Porphyrins: Syntheses and Properties

Abstract

It is well known that meso-tetraarylporphyrins are obtained readily by condensation reactions between pyrroles and aromatic aldehydes. The 2+2 type condensation of aryldipyrrylmethanes and the second aromatic aldehyde is useful for synthesizing porphyrins with mixed meso-aryl groups, and further transformations of the porphyrin periphery are performed conveniently by using organometallic methodology. Some meso-aryl substituted porphyrins are designed for supramolecular application and photosensitizing effect. Porphyrins substituted at pyrrole β-positions are obtainable by using Barton–Zard synthesis, and these compounds are further converted into benzoporphyrins that are structurally similar to phthalocyanines and play an important role in the development of a variety of photo-functional materials. Porphyrins more heavily π-extended than benzoporphyrin are focused in the last part of this chapter. Multiple porphyrin cores are directly bridged by π-units or aromatic substituents at the porphyrin periphery are forced to come into π-conjugation with the porphyrin π-system by Scholl reactions, leading to strong infrared absorption bands at longer wavelength beyond 1000 nm, very small HOMO–LUMO gap, and very high two-photon absorption efficiency.

1 Introduction

Porphyrins are fully π-conjugated macrocycles where four pyrrole rings are connected by sp²-hybridized carbon atoms. The macrocyclic π-conjugation and the dianionic tetradentate coordination site provide basis for a wide variety of applications. Photophysical, electrochemical, and coordination properties of porphyrins have been drawing great interest in a variety of scientific fields and these properties are tunable by the abundant methodology for structure modification. Comprehensive reviews on the current porphyrin studies have been published as multi-volume reference books (Kadish et al. 2000, 2010; Dolphin 1978). This chapter describes functionalized porphyrins with focusing on their synthetic methodology and their properties caused by structural diversity. Although some aspects of application to material science and medicine will be mentioned here, they are arbitrarily selected just for examples. A large number of porphyrin analogues (expanded, contracted, and isomeric porphyrins) have been developed these days and their unusual structure and properties have been adding great insights into the porphyrin chemistry. These subjects have recently been reviewed (Sessler et al. 2017), and not included here.

2 meso-Tetra-substituted Porphyrins

2.1 Condensation of Pyrrole and Aldehyde

meso-Tetraarylporphyrins are produced by simple procedures known as a Rothemund method and a Longo-Adler method (Rothemund 1935; Adler et al. 1967). After heating a mixture of pyrrole and aromatic aldehyde in acetic acid or propionic acid under aerobic conditions, the reaction mixture was left overnight at room temperature to generate crystalline A₄-type porphyrins with D_4h symmetry usually in the yields more or less 20%. Since rotation of meso-aryl groups with ortho-substituents is limited, conformational isomers called atropisomers are separated and their stability is dependent on the bulkiness of the ortho-substituents. Collman’s group constructed an O₂-binding heme model by using an αααα-isomer of meso-tetra(o-aminophenyl)porphyrin 2 that was obtained by condensation of pyrrole and ortho-nitrobenzaldehyde followed by SnCl₂ reduction (Collman et al. 1975). 2 is regarded as a scaffold for molecular architecture of unique stereochemistry (Fig. 3.1). Four possible atropisomers (αααα, ααββ, αααβ, αβαβ) occur at equilibrium in a 1:2:4:1 statistical ratio, but Lindsey found that the αααα isomer with all four amino groups on the same face of the porphyrin plane was obtained in 66% yield after heating the benzene solution of the equilibrium mixture in the presence of silica gel due to the preferential adsorption of the target isomer (Lindsey 1980). On the other hand, Nishino reported that the αβαβ atropisomer of meso-tetra(o-nitrophenyl)porphyrin 1 could be enriched in refluxing toluene (Nishino et al. 1992). Therefore, equilibration in toluene at reflux followed by reduction and chromatographic separation produced 52% yield of the pure αβαβ atropisomer of 2.

Fig. 3.1

Atropisomerism of meso-tetraarylporphyrins

Unsymmetrical bridges were introduced into the ααββ-isomer of meso-tetra(o-aminophenyl)porphyrin 2 to give a 1:1 mixture of meso-3 and chiral-3 in the studies on molecular recognition by Ogoshi, Kuroda, and coworkers (Fig. 3.2) (Kuroda et al. 1995). The chiral-3 was separated into a C₂-symmetric enantiomer pair by HPLC on a chiral phase and the binding constants of their Zn complexes toward amino acid esters were dependent on the chirality of the enantiomeric porphyrins with sevenfold difference.

Fig. 3.2

Chiral porphyrins derived from meso-tetraarylporphyrins

Sugiura, Sakata, and coworkers separated A₃B-type porphyrin 4 and A₂B₂-type porphyrin 5 in 12% and 3% yield, respectively, from a mixture of porphyrin products in the mixed condensation of pyrrole with two different aromatic aldehydes under Longo–Adler reaction conditions (Fig. 3.3) (Sugiura et al. 1999). The ester groups of 4 and 5 were converted into formyl groups and then subjected to the mixed condensation with pyrrole again to give the pentameric porphyrin 6 in 25% yield using Lindsey’s protocol for hindered porphyrins. That is, a one-flask two-step procedure of acid-catalyzed condensation at room temperature in highly diluted CH₂Cl₂ solution followed by DDQ oxidation of the porphyrinogen intermediate (7 in Fig. 3.4) (Lindsey et al. 1987). The pentamer 6 was utilized as a precursor to the dendritic molecular architecture composed of 21 porphyrin nuclei and 64 benzene units through the condensation with pyrrole under Lindsey conditions. The final product was obtained in 44% yield and its molecular image was actually observed by STM as a square shape of 65 Å along the sides that is consistent with the theory 65.7 Å.

Fig. 3.3

Synthesis of square-shaped porphyrin oligomers

Fig. 3.4

Direct synthesis of A₃B-type meso-tetraarylporphyrin and its application to diporphyrin

Mixed condensations are an easy way to functional porphyrins such as used for chirality sensors. Nakanishi and Berova had pointed out that the exciton coupling of two porphyrins in a skewed conformation gives a strong CD couplet at the Soret band region at ca. 400 nm and its sign is diagnostic of the absolute configuration of the optically active guests that was bound cooperatively to the two porphyrin units (Huang et al. 1998). Their molecular design of the diporphyrin chiral sensor was modified by Borhan and coworkers. The mixed condensation of pentafluorobenzaldehyde, 4-carbomethoxybenzaldehyde, and pyrrole in the molar ratio of 3:1:4 according to Lindsey’s protocol afforded 19% yield of A₃B-type porphyrin 8 after chromatographic separation of a mixture of porphyrin products with statistical distribution of meso-aryl substitution pattern (Fig. 3.4) (Li et al. 2008). 8 was converted to Zn porphyrin dimer 9Zn₂ which was used for chirality sensing of optically active guest molecules such as diamines, aminoalcohols, and dialcohols. meso-Pentafluorophenyl groups increased Lewis acidity of Zn(II) and the guest binding was dependent on the chain length of the linker. Binding of the asymmetric guest molecules to 9Zn₂ induces face-to-face orientation of two porphyrin rings with their electronic transition moments in a skewed orientation. Thus, chirality of the guest molecule is translated into the helicity of the host molecule.

