Spin-state control of thermal and photochemical Bergman cyclization

Article abstract of DOI:10.1039/c3cc34471a

Thermal Bergman cyclization of Pt(ii) dialkynylporphyrins reveals a marked reduction in the cyclization temperature relative to the free base and Zn(ii) derivatives. In contrast, photogenerated ³ππ* population produces no detectable Bergman photocyclization, suggesting that the photoreactivities of the related free base and Zn(ii) derivatives occurs via the ¹ππ* state.

Full text of DOI:10.1039/c3cc34471a

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Spin-state control of thermal and photochemical
Bergman cyclization†‡
Leigh J. K. Boerner,a Maren Pink,b Hyunsoo Park,b Amanda LeSueura and
Jeffrey M. Zaleski*a
Cite this: Chem. Commun., 2013,
49, 2145
Received 14th June 2012,
Accepted 26th January 2013
DOI: 10.1039/c3cc34471a
www.rsc.org/chemcomm
Thermal Bergman cyclization of Pt(II) dialkynylporphyrins reveals a singlet excitation leads to Bergman product while triplet-state
marked reduction in the cyclization temperature relative to the photosensitization produces mainly alkyne-reduced species.4
free base and Zn(II) derivatives. In contrast, photogenerated 3pp* Computational analyses of simple enediynes5 support these
population produces no detectable Bergman photocyclization, observations by demonstrating that while singlet excitation
suggesting that the photoreactivities of the related free base and leads to formation of the 1,4-diradical intermediate, triplet
Zn(II) derivatives occurs via the 1pp* state.
state population promotes out-of-plane distortions about the
double bond for simple enediynes, as well as in-plane distor-
Porphyrinoids have a rich electronic excited state history that has tions at the terminal carbon for aromatic enediyne systems.6
been exploited for Photodynamic Therapy (PDT).1 A limitation of These distortions are consistent with cis–trans isomerized
this technology is the diffusion-controlled requirement of the photoproducts7 and reduced alkyne species formed upon bimole-
diradical species, 3O2. Photoinduced triplet–triplet annihilation cular excited triplet state sensitization.
3
converts the pp* state of the porphyrinoid to ground state, with
The premise of this work is to determine if inserting the
concomitant generation of 1O2. Since solid tumors experience heavy atom Pt(II) into the porphryin core can unimolecularly
decreased oxygen levels, PDT as a treatment modality is not affect the Bergman cyclization of dialkynylporphyrins. Pt(II)
effective. However, radical-generating functionalities coupled to porphyrins are known to facilitate rapid intersystem crossing
the porphyrins have potential as advanced PDT agents for such and exhibit the 3pp* state.8 Base Pt(II) porphyrins exhibit
hypoxic environments as they maintain red spectral region photo- markedly quenched 1pp* lifetimes (r15 ps) and 3pp* long-
activation, while alleviating the need for external chemical cofactors. evities of >1 ms.9 Thus, understanding the specific state that
Photochemical Bergman cyclization of dialkynylporphyrins effectively produces the Bergman product will enhance H-atom
has paved the way for just such reagents if the outcome can be abstraction efficiency from potential biological substrates.
both controlled and optimized. Within this theme, our group
The synthesis of free base, Zn(II), and Ni(II) 2,3-ethynyl-
demonstrated that the free base and Zn(II) 2,3-diethynyl- 5,10,15,20-tetraphenylporphyrins were previously reported.2,10
5,10,15,20-tetraphenylporphyrins could be photocyclized and To insert Pt(II), 10 equiv. of Pt(acac)2 are complexed to dry
trapped using the meso-phenyl ring addition at visible wave- benzonitrile under N2 at 190 1C for 30 min (Scheme 1).
lengths in yields as high as 35%.2 Since for free base and Zn(II)
tetraphenylporphyrins, 1pp* excited-state lifetimes of 2–12 ns
3
and pp* state lifetimes of micro-to-milliseconds are the rule,3
it is unclear through which of the two excited states this
reaction occurs. Experimentally, Turro et al. demonstrated that
a Department of Chemistry, Indiana University, 800 East Kirkwood Avenue,
Bloomington, Indiana, USA. E-mail: zaleski@indiana.edu
Fax: +1 812-855-8300; Tel: +1 812-855-2134
b Molecular Structure Center, Indiana University, 800 East Kirkwood Avenue,
Bloomington, Indiana, USA
† This article is part of the ChemComm ‘Porphyrins and phthalocyanines’ web
themed issue.
