (meth-
ylene chloride-hexanes, diffusion). IR (KBr pellet, cm-1): 1782
1
diffusion). IR (KBr pellet, cm-1): 1671 (s), 1597 (s). H NMR
(CDCl3, 400 MHz): δ 9.13 (d, J ) 4.8 Hz, 2 H), 8.98 (d, J )
4.8 Hz, 2 H), 8.96 (d, J ) 4.8 Hz, 2 H), 8.93 (d, J ) 4.4 Hz, 2
H), 8.40 (dd, J ) 7.6, 1.6 Hz, 1 H), 8.30-8.25 (m, 3 H), 8.19-
9.16 (m, 3 H), 8.05 (dd, J ) 8.0, 2.4 Hz, 1 H), 7.89 (m, J ) 7.6,
1.6 Hz, 2 H), 7.79-7.71 (m, 6 H), 7.22 (d, J ) 8.4 Hz, 2 H),
4.52 (hept, J ) 6.4 Hz, 1 H), 4.04 (s, 3 H), 0.56 (d, J ) 6.0 Hz,
6 H). 13C NMR (CDCl3, 100 MHz): δ 187.0, 182.8, 159.2, 158.9,
150.4, 150.3, 150.1, 149.3, 142.7, 135.4, 135.3, 135.1, 134.6,
134.4, 134.3, 134.2, 133.7, 132.3, 132.2, 131.8, 130.2, 127.5,
127.1, 126.7, 126.6, 126.5, 121.9, 121.1, 112.1, 111.9, 108.4,
76.5, 55.5, 22.6. UV-vis: λmax (log ꢀ, Et2O) 402 (4.56), 421
(5.57), 455 (4.14), 554 (4.18), 592 (3.74) nm. MS(FAB): m/z
844. HRMS (FAB): calcd for C52H36N4O4Zn 844.2027, found
844.2068.
1
(s), 1751 (s), 1571 (s). H NMR (acetone-d6, 400 MHz): δ 9.44
(d, J ) 4.8 Hz, 2 H), 8.90 (d, J ) 4.8 Hz, 2 H), 8.87 (d, J ) 4.8
Hz, 2 H), 8.80 (d, J ) 4.8 Hz, 2 H), 8.22 (dt, J ) 6.0, 1.6 Hz,

1664 J . Org. Chem., Vol. 65, No. 6, 2000
Shi et al.
5-Vin yl-10,20-diph en ylpor ph yr in (33). A mixture of 5-bro-
mo-10,20-diphenylporphyrin (81 mg, 0.15 mmol), vinyltri-n-
butyltin (64 mg, 0.2 mmol), Pd2(dba)3 (7 mg, 0.0075 mmol),
triphenylarsine (18 mg, 0.06 mmol), and THF (10 mL) in a 25
mL round-bottomed flask was heated at 50 °C for 2.5 h, and
then the solvent was removed. The product was purified
through a plug of silica gel (SiO2, 2 × 2.5 cm, hexanes-
methylene chloride (2:1)) to give a purple solid (65 mg, 0.133
mmol, 89%). TLC (silica gel, hexanes-methylene chloride (1:
1)): Rf ) 0.26. Mp > 250 °C (methylene chloride-hexanes,
diffusion). IR (KBr, cm-1): 3309 (w). 1H NMR (CDCl3, 400
MHz): δ 10.16 (s, 1 H), 9.55 (d, J ) 4.8 Hz, 2 H), 9.30 (d, J )
4.4 Hz, 2 H), 9.29 (dd, J ) 17.2, 10.8 Hz, 1 H), 8.99 (d, J ) 4.8
Hz, 2 H), 8.97 (d, J ) 4.8 Hz, 2 H), 8.26-8.23 (m, 4 H), 7.82-
7.77 (m, 6 H), 6.56 (dd, J ) 11.2, 2.0 Hz, 1 H), 6.12 (dd, J )
17.2, 1.6 Hz, 1 H), -2.96 (s, 2 H). UV-vis: λmax (log ꢀ, Et2O)
407 (5.44), 509 (4.33), 542 (3.89), 587 (3.77), 644 (3.38) nm.