2.2 Lindsey Synthesis Using Dipyrrylmethanes

The above-mentioned Lindsey protocol of acid-catalyzed condensation followed by oxidation is applicable to selective formation of trans-A₂B₂-type porphyrin 11 from aryldipyrrylmethanes 10 and the second aromatic aldehyde (Fig. 3.5) (Ravikanth et al. 1998). But it should be remembered that decomposition of 10 and a porphyrinogen intermediate to pyrrole and aromatic aldehyde is also acid-catalyzed to result in scrambling of the meso-aryl substitution pattern in the porphyrin products. Lindsey also reported an alternative route to 11 under milder reaction conditions taking advantage of more reactive intermediate, aryldipyrrylmethane-2,9-dicarbinol 13′ that is effectively obtained by sequential reactions of 10 with aroyl chloride and NaBH₄ (Zaidi et al. 2006). This synthetic method using aryldipyrrylmethane and aryldipyrrylmethane-2,9-dicarbinol was applied to A₃B-type porphyrins and AB₂C-type porphyrins. Since aryldipyrrylmethane-2,9-dicarbinol with three different aryl groups 13 was prepared by way of monoacylation of 10 with 2-pyridyl thioester under low temperature, ABCD-type porphyrins 14 were also prepared (Rao et al. 2000; Lindsey 2010).

Fig. 3.5

Synthetic routes to meso-tetraarylporphyrins of various substitution patterns

Dimeric AB₂C-type porphyrin 15 that is known as a gable porphyrin was designed so as to make supramolecular cyclic assembly of six units (Fig. 3.6) (Takahashi and Kobuke 2005). Kobuke and coworkers obtained 2% yield of 15 through TFA-catalyzed mixed condensation of 5-alkyldipyrrylmethane, 1-methylimidazole-2-aldehyde, and isophthalaldehyde. Since preparation yields in the single porphyrin ring-forming reaction which is usually less than 20%, double porphyrin ring-forming reactions would be very low and separation of the target porphyrin is problematic. Reversible coordination of imidazole to Zn allowed reorganization into the cyclic oligomers of 12 porphyrin units. The dimeric porphyrin units of a slipped cofacial orientation constituting the macro ring assembly (15)₆ showed close analogy to the dimeric chlorophyll units assembled in the light-harvesting complexes of photosynthetic bacteria.

Fig. 3.6

Synthesis of a gable porphyrin for modeling a light-harvesting complex

Aida and coworkers reported A₂B₂-type porphyrin 16 in 13% synthetic yield and A₃B-type porphyrin as a byproduct in 4% yield through acid-catalyzed condensation of 5-(2,6-dimethoxyphenyl)-2,3,7,8-tetramethyldipyrrylmethane and benzaldehyde (Fig. 3.7) (Mizuno et al. 2000). The fully substituted porphyrin 16 undergoes a saddle shape distortion of the porphyrin plane in order to relieve steric crowding in its periphery, which results in the introduction of chirality. Although these enantiomeric forms, (M, M)- and (P, P)-form, interconvert rapidly by macrocyclic inversion at room temperature, this conformational change slowed down when they bind two molecules of carboxylic acids. If optically active guests were bound, either one of the diastereomeric pair is favored. For example, a strong CD signal in the negative sign was generated in the visible region (450–500 nm) when (S)-mandelic acid was added to 16 to lead to very high (>98%) diastereoselectivity. Thus, absolute configuration of optically active acids can be determined by the CD Cotton effect due to the porphyrin chromophore. When these diastereomerically biased adducts were dissolved in acetic acid, the chiral guests were replaced by acetic acids to generate enantiomerically biased adducts, the optical purity of which lasts in the timescale of days.

Fig. 3.7

Chirality sensing and optical resolution of carboxylic acids by using trans-A₂B₂-type meso-tetraarylporphyrin of D₂ symmetry

In addition to this chiral memory phenomenon, photoresponsive change in optical purity of the (S)-mandelic acid adduct of 16 was reported in on–off cycles of irradiation of the Soret band. That is, light irradiation caused racemization and the favored original diastereomeric adduct was reassembled in the dark. Crystals generated from a solution of a mixture of 16 and racemic mandelic acid derivatives (1:2.1) were found to be a conglomerate leading to spontaneous optical resolution of the guests (Mizuno et al. 2006).

2.3 Porphyrins with Mixed meso-Substituents

A variety of porphyrins of various meso-substitution patterns can be derivatized from readily available simple porphyrins by introducing meso-substituents and their further transformation as demonstrated by Senge and coworkers (Fig. 3.8) (Senge 2011). trans-A₂-type meso-diarylporphyrins 18 are synthesized conveniently by Lindsey protocol of reacting an equimolar mixture of dipyrrylmethane 17 and aromatic aldehyde with TFA (0.1 equiv) in CH₂Cl₂ followed by DDQ (2 equiv) oxidation. The preparation yields of this 2+2 condensation sometimes amount to ~50% when aromatic aldehydes are not sterically demanding (Senge et al. 2010). Mixed condensation of 17 affords trans-AB-type meso-diarylporphyrins 19, for example, 5-p-tolyl-15-o-anisylporphyrin was prepared in 22% yield (Fig. 3.8) (Senge et al. 2011). Simple procedures for 18 and 19 in relatively good yields provide a practical approach to various meso-substituted porphyrins. cis-A₂-type meso-diarylporphyrins 22 was synthesized by the 3+1 condensation of tripyrrane 21, pyrrole, and aromatic aldehyde in the molar ratio of 1:1:2, for example, 5,10-diphenylporphyrin was prepared in 6% yield. The 2+1+1 condensation of 2-hydroxymethylpyrrole, 17, and aromatic aldehyde gave A-type meso-arylporphyrins 20 that can be converted into cis-AB-type meso-diarylporphyrins 23 by nucleophilic addition of organolithium reagents (Ryppa et al. 2005).