‡ Electronic supplementary information (ESI): Details about X-ray structure data
collection for 1, 2, and 4. CCDC 882454–882456. For ESI and crystallographic data
Scheme 1 Synthesis of the Pt(II) series of porphyrins 1–3.
in CIF or other electronic format see DOI: 10.1039/c3cc34471a
c
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Chem. Commun., 2013, 49, 2145--2147 2145

Communication
ChemComm
The solution is cooled for 10 min, transferred into a solution of
2,3-dibromo-5,10-15-20-tetraphenylporphyrin in benzonitrile
and reacted at 190 1C for an additional 6.5 h. The crude product
is purified by activated neutral aluminum oxide column
chromatography to give (2,3-dibromo-5,10-15-20-tetraphenyl-
porphyrinato)platinum(II) (1) in 88% yield. Ethynyl units are
installed by treating 1 with three equivalents of trimethyl-
(trimethylstannylethynyl)silane, dry THF, and a Pd(0) catalyst
in an inert atmosphere and refluxed at 70–80 1C for 6 h. The
(2,3,-bis[trimethylsilylethynyl]-5,10,15,20-tetraphenylporphyrinato)-
platinum(II) (2) is isolated in 58% yield. Compound 2 is
deprotected at RT with 3 equivalents of a 1 M solution of
Scheme 2 Thermal Bergman cyclization of 3 leads to the cyclized 4 in 21–60%
yields, but photolysis results only in starting material.
tetrabutylammoniumfluoride (TBAF) in THF for 1.5
h to
afford (2,3-diethynyl-5,10,15,20-tetraphenylporphyrinato)platinum(II)
(3) in 40% yield.
Crystals suitable for X-ray analysis for three of the Pt(II) porphyrins
were obtained by slow evaporation of a 1 : 1 methanol–dichloro-
methane solution. Attempts to obtain the structure of (2,3-diethynyl-
5,10,15,20-tetraphenylporphyrinato) platinum(II) 3 were unsuccessful.
Instead, the Bergman product (10,15-diphenyl-piceno[20,1,2,3,4,5-
fghij]porphyrinato)platinum(II) 4 crystallized from this ambient
temperature solution after one week.
Fig. 1 Electronic absorption spectra of the Pt(II) porphyrins 1–4.
The thermal Bergman cyclization reactivity of 3 is intriguing.
Differential scanning calorimetry (DSC) of 3 shows an exothermic recovery of 96%. On the low temperature side, 3 cyclizes as
peak at 140 1C compared to 160 1C for the free-base and Zn(II) low as 60 1C over 4 h and gives the picenoporphyrin compound
derivatives.2 The reduced temperature and broadened nature of the in 34% yield, with 38% of the starting material recovered. The
peak indicate that the activation barrier for this Pt(II) dialkynyl- extended reaction time creates polymeric side products which
porphyrin is markedly lower than the free base and Zn(II) dialkynyl- are not separable and likely derive from oligomerization.
porphyrins. This same reactivity profile translates to solution
Representative electronic absorption spectra for the Pt(II)
(Table 1). Thermal cyclization studies of 3 show Bergman reactivity porphryins are shown in Fig. 1. The absorption spectra for the
at a lower solution temperature than any known H-terminated, alkynylated compounds 2 and 3 are bathochromatically shifted
porphyrinic-enediynes. For comparison, the free base derivative from the Pt(II)-dibromoporphyrin 1 due to the increased
cyclizes at 120 1C in 8 hours, resulting in the picenoporphyrin in delocalization of aromaticity caused by the additional triple
65% yield.2 The same reaction conditions for the Zn(II) derivative bonds. The electronic spectrum of the TMS-protected derivative
gives the cyclized compound in 70% yield. However, thermolysis of 3 2 is slightly more red-shifted than the deprotected product,
proceeds to completion at 115 1C after only 2 hours, producing with the B-band at l = 418 nm (e = 2.35 Â 105 MÀ1 cmÀ1) and
picenoporphyrin 4 in 45% yield, but with complete consumption of Q-bands at l = 524 and 564 nm (e = 2.28 Â 104 and e = 2.35 Â
starting material (Scheme 2). Higher yields are achieved at lower 104 MÀ1 cmÀ1, respectively). Similarly, the B-band of 3 lies at l =
temperature and shorter reaction times, but those reactions do not 414 nm (e = 2.26 Â 105 MÀ1 cmÀ1), with the Q-bands at 521 and
go to completion.