Anal. Calcd for C34H24N4: C, 83.58; H, 4.95; N, 11.47. Found:
C, 83.51; H, 4.92; N, 11.51.
5,15-Divin yl-10,20-d ip h en ylp or p h yr in (34). A mixture
of 5,15-dibromo-10,20-diphenylporphyrin (150 mg, 0.24 mmol,
1.0 equiv), vinyltri-n-butyltin (603 mg, 0.6 mmol, 2.50 equiv),
Pd2(dba)3 (11 mg, 0.012 mmol, 0.05 equiv), triphenylarsine
(14.7 mg, 0.048 mmol, 0.20 equiv), and THF (20 mL) was
stirred at 50 °C for 3 h. After workup and purification (flash
column, silica gel, 3 × 12 cm, hexanes-methylene chloride (2:
1)) a purple solid was obtained (112 mg, 0.217 mmol, 90%).
TLC (silica gel, hexanes-methylene chloride (1:1)): Rf ) 0.5.
Mp > 250 °C (methylene chloride-hexanes, diffusion). IR (KBr
pellet, cm-1): 3317 (w). 1H NMR (CDCl3, 400 MHz): δ 9.45
(d, J ) 6.4 Hz, 4 H), 9.19 (dd, J ) 23.2, 14.8 Hz, 2 H), 8.86 (d,
J ) 6.4 Hz, 4 H), 8.22-8.19 (m, 4 H), 7.81-7.75 (m, 6H), 6.52
(dd, J ) 14.8, 2.4 Hz, 2 H), 6.10 (dd, J ) 22.8, 2.0 Hz, 2 H),
-2.60 (s, 2 H). UV-vis: λmax (log ꢀ, THF) 416.8 (5.38), 515.8
(4.04), 556.0 (3.82), 596.2 (3.50), 656.8 (3.38) nm. MS(FAB):
m/z 521. HRMS (FAB): calcd for M + Li+ C36H26N4Li 521.2318,
found: 521.2308. Anal. Calcd for C36H26N4: C, 84.02; H, 5.09;
N, 10.89. Found: C, 83.84; H, 5.19; N, 10.79.
J ) 6.3 Hz, 1 H), 1.62 (d, J ) 6.0 Hz, 6 H), -2.64 (s, 2 H).
UV-vis: λmax (log ꢀ, CH2Cl2) 440.5 (5.04), 514.0 (3.95), 573.5
(4.11), 665.0 (3.76). MS(FAB): m/z 627. HRMS (FAB): calcd
for M + H+ C41H31N4O3 627.2396, found 627.2427. Anal. Calcd
for C41H30N4O3: C, 78.58; H, 4.83; N, 8.94. Found: C, 78.06;
H, 4.78; N, 8.84.
5-[(3-Isop r op oxycyclob u t en e-1,2-d ion yl)vin yl]-10,20-
d ip h en ylp or p h yr in (Zn ) (37). 5-[(3-Isopropoxy-1,2-dionyl)-
vinyl]-10,20-diphenylporphyrin (36) (64 mg, 0.102 mmol, 1.00
equiv) in methylene chloride (50 mL) and zinc acetate (36 mg,
0.196 mmol, 1.92 equiv) in methanol (20 mL) were stirred at
room temperature for 1.5 h in a 100 mL round-bottomed flask.