Fig. 3.8

Synthesis of A-type, A₂-type, and AB-type porphyrins

Porphyrin meso-positions undergo ordinary electrophilic substitution reactions such as formylation, nitration, halogenation, and so on. Furthermore, various substituents can be introduced into the meso-position of porphyrin by means of transition metal-catalyzed cross-coupling reactions (Fig. 3.9) (Senge 2011; Ryan et al. 2011). trans-AB-type meso-diarylporphyrins 19 was readily brominated to afford monobromo compound 24 and dibromo compound 25 in good yields. These porphyrins can be subjected to various Pd- or Ni-catalyzed cross-coupling reactions to introduce (hetero)aromatic units by Suzuki coupling and Stille coupling, alkynyl units by Sonogashira coupling, vinyl units by Mizorogi-Heck reaction, and amines by Buchwald–Hartwig reaction. ABC-type meso-triarylporphyrins 26 are obtained in good yields in this way from 24, and these porphyrins were prepared directly from 19 in good yields through the S_NAr reaction. It is noteworthy that alkyllithium reagents work well to introduce a meso-alkyl substituent that is relatively difficult to achieve by metal-catalyzed cross-coupling reactions. The iterative procedures starting from 26 afforded ABCD-type meso-tetraarylporphyrins 29. Dioxaborolanylporphyrin 28 was readily prepared by Pd-catalyzed borylation of bromoporphyrin 27 with pinacolborane (HB(pin)), and it was employed as a coupling partner in the Suzuki coupling, for example, symmetrical meso,meso-linked diporphyrin 30 was synthesized.

Fig. 3.9

Post-introduction of meso-substituents into porphyrin

2.4 meso-Substituted Porphyrins as Photosensitizers

Figure 3.10 illustrates synthesis of a photosensitizer, YD2-o-C8, that showed remarkable solar-to-electric power conversion efficiency (PCE) as used in the dye-sensitized solar cell (DSSC) known as a Grätzel cell (Yella et al. 2011). Since the 11.9% PCE under standard air mass 1.5 G illumination exceeds that of DSSC based on the ruthenium sensitizers, push–pull type porphyrin structures with electron-donating substituents and electron-withdrawing substituents arranged at the periphery are extensively studied. These structures are believed to enhance light-harvesting property that is originated from the intense absorption bands of porphyrins extending from visible to NIR region. Furthermore, introduction of long-chain alkoxy groups was suggested to help suppressing charge recombination process. The Grätzel’s group prepared the trans-A₂BC type porphyrin, YD2-o-C8, as a photosensitizer through Sonogashira coupling, Buchwald-Hartwig amination, and the second Sonogashira coupling, in sequence starting from 5,15-di(2,6-dioctyloxyphenyl)-10-bromoporphyrin 24. Senge and coworkers recently proposed Buchwald-Hartwig amination of 24 as the first step leading to a shorter route to this type of porphyrins (Fig. 3.10) (Meindl et al. 2017). The PCE value of 11.9% of YD2-o-C8 was greater than 8.4% of the reference dye YD2 under the same conditions using Co^II/III tris(bipyridyl) complex as electrolyte (Table 3.1), and their UV–vis absorption spectra have a tailing up to 700 nm with absorption maxima at 442 nm (log ε 5.3), 576 nm (log ε 4.1), and 638 nm (log ε 4.4) in CH₂Cl₂.

Fig. 3.10

Synthesis of trans-A₂BC-type push–pull porphyrins

Table 3.1 Power conversion efficiency (PCE) of Grätzel cell with porphyrin photosesitizers

If cis-A₂- and cis-AB-type meso-diarylporphyrins 22 and 23 are taken as starting materials instead of trans-meso-diarylporphyrins 18 and 19 in Fig. 3.8, porphyrins of additional structural diversity are obtained. Figure 3.11 illustrates synthesis of cis-A₂BC-type porphyrin (ZnPBAT) having two meso-amino substituents by Imahori and coworkers through Sonogashira coupling, Buchwald–Hartwig double amination, and the second Sonogashira coupling, in sequence starting from 5-mesitylporphyrin 20 (Kurotobi et al. 2013). They investigated on the effect of the asymmetrically enhanced push–pull electronic structure on the DSSC performance and found that introduction of the second amino group caused improvement of the light-harvesting efficiency in visible region and 10% increase in the power conversion efficiency when ZnPBAT was compared with YD2 that is substituted with single diarylamino group at the 5-meso position and a 4-carboxyphenylethynyl group at the 15-meso position (Table 3.1) (Bessho et al. 2010).

Fig. 3.11

cis-A₂BC-type push–pull porphyrin of strong intramolecular dipole moment

The Grätzel’s group reported photosensitizers structurally related to YD2-o-C8. Insertion of a 2,1,3-benzothiadiazole unit between the benzoic acid anchoring group and ethyne linker improved PCE performance in the case of GY50 (Yella et al. 2014). Since 2,1,3-benzothiadiazole is strongly electron-withdrawing group, enhanced push–pull effect of GY50 caused red-shift of the absorption bands with more coverage of the visible to NIR wavelength region. Significantly reduced PCE in GY21 indicated that the benzene spacer between the 2,1,3-benzothiadiazole and carboxylic acid plays a key role in suppressing back electron transfer. When the electron-donating effect was strengthened by introducing 2,4-dialkoxyphenyl group at the 5-diarylamino substituent in the case of SM315, 13% PCE was achieved (Mathew et al. 2014). Relationship between photosensitizer structure and PCE is summarized in Table 3.1.

Water-soluble porphyrin, as a photosensitizer, transfers excitation energy to generate singlet molecular oxygen ¹O₂ that is cytotoxically leading to cell death in photodynamic therapy (PDT) of cancer (Sternberg and Dolphin 1998). Anderson reported A₂BC-type porphyrin 31 that was designed for high intracelluar uptake (Fig. 3.12) (Kuimova et al. 2009). The butadiyne-linked diporphyrin structure of 31 causes conformational change between a planar form and a less stable twisted form through the rotation around the butadiyne axis. The ratio of these conformers was found to depend on the viscosity of the media that was detected by their distinctive fluorescence at 780 nm of the planar form and at 710 nm of the twisted form. The content of the twisted form was found to increase as increase in viscosity, this is because the rotation around the butadiyne axis becomes slower in viscous media. This fluorescent ratiometric molecular rotor provides insight into the diffusion-mediated cellular processes. They found that the diporphyrin 31 incorporated into live cells caused significant increase in the viscosity of the intracellular environment upon irradiation of light. This was interpreted in terms of the crosslinking reactions induced by singlet oxygen generated by the photosensitizing effect of 31.

Fig. 3.12

Butadiyne-linked diporphyrin as a fluorescent ratiometric molecular rotor

Porphyrin-related compounds have been widely studied in the field of PDT due to their intense absorption at long-wavelength visible region that leads to ¹O₂ generation by way of the triplet excited state due to effective intersystem crossing (Sternberg and Dolphin 1998). Important improvements of the photobiological effect depend on photosensitizers excited by photoirradiation at NIR region (700–1300 nm), because the NIR light can penetrate deeply into the biological tissues. The two-photon absorbing photosensitizers can be photo-excited by intense laser pulses at NIR region and the pinpoint focus of the laser beam enables treatment in the deep area of tissues. Therefore, porphyrin compounds of high two-photon absorption (2PA) efficiency have been extensively studied. The 2PA efficiency is estimated by 2PA cross section (σ) in the unit of GM as the ordinary one-photon absorption depends on the molecular extinction coefficient (ε). Push–pull porphyrin structure with extended π-conjugation is thought to have great magnitude of 2PA cross section as well as in the case of DSSC. Although simple monomeric porphyrins exhibit very small 2PA cross section less than 50 GM with femto-second pulses, the diporphyrin 31 showed a very high 2PA cross section of 17,000 GM with femto-second pulses at 916 nm and its 2PA PDT effect was demonstrated in vivo (Collins et al. 2008).

