Facile peripheral functionalization of porphyrins by Pd-catalyzed [3+2] annulation with alkynes

Article abstract of DOI:10.1002/anie.200603580

(Chemical Equation Presented) Going round the outside: The palladium-catalyzed coupling of meso-bromoporphyrins with a variety of internal alkynes efficiently provides peripherally cyclopentadiene-fused porphyrins. This modification has a significant impa

Full text of DOI:10.1002/anie.200603580

Communications
Porphyrinoids
DOI: 10.1002/anie.200603580
Facile Peripheral Functionalization of Porphyrins
by Pd-Catalyzed [3+2] Annulation with
Alkynes**
Akhila K. Sahoo, Shigeki Mori, Hiroshi Shinokubo,*
and Atsuhiro Osuka*
The electronic nature of a porphyrin ring is susceptible to
modifications through the introduction of fused p-conjugated
segments at the periphery.[1] This feature has been employed
as a strategy for the creation of a variety of conjugated
porphyrin systems that exhibit unique optical and electro-
chemical properties and which are expected to have applica-
tions in various types of functional materials. However,the
introduction of such fused p systems on porphyrins often
requires laborious multistep synthesis and suffers from
frustratingly low yields. It is clear that novel and direct
transformations of porphyrins are needed for further devel-
opment of this area.[2]
A few transition-metal-catalyzed cross-coupling reactions,
such as the Sonogashira and Suzuki–Miyaura reactions,have
been successfully applied to porphyrins.[3] However,applica-
tion of modern transition-metal-catalyzed reactions to por-
phyrin synthesis is still limited. We envisaged that a carbon–
carbon bond-forming reaction of meso-bromoporphyrins with
alkynes by carbopalladation[4] would be useful in generating a
new molecular entity. We report herein an efficient way to
incorporate a fused cyclopentadiene moiety into porphyrins
such that the porphyrin p system is significantly perturbed.
The wide scope of this procedure offers us rapid access to a
diverse range of functionalized porphyrins. In addition,this
cross-annulative coupling reaction allows a modular approach
[5–7]
to a fascinating p system,namely,78, -dehydropurpurin.
A mixture of 5-bromo-10,20-bis(3,5-di-tert-butylphenyl)-
porphyrinnickel(II) (1; M = Ni) and diphenylacetylene
(1.2 equiv) in 1,4-dioxane was heated at reflux in the presence
of a catalytic amount of Pd(OAc)2/Ph3P and K2CO3. We found
[*] Dr. A. K. Sahoo, S. Mori, Prof. Dr. H. Shinokubo, Prof. Dr. A. Osuka
Department of Chemistry
Graduate School of Science
Kyoto University
PRESTO & CREST
Japan Science and Technology Agency (JST)
International Innovation Center (IIC)
Kyoto University
Sakyo-ku, Kyoto 606-8502 (Japan)
Fax: (+81)75-753-3970
E-mail: hshino@kuchem.kyoto-u.ac.jp
osuka@kuchem.kyoto-u.ac.jp
[**] This workwas partly supported by a Grant-in-Aid for Scientific
Research (no. 18685013) from MEXT. H.S. acknowledges the Asahi
Glass Foundation for financial support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Table 1: Pd-catalyzed [3+2] annulation of porphyrin with alkynes.[a]
that dehydropurpurin 2a (M = Ni,R = Ph) was formed in
10% yield along with the debrominated porphyrin
(Scheme 1). The parent mass ion peak of 2a (M = Ni) was
observed at m/z 918.4136 (calcd for [C62H60N4Ni]+ = 918.4166
Entry
R
M
Product
Yield (%)
1
2
3
4
5
6
7
8
Ph
Ni
Ni
Ni
Ni
Ni
Cu
Cu
Zn
Zn
Zn
2a (M=Ni)
2b (M=Ni)
2c (M=Ni)
2d (M=Ni)
2e (M=Ni)
2a (M=Cu)
2e (M=Cu)
2a (M=Zn)
2b (M=Zn)
2 f (M=Zn)
78
81
78
82
85
87
86
79
78
69
4-CF3(C6H4)
4-MeO(C6H4)
2-thienyl
nPr
Ph
nPr
Ph
9
4-CF3(C6H4)
4-MeO(C6H4)
10[b]
[a] Reaction conditions: [Pd2(dba)3] (1.5 mmmol), o-tol3P (6.0 mmmol),
meso-bromoporphyrin (30 mmmol), alkyne (45 mmmol), Cy2NMe
(0.15 mmol), toluene (1.5 mL), reflux, and 16–24 h. Ar=3,5-di-tert-
butylphenyl. [b] Ar=3,5-dioctyloxyphenyl.