The mixture was then washed three times with water, and
solvent was removed to give a dark green solid (64 mg, 0.093
mmol, 91%). Both TLC and NMR indicated the presence of
pure compound, so no further purification was performed. Mp
> 250 °C (methylene chloride-hexanes, diffusion). IR (KBr
pellet, cm-1): 1774 (s), 1741 (s), 1574 (s). 1H NMR (DMSO-d6,
400 MHz): δ 10.56 (d, J ) 15.6 Hz, 1 H), 10.31 (s, 1 H), 9.60
(d, J ) 4.8 Hz, 2 H), 9.43 (d, J ) 4.4 Hz, 2 H), 8.92 (d, J ) 4.8
Hz, 2 H), 8.81 (d, J ) 4.4 Hz, 2 H), 8.21 (m, 4 H), 7.85 (m, 6
H), 7.30 (d, J ) 15.6 Hz, 1 H), 5.57 (hept, J ) 6.4 Hz, 1 H),
1.58 (d, J ) 6.4 Hz, 6 H). 13C NMR (DMSO-d6, 100 MHz): δ
193.4, 192.6, 191.8, 171.1, 149.9, 149.3, 148.9, 148.6, 143.1,
142.3, 134.3, 132.7, 132.6, 131.8, 129.1, 127.7, 126.8, 125.9,
121.3, 113.2, 108.4, 79.7, 22.5. UV-vis: λmax (log ꢀ, THF) 431.0
(5.14), 455.5 (5.23), 562.5 (4.04), 629.0 (4.36) nm. MS(FAB):
m/z 688.2. HRMS (FAB): calcd for C31H285N4O3 688.1453,
found 688.1476.
5-[(2-Isop r op oxyn a p h th a qu in on yl)vin yl]-10,20-d ip h e-
n ylp or p h yr in (Zn ) (38). 5-[(3-Isopropoxy-1,2-dionyl)vinyl]-
10,20-diphenylporphyrin(Zn) (37) (35 mg, 0.050 mmol, 1.00
equiv) in THF (8 mL) at -78 °C under nitrogen was treated
dropwise with 1 equiv of phenyllithium (0.27 M in THF, 0.2
mL). Immediate monitoring of the reaction mixture by TLC
showed disappearance of starting material. The reaction was
quenched with aqueous ammonium chloride at the same
temperature and then allowed to warm to room temperature.
After aqueous workup, the crude product was dissolved in
xylene, refluxed for 3 h, and then stirred at room temperature
under air. The crude product was purified by column chroma-
tography (flash column, silica gel, 1.5 × 6 cm, hexanes-acetone
(10:1)), giving a brown solid (18 mg, 0.023 mmol, 46%). Mp >
250 °C (methylene chloride-hexanes, diffusion). IR (KBr
5-Br om ovin yl-10,20-d ip h en ylp or h yr in (35). 5-Vinyl-
diphenylporphyrin (220 mg, 0.45 mmol, 1.00 equiv) in ethanol-
free chloroform (130 mL) was treated with pyridinium tribro-
mide (199 mg, 0.55 mmol, 1.23 equiv) as a purple solid, and
the mixture was stirred overnight. The reaction mixture was
washed twice with water and then purified by filtration
through a plug of silica gel to give a purple solid (110 mg, 0.20
mmol, 44%). An analytical sample was prepared by purifica-
tion through flash column chromatography (flash column,
silica gel, 3 × 9 cm, hexanes-methylene chloride (3:1)) and
crystallization. TLC (silica gel, hexanes-methylene chloride
(1:1)): Rf ) 0.5. Mp > 250 °C (methylene chloride-hexanes,
1
pellet, cm-1): 1660 (s), 1595 (s). H NMR (CDCl3, 400 MHz):
δ 10.48 (d, J ) 16.0 Hz, 1 H), 10.09 (s, 1 H), 9.64 (d, J ) 4.8
Hz, 2 H), 9.27 (d, J ) 4.4 Hz, 2 H), 9.03 (d, J ) 4.8 Hz, 2 H),
8.99 (d, J ) 4.4 Hz, 2 H), 8.23 (m, 4 H), 7.89 (d, J ) 7.2 Hz, 1
H), 7.80 (m, 7 H), 7.55 (m, 2 H), 7.48 (d, J ) 16.4 Hz, 1 H),
5.28 (hept, J ) 5.6 Hz, 1 H), 1.48 (d, J ) 6.4 Hz, 6 H). 13C
NMR (CDCl3, 100 MHz): δ 150.1, 149.7, 149.3, 149.1, 142.6,
141.7, 134.5, 133.6, 133.1, 132.5, 132.3, 131.7, 130.3, 127.5,
126.6, 126.3, 125.7, 120.9, 77.2, 23.4. UV-vis: λmax (log ꢀ, THF)
420.5 (5.72), 554.5 (5.43), 633.5 (5.39) nm. MS(FAB): m/z 764.