In the template-directed synthesis of cyclic porphyrin oligomers developed by Anderson and coworkers (Bols and Anderson 2018), 5,15-diarylporphyrin 18 as a starting material was brominated and then subjected to Pd-catalyzed Sonogashira coupling with trialkylsilylacetylene to give 5,15-diaryl-10,20-diethynylporphyrin 32 after desilylation (Fig. 3.13) (Sprafke et al. 2011). In the presence of properly designed template, Glacer oxidative dimerization of the ethyne units was successfully accomplished to give π-conjugated macro ring. The cyclic hexamer of Zn porphyrin cyclo-(32)₆ with butadiyne spacers was formed in 21% yield as a 1:1 complex with hexapyridine template T₆. The fluorescence spectrum of cyclo-(32)₆ •T₆ showed NIR bands ranging from 900 to 1300 nm, and the excited state delocalized over the whole macro ring was generated within less than 0.5 ps after the light absorption.

Fig. 3.13

Template-directed synthesis of π-conjugated cyclohexamer of Zn porphyrin

The dimeric porphyrin 33 worked well in this Glacer homocoupling reaction to afford the same macrocycle in better yield (Fig. 3.14). Although a small amount of the cyclododecamer was formed as a byproduct in these cyclization reactions, the Glacer reaction of the butadiyne-linked linear tetramer 34 in the presence of T₆ as a mismatch combination for the cyclo-(32)₆ generated, in 39% yield, a cyclic porphyrin dodecamer cyclo-(34)₃ that includes two template molecules inside the cavity (Kondratuk et al. 2014). A smaller hexapyridine template T’₆ having a hexaethynylbenzene core instead of the hexaphenylbenzene core of the T₆ template was used in the cyclization of ethyne-linked linear oligomers of porphyrin (Rickhaus et al. 2017). The linear ethyne-linked porphyrin hexamer 35 was subjected to Sonogashira coupling reaction to give a 1:1 complex, cyclo-35•T’₆, in 15% yield. A tetrapyridine template T’₄ has a tetraethynylbenzene core and worked well in the cyclization of the linear ethyne-linked porphyrin octamer 36 by Sonogashira coupling to give a 1:2 complex, cyclo-36•(T’₄)₂, in 32% yield. The fluorescence band of cyclo-35•T’₆ at 1073 nm is red-shifted relative to that of the linear hexamer, linear-35, at 909 nm and the fluorescence quantum yield of cyclo-35•T’₆ is smaller by the factor of 1000, which is indicative of the highly delocalized singlet excited state of the cyclohexamer.

Fig. 3.14

Template-directed synthesis of π-conjugated cyclooligomers of Zn porphyrin

Anderson, Rebane, and coworkers studied two-photon absorption efficiency of their π-conjugated oligomers (Drobizhev et al. 2006). The 2PA cross section values (σ) of the linear Zn porphyrin oligomers increased by 450 times upon going from the monomer 32(SiR₃)₂ to the dimer 33(SiR₃)₂, but only by 2.4 times from the dimer 33(SiR₃)₂ to the tetramer 34(SiR₃)₂. The σ value increased gradually from 22,000 GM to 37,000 GM when the porphyrin units increased from 4 to 8 in a series of butadiyne-linked linear oligomers end-capped with trialkylsilyl groups. The 2PA cross section of cyclo-(32)₆ •T₆ determined by femto-second 2P fluorescence intensity with laser pulses at 1000 nm was 151,000 GM that is much greater than 23,000 GM for the linear hexameric porphyrin oligomer of 32 end-capped with trialkylsilyl groups (Mikhaylov et al. 2016). This great σ value is responsible for the effective π-conjugation over the whole ring that is promoted by the complexation of the template.

3 Porphyrins Substituted at Pyrrole β-Positions

3.1 Barton–Zard Pyrrole Synthesis

A number of porphyrins with substituents at the pyrrole β-positions are derived from β-substituted pyrroles. Among many synthetic methods for pyrrole ring such as classical Knorr pyrrole synthesis, Barton–Zard synthesis is frequently used because of generality, applicability, and simple procedure. Nitro olefins are generated from nitroaldol products (acetoxynitroalkanes 37) in situ under basic reaction conditions of Barton–Zard synthesis and then undergo [3+2]-cycloaddition with isocyanoacetate to give 3,4-disubstituted pyrrole-2-carboxylate 38 (Fig. 3.15) (Barton and Zard 1985). The ester function at one of the pyrrole α-positions is regarded as a protecting group, and it can be easily removed or utilized as a meso-carbon of porphyrin structure leading to versatile application. A related methodology, van Leusen pyrrole synthesis, using tosylmethyl isocyanide (TosMIC) and Michael acceptor is useful in the synthesis of 3,4-disubstituted pyrroles 39 having electron-withdrawing groups (EWG) at the β-position (van Leusen et al. 1992). 2-Stannylpyrrole 40 was also obtainable in good yields by one-pot procedure, and it is useful in the Stille coupling reactions leading to various building blocks for porphyrin analogues (Dijkstra et al. 1998).

Fig. 3.15

Barton–Zard pyrrole synthesis and van Lausen pyrrole synthesis

Naturally occurring porphyrins have alkyl substituents at all the pyrrole β-positions. These 2,3,7,8,12,13,17,18-octaalkylporphyrins are different from 5,10,15,20-tetraarylporphyrins in their stereochemistry, electronic structure, and reaction behavior. 2-Carboethoxy-3,4-diethylpyrrole 38 was readily decarboxylated and then subjected to the ordinary porphyrin synthesis using formaldehyde to give octaethylporphyrin (OEP) 41 in 30% yield (Sessler et al. 1992). Ponomarev and coworkers reported that Vilsmeier formylation of OEPCu(II) followed by NaBH₄ reduction produced meso-(dimethylaminomethyl)OEPCu(II) 42 in good yield. When 42 was allowed to react with MeI, ethylene-bridged diporphyrin 43 was obtained as a bisCu(II) complex (Fig. 3.16) (Borovkov et al. 1999). Binding optically active guest molecule by cooperative metal–ligand coordination bondings forces the bisZn(II) complex to take the face-to-face and skewed orientation of their porphyrin rings. Supramolecular chirogenesis of the bisZn(II) complex was extensively studied in the chirality sensing by Borovkov, Inoue, and coworkers (Borovkov et al. 2004).