Scheme 1. Pd-catalyzed [3+2] annulation of porphyrin with alkynes.
Cy =cyclohexyl, dba=trans,trans-dibenzylideneacetone, tol=tolyl.
[M]+) in its high-resolution electro-
spray-ionization
(HRESI-TOF)
time-of-flight
spectrum.
mass
1H NMR and H-H COSY spectra of
2a (M = Ni) showed the presence of
seven pyrrolic b protons: six doublets
and one singlet (d = 7.36 ppm)
appear,and the singlet can be
assigned as H1 (see the Supporting
Information). After extensive optimi-
zation,the catalyst system comprising
[Pd2(dba)3]/tris(o-tolyl)phosphine
and dicyclohexylmethylamine in tol-
uene delivered 2a (M = Ni) in 78%
yield. The reaction proceeded cleanly
without by-products,other than the
debrominated porphyrin,and none of
the simple addition product without
cyclization was detected in the reac-
tion mixture.
The annulation reaction with var-
ious alkynes is summarized in Table 1.
This process was found to have a wide
scope in regard to the metal ions at
the center of the porphyrin ring and
the alkynyl substituents. The reaction
provided the desired products in good
to excellent yields with aromatic and
aliphatic alkynes. Zinc and copper
porphyrins 1 (M = Zn and Cu) also
underwent this annulation reaction
with excellent yields.
Figure 1. X-ray structures of 2a (M=Ni and Cu) and 3·iPrOH. a) Top view and b) side view of 2a
(M=Ni), and c) top view of 2a (M=Cu); d) top view and e) side view of 3. The thermal ellipsoids are at
the 50% probability level. Hydrogen atoms and tert-butyl groups are omitted for clarity.
X-ray crystallographic analyses
unambiguously elucidated the struc-
tures of 2a (M = Ni or Cu),and
showed the presence of a fused five-
membered ring (Figure 1).[8] The porphyrin framework of the
nickel derivative is almost flat but slightly ruffled with small
deviations (< 0.2 Š) from the mean plane. Annulation with a
diphenylethene moiety results in contraction of the inner
cavity,which leads to a better fit of the small nickel(II) ion.
groups on the diphenylethene moiety is nearly perpendicular
(72.88) to the cyclopentadiene ring,but the other one is nearly
coplanar (32.08),which may permit its effective conjugation
À
with the porphyrinic p network. The C C double bond is
relatively long at 1.374 Š,which indicates that this bond
participates in the aromatic conjugated system. The copper
derivative exhibits a similar structure.
À
À
The Ni N1 bond (1.904 Š) is shorter than the other Ni N
bonds (1.942–2.002 Š). Interestingly,one of the phenyl
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Scheme 2 shows a plausible catalytic cycle. Oxidative
0
À
addition of Pd to the C Br bond of 1 triggers the formation
of porphyrinylpalladium A. Subsequent carbopalladation of
À
A at the C C triple bond provides alkenylpalladium species
Scheme 2. A plausible mechanism for the Pd-catalyzed [3+2]
anulation.
B,which is then converted into palladacycle C by intra-
À
molecular activation of the C H bond. Reductive elimination
eventually furnishes cyclized porphyrin 2 and regenerates the
Pd0 species. An intramolecular Heck-type reaction (carbo-
palladation–elimination sequence) of B is another possible
pathway,but this involves unfavorable anti- b-hydride elimi-
nation.
Figure 2. a) UV/Vis absorption spectra of 2a (M=Ni and Cu), and 2e
(M=Ni) in CHCl3. b) Change in the UV/Vis absorption spectra of 2a
(M=Zn) in CHCl3 under ambient conditions.