560 nm (e = 1.93 Â 104 and e = 1.73 Â 104 MÀ1 cmÀ1
,
Longer reaction times also result in a larger amount of side respectively), reflecting a comparable p-delocalization pathway.
product, regardless of reaction temperature (Table 1). The best
In contrast, benzannulation and meso-phenyl ring quench-
yields of the cyclized product result from a reaction time of 2 h ing of the diradical intermediate results in an extension of
at 95 1C, which produces 60% yield of the target compound p-delocalization, and a corresponding red-shift of the electronic
and 36% of remaining starting material, a total material spectrum. The B-band of 4 is now detected at l = 440 nm
(e = 1.16 Â 105 MÀ1 cmÀ1), and the two Q-bands lie at l = 603
and 611 nm (e = 3.28 Â 104 and e = 3.76 Â 104 MÀ1 cmÀ1
,
Table
1
Reaction conditions for the thermal Bergman cyclization of Pt(II)
respectively). It is known that addition of fused benzene rings
break the accidental degeneracy of the 1a1u and 1a2u HOMO
set. This relaxes the ideal forbidden/allowed characters of the
Q/B transitions causing the Q-bands to gain intensity at the
expense of the B-band.11
porphyrins
Alkyne terminus
Reaction conditions
STa (%)
Cycb (%)
H
H
H
H
H
TMS
TMS
Toluene, 60 1C, 4 h
Toluene, 80 1C, 1 h
Toluene, 95 1C, 1 h
Toluene, 95 1C, 2 h
Toluene, 115 1C, 2 h
Toluene, 190 1C, 24 h
Toluene, 150 1C, 24 h
38
50
50
36
—
64
92
34
40
47
60
45
—
—
Remarkably, 3 also undergoes spontaneous Bergman cyclization
on the benchtop at ambient temperature, which was revealed by the
X-ray structure of 4 from a 1 : 1 methanol–dichloromethane
solution. To probe whether the room temperature reaction was
a
b
Recovered starting compounds. Isolated yields of cyclized products. thermal, photoelectronic, or photothermal, three vials containing
c
2146 Chem. Commun., 2013, 49, 2145--2147
This journal is The Royal Society of Chemistry 2013

ChemComm
Communication
within the p-manifold. The kinetic evolution of these features are
synchronized and decay with t = 5.7 ms (l = 476 nm), which confirms
the identity of this long-lived state as 3pp* in origin as Pt(II)
porphyrins are known to be non-fluorescent and have 1pp* lifetimes
of r15 ps.9 Since the long-lived 3pp* is correlated with the absence
of photoelectronic reactivity of 3, the cyclization may be spin-state
regulated as the corresponding free base and Zn(II) dialkynyl-
porphyrins are both photochemically active and their base TPP
1
frameworks have 2–12 ns pp* lifetimes.3 Thus, despite the more
facile thermal reactivity of the Pt(II) analogue 3, 3pp* population
makes the photoelectronic cyclization pathway less viable. That no
triplet photoproduct is observed from this reaction may be system
and condition specific. The significant steric bulk in the vicinity of
the alkynes may help impede 3pp* state-preferred bond reduction.4,6
Additionally, the longer photolysis wavelength, and to a lesser extent
the diminished energy of the 3pp* state, may also preclude
significant formation of triplet-induced photoproducts observed
of high-energy photolysis of less conjugated enediynes.4
The thermal Bergman cyclization reactivity of Pt(II) dialkynyl-
porphyrins reveals a surprising reduction in the temperature at
which the picenoporphyrin product is formed relative to the free
base and Zn(II) derivatives. In contrast, photoexcitation leads to
no detectable photoelectronic Bergman cyclization. Transient
absorption confirms the kinetically competent photoexcited
state as 3pp* in nature, suggesting that this surface is less viable
for the photo-Bergman event, despite the facile ground-state
thermal reactivity. These results suggest that the photo-
reactivities of the free base and Zn(II) derivatives occur via the
1pp* state, thereby demonstrating spin-state selectivity of the
photo-Bergman reaction for these systems, and thus potential
utility in advanced PDT for hypoxic environments.
Fig. 2 Electronic absorption of the three samples of 3 and the cyclized 4 over
30 days, under N2, normalized to l = 415 nm. vial 1 was kept at RT on the benchtop,
vial 2 was kept at RT in the dark, and vial 3 was kept at À20 1C in the dark.
the same concentration of 3 in DCM were prepared. One vial was
left on the benchtop (light + RT), one vial was placed in a drawer
(dark + RT), and one shielded from light and placed in the freezer at
À20 1C (dark + cold). A vial of the same concentration of a control,
(2,3,-bis[trimethylsilylethynyl]-5,10,15,20-tetraphenylporphyrin-
ato)platinum(II) 2 was also left on the benchtop. The four
solutions were monitored by TLC and electronic absorption
spectroscopy for 30 days (Fig. 2). A green product indicative of
the cyclized 4 appears after 4 days from the light + RT vial, and
after 6 days from the dark + RT vial. Over 30 days, no 4 develops
in the dark + cold vial.