Fig. 3.16

Octaethylporphyrin and ethylene-bridged porphyrin

Ono, Uno, and coworkers used a Diels–Alder adduct 44 as a nitro olefin equivalent in the Barton–Zard pyrrole synthesis to give ethanoisoindole 45 (Fig. 3.17) (Uno et al. 2000). Phenylsulfenyl chloride addition, MCPBA oxidation, and HCl elimination proceeded in the transformation from 45 to 46. This reaction sequence is of great importance because simple alkenes are almost quantitatively converted into substrates for Barton–Zard pyrrole synthesis. Diels–Alder adduct 48 between cyclobutadiene and dimethyl acetylenedicarboxylate was also converted to the phenylsulfonyl olefin 49 (Ito et al. 1998, 2001). The phenylsulfonyl olefins 46 and 49 are reactive as well as nitro olefin to give the corresponding pyrroles 47 and 50 in more than 80% yield. These pyrroles were designed to liberate ethylene on pyrolysis by retro Diels–Alder reaction to generate benzo units in the final step of porphyrin synthesis.

Fig. 3.17

Barton–Zard synthesis of [2,2,2]-octadiene-fused pyrroles

Sulfolene as an inexpensive butadiene precursor was conveniently employed by Finikova, Vinogradov, and coworkers in the Diels–Alder reaction to give dicarbomethoxycyclohexene 51. This Diels–Alder adduct was then converted to phenylsulfonyl cyclohexene 52 and subsequently to the tetrahydroisoindole 53 by Barton–Zard reactions (Finikova et al. 2001). When cyclohexene was taken as a starting material, the α-free pyrrole 54 was also obtained in good yield (Fig. 3.18) (Finikova et al. 2004). These cyclohexene-fused pyrrole units are readily converted into the benzene-fused pyrrole units by oxidation under mild reaction conditions especially after porphyrin ring formation.

Fig. 3.18

Barton–Zard pyrrole synthesis using cyclohexene

3.2 Benzoporphyrins

Tetrabenzoporphyrins where benzene rings are fused at the pyrrole β-positions are chemically stable, and their extended π-conjugation stabilizes their cationic states, which changes the basicity and redox potentials. In addition to these features, the red-shifted UV–vis absorption spectra of benzoporphyrins are suitable as optoelectronic materials. The above-mentioned pyrroles 45, 50, 53, and 54 are important building blocks for benzoporphyrins. Since the highly planar benzoporphyrins tend to form a face-to-face stacked array leading to insoluble materials, purification is usually difficult. The precursor porphyrins substituted with aliphatic groups at the pyrrole β-positions were prepared in 30–40% yield from the corresponding pyrroles by condensation with formaldehyde and aryl aldehydes. These porphyrins can be dissolved in organic solvents and circumvent problems associated with low solubility of benzoporphyrins (Fig. 3.19) (Carvalho et al. 2013). High temperature at ~200 ℃ is needed to induce retro Diels–Alder reaction in the pyrolysis as the final step to tetrabenzoporphyrins 55 and 56 starting from 45 and 50 (Ito et al. 1998, 2001). These porphyrins were alternatively obtained in good yields under much milder reaction conditions by oxidative aromatization starting from 53 and 54, but oxidizing agents like metal salt, DDQ, or acid are needed (Finikova et al. 2001, 2004). The retro Diels–Alder method allows preparation of device assemblies of benzoporphyrins by introducing precursor porphyrins into the device assemblies before pyrolysis.

Fig. 3.19

Synthesis of benzoporphyrins

In the UV–vis spectrum of meso-unsubstituted benzoporphyrin 56 (Z = H), the Soret band at 454 nm and the Q band at 648 nm are red-shifted by 49 nm and 84 nm, respectively, relative to the bicyclo[2.2.2]octadiene-fused precursor (Table 3.2). In particular, this Q band of 56 (Z = H) is very strong with its absorption coefficient being in the order of 10⁵ M⁻¹ cm⁻¹ (Ito et al. 2001). UV–vis absorption bands of meso-tetraphenylbenzoporphyrin 56 (Z = Ph) are further red-shifted by ~30 nm relative to 56 (Z = H).

Table 3.2 Selected major UV–vis absorption bands of benzoporphyrins

Uno and coworkers prepared bicyclo[2.2.2]octadiene-fused dimeric porphyrin 57 in 21% yield using double 3+1 condensation of tripyrrane and the dipyrrole derived from 47 (Fig. 3.20). Subsequent retro Diels–Alder reaction afforded benzene-fused dimeric porphyrin 58 (Uno et al. 2007). The strong Soret band of 58 (M = 2Zn) at 475 nm is significantly red-shifted from those (399 nm and 414 nm) of 57 (M = 2Zn) (Table 3.2). The Q band of 58 at 638 nm is as intense as the Soret band and red-shifted by 64 nm in comparison with weak Q bands of 57 at 533 nm, and 574 nm. The single 3+1 condensation of tripyrrane and dipyrrole 47 followed by reduction of the ester group gave bicyclo[2.2.2]octadiene-fused porphyrin 59 in 18% yield. The pyrrole-2-carbinol part of 59 reacted under ordinary reaction conditions of porphyrin synthesis to give 24% yield of the pentameric porphyrin 60 where four porphyrin rings are connected to the pyrrole β-positions of the central porphyrin ring. Pyrolysis of 60 proceeded almost quantitatively to generate cruciform porphyrin 61 that has overall π-conjugation among 5 porphyrin units (Uoyama et al. 2010).

Fig. 3.20

Benzene-fused multiporphyrins

The UV–vis spectrum of 61 (M = 5Zn) showed strong Soret bands at 415 nm and 498 nm. These Soret bands are red-shifted from those (404 nm and 423 nm) of 60 (M = 5Zn) (Table 3.2). The Q band of 61 (M = 5Zn) at 763 nm is as intense as the Soret band and far red-shifted in comparison with weak Q bands of 60 (M = 5Zn) at 534 nm, and 573 nm and also with the Q band (638 nm) of the benzene-fused dimeric Zn porphyrin 58 (M = 2Zn), whereas the UV–vis spectra of bicyclo[2.2.2]octadiene-fused oligomeric Zn porphyrins 57 and 60 are not so different from that of monomeric Zn porphyrin.

Two-photon absorption cross section provides information on how far the π-conjugation is expanding in the molecular systems. The 2PA cross section values of the benzene-fused oligomeric Zn porphyrin 58 (M = 2Zn) and 61 (M = 5Zn) measured by z-scan method were reported as 3000 GM (λ_ex 1275 nm) and 3900 GM (λ_ex 1500 nm), respectively (Uoyama et al. 2010). These values are much larger than those (<100 GM) of monomeric porphyrins, but they are less than those (10⁴–10⁵ GM) of meso,meso-butadiyne-linked multiporphyrins like 33(SiR₃)₂ and 34(SiR₃)₂. It was suggested that electronic interaction between porphyrin π-systems by way of the pyrrole β-positions is not so effective as by way of the meso-positions.