The UV/Vis absorption spectra of 2a (M = Ni and Cu)
and 2e (M = Ni; Figure 2a) exhibit substantially different
shapes from those of typical porphyrins. Split Soret bands
indicate the electronic structure has been significantly altered.
In fact,DFT calculations elucidate significant development of
frontier orbitals in the five-membered ring along with a much
smaller gap between the highest occupied molecular orbital
(HOMO) and the lowest unoccupied molecular orbital
(LUMO; see the Supporting Information). Cyclic voltamme-
try studies showed a small separation between the first
oxidation and the first reduction potential (DE = 1.66 V) for
2a (M = Ni) relative to that of 5,15-bis(3,5-di-tert-butylphe-
nyl)porphyrinnickel(II) (DE = 2.29 V). Incorporation of p or-
À
by oxidation of the outer C C double bond. The assignment
of 3 was based on HRESI-TOF mass and 13C NMR spectra,
the latter of which indicated the presence of two carbonyl
groups in 3. Final elucidation of the structure was accom-
plished by X-ray crystallographic analysis of crystals of 3
grown by vapor diffusion of isopropyl alcohol into a chloro-
form solution (Figure 1de).[9] The porphyrin framework of 3
is perfectly flat,without any distortion. The two benzoyl
groups are positioned close to each other and this accounts for
1
the temperature-dependent H NMR spectra of 3 (see the
Supporting Information). The strain induced by a bicyclo-
[3.3.0]octane skeleton would increase the reactivity of 2
toward oxidation. Contrasting photochemical stabilities of 2a
(M = Ni and Cu) suggested the involvement of singlet oxygen
in this conversion.
In conclusion,the palladium-catalyzed coupling reaction
of meso-bromoporphyrins with a variety of internal alkynes
efficiently provides peripherally cyclopentadiene-fused por-
phyrins by a rational one-step synthetic protocol. Incorpo-
À
bitals from the C C double bond resulted in a breaking of the
symmetry of the porphyrin p system and expansion of the
porphyrinic p network,as evident from the absorption
spectra,which differ significantly from the typical spectra of
porphyrins. Characteristically,the absorption spectra reach
into the near infrared region.
During the measurement of the absorption spectra we
encountered an interesting phenomenon with 2a (M = Zn).
The absorption spectrum of 2a (M = Zn) in CHCl3 was
completely different from that of the typical porphyrin-like
shape after exposure of the solution to air under room light
for 3 h (Figure 2b). This process was found to be quantitative
conversion of 2a (M = Zn) into meso,b-dibenzoylporphyrin 3
À
ration of the C C double bond alters both the electronic and
chemical properties of porphyrins. This efficient and direct
functionalization indicates the prospect of using transition-
metal-catalyzed reactions in porphyrin chemistry. Investiga-
tions on the application of this strategy to multiporphyrinic
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Chemie
compounds and elucidation of the mechanism of oxidative
cleavage of 2a (M = Zn) are currently in progress.
Received: September 1,2006
Published online: November 9,2006
Keywords: alkynes · fused-ring systems · oxidation · palladium ·
.
porphyrinoids
[1] a) M. G. H. Vicente,K. M. Smith, J. Porphyrins Phthalocyanines
2004, 8,26; b) H. S. Gill,M. Harmjanz,J. Santamaria,I. Finger,
M. J. Scott, Angew. Chem. 2004, 116,491; Angew. Chem. Int. Ed.
2004, 43,485; c) S. Richeter,C. Jeandon,J. P. Gisselbrecht,R.
Ruppert,H. J. Callot, J. Am. Chem. Soc. 2002, 124,6168; d) D. M.