The electronic spectra for the bench-top cyclization experi-
ments show gradual growth at l = 600 and 613 nm, indicative of
the Pt(II) picenoporphyrin 4. For vial 1 (light + RT), these
transitions can be observed after 7 days, and continuously
increase throughout the 30-day period. In vial 2 (dark + RT),
the same features are evident after 7 days, although to a lesser
extent. The l = 613 nm band becomes prominent midway
through the 30-day evaluation and persists. In contrast, vial 3
shows no red-shifted absorption features, even after 30 days.
The photochemical contribution to this reaction in absence of
thermal energy was then evaluated by placing 5 mg of 3 in a quartz
Schlenk flask with 100 mL dry and degassed toluene, and irradiated
with a l Z 395 nm cutoff filter for 72 hours at 10 1C. No cyclized
product 4 is formed as 96% of the starting material is recovered.
Previous work by Nath et al.2 showed that the free base and Zn(II)
derivatives of the dialkynylporphyrin produce cyclized products in 15
and 35% yields, respectively, under these conditions. Photolytic
controls of the TMS derivative 2 and picenoporphyrin 4 result in
quantitative recovery of starting material. When the cooling bath was
removed during photolysis of 3, photothermal heating raised the
solution temperature to 30 1C over 72 h, and cyclized 4 was isolated
in 21%. Heating of 3 in the dark to 30 1C for 72 h also produces 4 in
comparable 12% yield, indicating that this is indeed a thermally-
induced reaction.
The generous support of the National Science Foundation (CHE-
0956447) is gratefully acknowledged. The authors thank Professor
Felix Castellano and Dr Fabian Spaenig of Bowling Green State
University for assistance with kinetics measurements.
Notes and references
¨
1 M. B. Bakar, M. Oelgemoller and M. O. Senge, Tetrahedron, 2009,
65, 7064; A. Juarranz, P. Jaen, F. Sanz-Rodriguez, J. Cuevas and
S. Gonzalez, Clin. Transl. Oncol., 2008, 10, 148.
2 M. Nath, M. Pink and J. M. Zaleski, J. Am. Chem. Soc., 2005, 127, 478.
3 S. Gentemann, N. Y. Nelson, L. Jaquinod, D. J. Nurco, S. H. Leung,
C. J. Medforth, K. M. Smith, J. Fajer and D. Holten, J. Phys. Chem. B,
1997, 101, 1247; J. Rodriguez, C. Kirmaier and D. Holten, J. Am.
Chem. Soc., 1989, 111, 6500.
4 A. Evenzahav and N. J. Turro, J. Am. Chem. Soc., 1998, 120, 1835.
5 H. Dong, B.-Z. Chen, M.-B. Huang and R. Lindh, J. Comput. Chem.,
2012, 33, 537.
6 A. E. Clark, E. R. Davidson and J. M. Zaleski, J. Am. Chem. Soc., 2001,
123, 2650.
7 P. J. Benites, R. C. Holmberg, D. S. Rawat, B. J. Kraft, L. J. Klein,
D. G. Peters, H. H. Thorp and J. M. Zaleski, J. Am. Chem. Soc., 2003,
125, 6434.
Consistent with this picture is the kinetic evolution of transient
absorption spectra of 3 following l = 476 nm excitation in degassed
benzonitrile (ESI‡). The spectral profile exhibits a classic excited-state
Soret absorption maximum at l = 471 nm, a weaker, tailing feature
beyond 600 nm, and ground-state bleaching at l = 530 nm and
565 nm. These are commensurate with Pt(II) tetraphenylporphyrin
transient absorption markers resulting from electron promotion
8 J. B. Callis, J. M. Knowles and M. Gouterman, J. Phys. Chem., 1973,
77, 154; D. Eastwood and M. Gouterman, J. Mol. Spectrosc., 1970, 35, 359.
9 D. Kim, D. Holten, M. Gouterman and J. W. Buchler, J. Am. Chem.
Soc., 1984, 106, 4015; G. Ponterini, N. Serpone, M. A. Bergkamp and
T. L. Netzel, J. Am. Chem. Soc., 1983, 105, 4639.
10 H. Aihara, L. Jaquinod, D. J. Nurco and K. M. Smith, Angew. Chem.,
Int. Ed., 2001, 40, 3439.
11 M. Gouterman, in The Porphyrins, ed. D. Dolphin, Academic Press,
New York, 1978, vol. 3.
c
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Chem. Commun., 2013, 49, 2145--2147 2147