Smith and coworkers prepared the cruciform porphyrin having four meso-tetraphenylporphyrin units instead of meso-unsubstituted porphyrin units of 61 in a simple procedure (Jaquinod et al. 1998). The phenylsulfonyl group was introduced into sulfolene itself through phenylsulfenyl chloride addition, MCPBA oxidation, and HCl elimination and then subjected to the Barton–Zard pyrrole synthesis. Pyrolysis of the resulting sulfolene-fused pyrrole 62 at 240 ℃ in the presence of meso-tetraphenylporphyrin (TPP) produced pyrroloporphyrin 64 in ca. 30% yield after DDQ oxidation of the initially formed pyrrolochlorin 63 (Fig. 3.21). The pyrroloporphyrin 64 was reduced to the corresponding carbinol that is an analogue of 59 and then converted into the cruciform porphyrin after DDQ oxidation.

Fig. 3.21

TPP-derived building block of cruciform porphyrin

Smith and coworkers also used meso-tetraphenylporphyrin (TPP) as a starting material in the synthesis of directly β-fused porphyrin trimer 66 (Fig. 3.22) (Paolesse et al. 2000). Readily available mononitroTPPNi(II) was regarded as a substrate for the Barton–Zard synthesis and it actually gave pyrroloporphyrin 65 after decarboxylation. It is noteworthy that β-nitroporphyrins react in a similar fashion to nitroalkene. Bisquarternary ammonium salt derived from 2,5-bis(N,N-dimethylaminomethyl)pyrrole was allowed to react with 65 under neutral conditions in the presence of oxidizing agent to afford 18% yield of the target porphyrin 66. This β-fused trimer showed intense UV–vis bands at 486 nm (log ε = 5.3) and 716 nm (log ε = 5.2).

Fig. 3.22

Directly linked trimeric porphyrin

Kräutler and coworkers obtained sulfolene-fused porphyrin 67 in 44% yield by ordinary condensation reaction of arylaldehyde and solfolene-fused pyrrole that is derived from 62 (Fig. 3.23). Pyrolysis of 67 at 140 ℃ in the presence of 1,4-benzoquinone induced [4+2] cycloaddition and subsequent DDQ oxidation and metal insertion generated tetrabenzoporphyrin 68 with further π-conjugation to the quinone moieties (Banala et al. 2009). Fusion of 1,4-naphthoquinone instead of benzene at the pyrrole β-positions of meso-tetraarylporphyrin caused red-shifts of the Soret band by ~90 nm and of the Q band by ~70 nm in their UV–vis spectra (the major absorptions at 555 nm and 725 nm) of 68 in chlorinated solvents. 68 is a black-colored porphyrin with the lowest absorption coefficient (8700 M^–1 cm^–1) over the whole UV–vis range (230–770 nm) seen as an absorption valley at 634 nm.

Fig. 3.23

A black-colored 1,4-naphthoquinone-fused porphyrin

Organometallic synthetic methods were applied in synthesizing benzoporhyrins by way of brominated meso-tetraarylporphyrins 69 and 70 that were obtained by using N-bromosuccinimide (NBS). Tetrabromination occurs regioselectively at the opposite pyrrole rings of the meso-tetraarylporphyrin free base in ~60% yield and octabromination of the Ni complexes proceeds in more than 80% yield (Chumakov et al. 2009). Water-soluble porphyrins are useful especially in the biomedical application, and meso-tetraarylporphyrins where four meso-aryl groups are pyridinium or aryl sulfonate have been frequently studied. Highly water-soluble porphyrins with eight hydrophilic groups at all the pyrrole β-positions have been synthesized recently through one-pot three-step reactions of Cu, Ni, and Zn complexes of 69 and vinylpyridines using Pd catalyst in 46–54% yields (Fig. 3.24) (Jiang et al. 2012). These metal complexes of meso-tetraaryltetrabenzoporphyrin 71 (M = Zn) can be protonated at the eight pyridyl units, which caused red-shifts by ~30 nm of the Soret band to 525 nm and the Q band to 708 nm. The Q band at 684 nm of the protonated complex of 71 (M = Ni) showed unusually high intensity as a monomeric metalloporphyrin. This octacation of 71 could be dissolved in distilled water with concentration more than 15 mM. When the tetrabromoporphyrin 70 was allowed to react with methyl acrylate under similar reaction conditions, the one-pot reactions of Mizorogi-Heck coupling, 6π-electrocyclization, and oxidative aromatization occurred to give the dibenzoporphyrin 72 with four methyl ester units in 58% yield. 72 was converted into the Zn(II) tetrabromodibenzoporphyrin in 42% yield and then subjected to the Pd-catalyzed coupling reaction with 4-methoxystyrene under the same Mizorogi-Heck conditions. The Zn(II) tetrabenzoporphyrin 74 formed in 45% yield was further converted to the push–pull porphyrin 75 with two benzenedicarboximide units as electron-withdrawing groups and two 3,4-di-p-anisylbenzene units as electron-donating groups (Kumar et al. 2018).

Fig. 3.24

Water-soluble porphyrin and push–pull porphyrin

The push–pull tetrabenzoporphyrin Zn complex 75 showed the Soret absorption band at 507 nm that is red-shifted by 51 nm in comparison with the dibenzoporphyrin Zn complex of 73 with two 3,4-di-p-anisylbenzo units. It is also red-shifted by 30 nm in comparison with the dibenzoporphyrin Zn complex with two benzenedicarboximide unit derived from 72. The Q band of 75 at 721 nm appeared at by ca. 80 nm longer wavelength than those push-only or pull-only dibenzoporphyrins. Theoretical study on the electronic structure indicated that the HOMO–LUMO gaps of the push-only and pull-only dibenzoporphyrins are not so different although both HOMO and LUMO energy levels of the push-only dibenzoporphyrin are higher than those of the pull-only dibenzoporphyrin. It is of interest that the HOMO energy level of 75 is very similar to that of the push-only dibenzoporphyrin and the LUMO energy level of 75 is very similar to that of the pull-only dibenzoporphyrin, which significantly reduced the HOMO–LUMO gap. This result was consistent with the cyclic voltammetric analysis; 1.75 V for 75 is by 0.25 V smaller than those dibenzoporphyrins.