Shen,C. Liu,Q. Y. Chen, Chem. Commun. 2005,4982; e) S. Fox,
R. W. Boyle, Chem. Commun. 2004,1322; f) K. Kurotobi,K. S.
Kim,S. B. Noh,D. Kim,A. Osuka, Angew. Chem. 2006, 118,4048;
Angew. Chem. Int. Ed. 2006, 45,3944; g) O. Yamane,K. Sugiura,
H. Miyasaka,K. Nakamura,T. Fujimoto,K. Nakamura,T.
Kaneda,Y. Sakata,M. Yamashita,
h) H. J. Callot,E. Schaeffer,R. Cromer,F. Metz,
Chem. Lett. 2004, 33,40;
Tetrahedron
1990, 46,5253; i) A. Tsuda,A. Osuka, Science 2001, 293,79.
[2] For a review on recent examples of novel transformations of
porphyrins,see: M. O. Senge,J. Richter, J. Porphyrins Phthalo-
cyanines 2004, 8,934.
[3] For reviews,see: a) W. M. Sharman,J. E. Van Lier, J. Porphyrins
Phthalocyanines 2000, 4,441; b) J. Setsune, J. Porphyrins Phtha-
locyanines 2004, 8,93.
[4] For annulation reactions with alkynes induced by carbopalladation,
see: a) G. Wu,A. Rheingold,S. J. Geib,R. F. Heck,
Organo-
metallics 1987, 6,1941; b) R. Grigg,P. Kennewell,A. Teasdale,V.
Sridharan, Tetrahedron Lett. 1993, 34,153; c) R. C. Larock,M. J.
Doty,Q. Tian,J. M. Zenner, J. Org. Chem. 1997, 62,7536.
[5] a) A. Nakano,N. Aratani,H. Furuta,A. Osuka, Chem. Commun.
2001,1920; b) C. Bauder,R. Ocampo,H. J. Callot, Tetrahedron
1992, 48,5135; c) H. Klement,M. Helfrich,U. Oster,S. Schoch,
W. Rüdiger, Eur. J. Biochem. 1999, 265,862.
[6] Purpurins are a class of porphyrins which have potential applica-
tion in artificial photosynthesis and photodynamic therapy.
[7] The synthesis of porphyrins with fused five-membered exocyclic
rings is also challenging and extensively studied. For leading
references,see: a) J. K. Laha,C. Muthiah M. Taniguchi,J. S.
Lindsey, J. Org. Chem. 2006, 71,7049; b) B. Zhang,T. D. Lash,
Tetrahedron Lett. 2003, 44,7253; c) K. M. Smith,K. C. Langry,
O. M. Minnetian, J. Org. Chem. 1984, 49,4602.
[8] Crystal data of 2a (M = Ni): C68H64Cl2N4Ni, Mr = 1066.84,mono-
clinic,space group Cc (no. 9), a = 35.997(12), b = 5.8843(15), c =
26.293(8) Š, b = 96.469(12)8, V= 5534(3) Š3, Z = 4, 1calcd
=
1.280 gcmÀ3
unique reflections, R = 0.0971, Rw = 0.2832 (all data),GOF
, T= 90(2) K,10185 measured reflections,7628
=
1.041 (I > 2.0s(I)). Crystal data of 2a (M = Cu): C68H64Cl2N4Cu,
Mr = 1071.67,monoclinic,space group Cc (no. 9), a = 35.996(13),
b = 5.847(2), c = 26.325(9) Š, b = 96.380(13)8, V= 5506(3) Š3,
Z = 4, 1calcd = 1.293 gcmÀ3, T= 123.1 K,11657 measured reflec-
tions,8262 unique reflections, R = 0.0774, Rw = 0.2285 (all data),
GOF = 1.056 (I > 2.0s(I)). CCDC-619420 (2a (M = Ni)),CCDC-
619421 (2a (M = Cu)),and CCDC-619419
( 3) contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[9] Crystal data of 3: C71H84O5N4Zn, Mr = 1138.85,triclinic,space
¯
group P1 (no. 2), a = 11.688(3), b = 15.783(4), c = 19.429(6) Š,
a = 112.513(10),
b = 95.172(11),
g = 104.909(8)8,
V=
3127.3(14) Š3, Z = 2, 1calcd = 1.209 gcmÀ3, T= 123(2) K,30667
measured reflections,14114 unique reflections, R = 0.0601, Rw =
0.1708 (all data),GOF = 1.033 (I > 2.0s(I)).
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