1
diffusion). IR (KBr pellet, cm-1): 3308 (w). H NMR (CDCl3,
400 MHz): δ 10.19 (s, 1 H), 9.64 (d, J ) 14.2 Hz, 1 H), 9.46 (d,
J ) 5.1 Hz, 2 H), 9.31 (d, J ) 4.8 Hz, 2 H), 8.23 (m, 4 H), 7.80
(m, 6 H), 7.06 (d, J ) 13.8 Hz, 1 H), -2.99 (s, 2 H). UV-vis:
λmax (log ꢀ, THF) 414.0 (5.66), 511.0 (4.34), 545.5 (3.94), 588.0
(3.80), 645.0 (3.46) nm. MS(FAB): m/z 567 (21). HRMS
(FAB): calcd for M + H+ C34H24N4Br 567.1184, found 567.1165.
Anal. Calcd for C34H23N4Br: C, 71.96; H, 4.09; N, 9.88; Br,
14.08. Found: C, 71.66; H, 4.04; N, 9.84; Br, 14.35.
5-[(3-Isop r op oxycyclob u t en e-1,2-d ion yl)vin yl]-10,20-
d ip h en ylp or p h yr in (36). A mixture of 5-bromovinyl-10,20-
diphenylporphyrin (291 mg, 0.515 mmol, 1.00 equiv), Pd2(dba)3
(21.3 mg, 0.023 mmol, 0.04 equiv), triphenylarsine (31 mg,
0.099 mmol, 0.19 equiv), 10 (400 mg, 0.928 mmol, 1.80 equiv),
and THF (40 mL) was heated at 50 °C for 21 h under nitrogen.
After removal of the solvent, the residue was triturated with
hexanes and then purified by filtration through a plug of silica
(solvent: methylene chloride-hexanes-acetone (10:30:0.25))
to give a dark green solid (248 mg, 0.396 mmol, 77%). Mp 232-
235 °C (methylene chloride-hexanes, diffusion). IR (KBr
pellet, cm-1): 3468 (w), 3314 (w), 1778 (s), 1740 (s), 1575 (s).
1H NMR (CDCl3, 400 MHz): δ 10.58 (d, J ) 15.6 Hz, 1 H),
10.16 (s, 1 H), 9.55 (d, J ) 5.1 Hz, 2 H), 9.27 (d, J ) 4.5 Hz,
2 H), 8.98 (d, J ) 4.8 Hz, 2 H), 8.94 (d, J ) 4.8 Hz, 2 H), 8.22
(m, 4 H), 7.81 (m, 6 H), 7.33 (d, J ) 15.6 Hz, 1 H), 5.67 (hept,
HRMS (FAB): calcd for
764.1757.
C47H32N4O3Zn 764.1765, found
Ack n ow led gm en t. The National Cancer Institute,
DHHS, supported this investigation through Grant No.
CA40157. We are most appreciative of the careful and
thoughtful proofreading of this paper by Dr. Eric Nickel,
and we gratefully acknowledge the skilled assistance
of Bao Do and David Blakesley in carrying out the X-ray
crystallographic studies.
Su p p or tin g In for m a tion Ava ila ble: A complete descrip-
tion of the X-ray crystallographic determination of the struc-
tures of compounds 9 and 24 and photocopies of spectroscopic
data (IR, 1H, 13C NMR) for those compounds not characterized
by elemental analysis. This material is available free of charge
via the Internet at http://pubs.acs.og.
J O9912799