3.3 Reactions of Porphyrins at Pyrrole β-Positions

Since meso-tetraarylporphyrins are readily available, robust, and soluble in organic solvents, great effort has so far been directed to structural modification at pyrrole β-positions. Bringmann and coworkers investigated Pd-catalyzed borylation of 2-bromo-meso-tetraphenylporphyrin 76 and obtained β-dioxaborolanylporphyrin 77 in 70% yield using toluene–water two phase system (Fig. 3.25) (Bringmann et al. 2008). If this reaction was run in DMF, carbopalladation on the adjacent meso-phenyl group occurred to give almost exclusive formation of indene-fused porphyrin 78 without participation of bis(pinacolato)diboron (B₂(pin)₂) in the reaction. A closely related cyclopentadiene-fused porphyrins 80 was reported by Osuka’s group through Pd-catalyzed reaction between meso-bromoporphyrin 79 and alkynes (Sahoo et al. 2006). The Ni and Cu complexes 80 showed split Soret bands; one at 380–390 nm and the other at 480–490 nm. The additional π-conjugation in 80 (M = Ni) decreased electrochemical HOMO–LUMO gap (ΔE = 1.66 V) relative to that (ΔE = 2.29 V) of trans-A₂ type diarylporphyrin Ni complex. Once β-borylated porphyrin 77 was available, it was subjected to the Pd-catalyzed Suzuki–Miyaura cross coupling with 76 leading to β,β-linked diporphyrin 81 in 73% yield. Some bimetallic complexes of 81 could be resolved into enantiomers by HPLC on a chiral phase. The rotational stability at the β,β-axis depends on the metal but racemization of the optically resolved bisZn complex was not seen at room temperature.

Fig. 3.25

Borylation of porphyrins

Osuka, Shinokubo, and coworkers reported that the pyrrole β-position adjacent to the unsubstituted meso-position could be directly borylated (Hata et al. 2005). When the [Ir(COD)OMe]₂-catalyzed direct borylation of aromatic compounds by B₂(pin)₂ was applied to 5,15-diarylporphyrin and 5,10,15-triarylporphyrin, the 3,3,4,4-tetramethyldioxaborolanyl group was introduced selectively through the C-H activation at the pyrrole β-position that is sterically less congested than the meso-position. By changing the B₂(pin)₂/porphyrin ratio, monoborylated and diborylated porphyrins (82, 83, 84) were obtained in 43–82% yield. These borylated porphyrins were conveniently employed for various Pd-catalyzed cross-coupling reactions.

The pyrrole β-position of meso-tetraarylporphyrins is functionalized by oxidation reactions (Fukui et al. 2017). Brückner, Rettig, and Dolphin reported that OsO₄-mediated cis-dihydroxylation of TPPH₂ and TPPNi(II) gave 2,3-dihydroxy-meso-tetraarylchlorin 87 in 49% and 72% yield, respectively (Fig. 3.26) (Brückner et al. 1998). These compounds were further oxidized by DDQ to generate 2,3-dioxochlorins 88 in 73 and 65% yield (Daniell et al. 2003). 88 was alternatively synthesized by Crossley and coworkers by oxidizing β-amino- and β-hydroxyporphyrin 85 and 86 that were prepared conveniently from β-nitroporphyrin (Crossley and King 1984; Crossley et al. 1991). The Crossley’s group utilized this 2,3-dioxochlorin 88 as a key compound in the development of various porphyrin oligomers of extended π-conjugation. The dimeric porphyrin 90 (n = 0) that was prepared by condensation of 88 with 1,2,4,5-tetraaminobenzene was converted to the 12,12′,13,13′-tetraoxobischlorin and then reacted with 1,2,4,5-tetraaminobenzene and 88 at both ends. Thus formed tetrameric porphyrin 90 (n = 2) showed electrochemical HOMO–LUMO gap of 0.8 eV (Crossley and Burn 1991). Brückner and coworkers obtained a pyrrole-modified porphyrin called indaphyrin 91 from 2,3-dihydroxy-meso-tetraarylchlorin 87 under acidic aerobic conditions (McCarthy et al. 2004). That is, a secochlorin bisaldehyde intermediate formed by the oxidative C–C bond cleavage of the vicinal diol part of 87 with sodium periodate undergoes Friedel–Crafts type aromatic substitution at the meso-phenyl ortho-position promoted by trifluoroacetic acid (TFA).

Fig. 3.26

Oxidative functionalization at the pyrrole β-position

Indaphyrin 91 and its metal complexes have a helical conformation in order to relieve electronic repulsion of carbonyl oxygens to one another and each resolved enantiomer was quite stable with a racemization barrier greater than 113 kJ/mol at 25 ℃. UV–Vis spectrum of 91 and its metal complexes show broad absorptions in the region between 400 and 600 nm. Free base 91 has split Soret-like bands at 419 nm and 554 nm with ε = ~4 × 10⁴ (Samankumara et al. 2015; Götz et al. 2015). α-Keto oximes 89 formed from metal complexes 88 (M = Ni, Pd, Pt) of 2,3-dioxochlorins readily underwent Beckmann rearrangement with p-toluenesulfonic acid (TsOH), in which case the pyrrole-3-oxo-4-oxime part was converted into 6-membered pyrazine imide in the product 92 (Akhigbe and Brückner 2013).

4 π-Extended Porphyrins

4.1 Electrophilic Substitution with meso-Aryl Groups

π-Extension of porphyrin core causes great influence on the absorption bands and redox potentials, which extends the applicability of porphyrin compounds to various scientific fields. Porphyrins with meso-acetylene groups (appeared in 3.1.4), benzoporphyrin derivatives (appeared in 3.2.2), and linear oligomers 66 and 90 are examples of this category. π-Conjugation between meso-aryl groups and porphyrin core could be enabled by simple procedure as already mentioned in the compounds 78, 80, and 91.

Callot and coworkers used Friedel–Crafts acylation as a key reaction in connecting meso-aryl ortho-positions and pyrrole β-positions (Fig. 3.27) (Richeter et al. 2003). cis-A₂B₂ type meso-tetraarylporphyrin 93 was obtained in 5.1% yield from the porphyrin products mixture in the mixed condensation of pyrrole, o-methoxycarbonylbenzaldehyde, and 3,5-di-t-butylbenzaldehyde in the ratio of 2:1:1. The ester group of 93 was converted into acid chloride and then subjected to Friedel–Crafts reaction conditions. The major product 94 obtained in 44% had bistetralone-fused porphyrin structure. The Soret band at 516 nm (log ε = 4.9) and the Q band at 738 nm (log ε = 4.1), 826 nm (log ε = 4.1) in the UV–vis spectrum were remarkably red-shifted. A mixture of 2,12- and 2,13-dibromoTPPH₂ 95 obtained by regioselective dibromination of TPPH₂ was reacted with CuCN to give di-cyanoTPPCu 96 effectively by nucleophilic aromatic substitution. Hydrolysis of the cyano group followed by a similar Friedel–Crafts procedure afforded differently bistetralone-fused porphyrins 97 and 98 in 27% and 30% yield, respectively, after chromatographic separation.

Fig. 3.27

Friedel–Crafts acylation between the meso-aryl o-position and the pyrrole β-position

Brückner’s group also showed that if α-keto oxime free base 89 was reacted with TsOH, the Beckmann rearrangement leading to 92 was suppressed and the adjacent meso-phenyl group participated to generate a quinoline ring leading to mono- and bisquinoline-fused porphyrins 100 and 103 (Fig. 3.28) (Akhigbe et al. 2015). These pyrrole-modified porphyrins were alternatively synthesized in better yields through DDQ oxidation of the oxime moiety of 89 and 100 by way of mono- and bisquinoline N-oxide 99 and 101. These quinoline-fused porphyrin free bases show Q bands in the range of 730–780 nm. Ruppert and coworkers reported that the bisquinoline-fused porphyrin 103 was regarded to have an external bidentate coordination site and can be obtained in a shorter synthetic route starting from readily available β-nitroporphyrin (Jeandon and Ruppert 2011). meso-Phenyl C-H insertion of nitrene generated from nitro group with triethyl phosphite afforded dihydroquinoline-fused porphyrin 102 effectively. Protection of the NH group and nitration of 102 followed by just heating produced 103 in good yield.

Fig. 3.28

Pyrrole-modified porphyrins with quinoline-fusion

4.2 Oxidative Coupling of β-Aminoporphyrins

β-Aminoporphyrins were readily prepared and showed interesting reactions that are owing to their nature of being easily oxidized. β-Amino-meso-tetraarylporphyrins 85 were conveniently applied to synthesizing dimeric porphyrins (Fig. 3.29). Bringmann and coworkers intended to obtain β,β-linked diporphyrin 104 by Ullmann coupling of 2-amino-3-bromoporphyrin 105, but the product obtained in 78% yield turned out to be pyrazine-fused diporphyrin (M = Ni) 106 (Bruhn et al. 2014). The β,β-linked diporphyrin 104 was formed from 85 (M = Ni) in 94% yield by oxidizing with AgPF₆. 104 is intrinsically chiral diporphyrin, and its conformational change by rotation around the β,β-axis is inhibited even at 100 ℃. In comparison with the bisNi complex of diporphyrin 81, stereochemical stability is significantly increased by the presence of amino groups. The pyrazine-fused diporphyrin 106 (M = Zn) was also synthesized by Mandoj, Paolesse, and coworkers by reacting 2,3-diamino-meso-tetraphenylporphyrin 107 with 2,3-dioxochlorin 88 or diethyl oxalate (Mandoj et al. 2013). Shinokubo and coworkers recently investigated DDQ oxidation of β-aminoporphyrins 85 (M = Ni) with bulky meso-tetraaryl groups and found formation of the pyrazine-fused diporphyrin 108 in high yields (Ito et al. 2015). Although meso-tetraphenyl derivatives 106 take C_2h symmetric conformation, meso-tetramesityl derivative 108 has twisted π-conjugation system of D₂ symmetry. The bisZn complex 109 is interchanging rapidly between a (M, M)-form and a (P, P)-form and binding (R)-1-phenylethylamine induced helical sense bias in favor of the (M, M)-form with 65:35 diastereoselectivity (Ito et al. 2016).

Fig. 3.29

Oxidative dimerization of aminoporphyrins

Fujimoto and Osuka demonstrated that π-conjugation between two porphyrin cores is much more enhanced by 1,5-naphthyridine-fusion in comparison with the pyrazine-fusion seen in 106 (Fujimoto and Osuka 2018). The 1,5-naphthyridine-fused diporphyrin 112 was obtained in 84% yield by Pt(II)-catalyzed cyclization of bisNi(II) complex of β-to-β ethynylene-bridged meso-aminoporphyrin dimer 111 followed by oxidation with PbO₂ (Fig. 3.30). Ni(II) complex 111 was prepared starting from β-borylporphyrin 83 by NIS-CuI iodination, (Fujimoto et al. 2014) Sonogashira coupling, nitration with AgNO₂-I₂, and reduction with NaBH₄-Pd/C. The UV–vis major band of 106 (M = Zn) appears at 492 nm (log ε = 5.06) and their Q bands are at shorter wavelength region than 650 nm. Its electrochemical HOMO–LUMO gap is 2.16 V that is only slightly smaller than 2.24 V of TPPZn. In contrast, the HOMO–LUMO gap (0.99 V) of 112 measured by cyclic voltammetry is remarkably smaller than the reduced form 113 (1.8 V). The major absorption bands of 112 at 521 nm (log ε = 5.1) and 1011 nm (log ε = 5.0) are far red-shifted in comparison with those (496 and 663 nm) of 113 (Table 3.3).

Fig. 3.30

1,5-Naphthyridine-fused diporphyrin

Table 3.3 UV–vis and near-infrared absorption bands of π-extended porphyrins and their electrochemical HOMO–LUMO gap

4.3 Oxidative Fusion of Porphyrin Periphery

Oxidative coupling of aromatic rings with dehydrogenative C–C bond formation is a versatile method for extending π-conjugation (Grzybowski et al. 2013). This Scholl type oxidation has been applied to porphyrin compounds (Lewtaka and Gryko 2012). Stepien and coworkers introduced phenanthrene units at the periphery of porphyrin using Scholl type oxidation (Fig. 3.31) (Mysłiwiec et al. 2012). 3,4-Diarylpyrrole that was prepared by Barton–Zard reaction was converted to octakis(3,4-dialkoxyphenyl)porphyrin 114 in 62% yield. Scholl oxidation of the Zn complex of 114 with FeCl₃ proceeded to give 97% yield of the tetraphenanthroporphyrin 115. This efficient transformation to highly π-extended porphyrin 115 is noteworthy. The π-extension caused red-shift of the Soret band from 427 to 474 nm, and the maximum Q band intensity increased from 4.38 (log ε at 522 nm) to 4.90 (log ε at 650 nm). The electrochemical HOMO–LUMO gap decreased from 2.27 to 1.66 V upon going from 114 to 115.

Fig. 3.31

Scholl oxidation to tetraphenanthroporphyrin

More effective π-extension is enabled by oxidative aromatic coupling between meso-aryl groups and porphyrin core (Fig. 3.32). Osuka and coworkers obtained Ni(II) meso-tetraazulenylporphyrin 116 and then it was successfully converted to the fully azulene-fused porphyrin 117 by FeCl₃-mediated oxidation. The special ester substituents (2,4,6-tri-t-butylphenyl ester) allowed clean oxidation in 60% yield (Kurotobi et al. 2006). The Ni complex 117 showed strong absorption bands at 684 nm (log ε = 4.8) and 1136 nm (log ε = 4.7) (Table 3.3). This significantly red-shifted spectrum, and the well diminished electrochemical HOMO–LUMO gap (1.01 V) illustrate the great effect of azulene fusion. The 2PA cross section value (σ = 7170 GM) of 117 measured at 1380 nm excitation was very high as a monomeric porphyrin (Pawlicki et al. 2009). The quadruply fused Ni porphyrin 119 was also prepared by Anderson and coworkers (Davis et al. 2011). The eightfold oxidative ring closure occurred at the pyrrole-β-positions of Ni(II) meso-tetra-9-anthracenylporphyrin 118 that was prepared by condensation of 9-anthracenyl-2-pyrrylmethanol. It is remarkable that the Q band of 119 appeared at extremely long wavelength (1417 nm) with a remarkable intensity (log ε = 5.07) that is greater than the Soret-like absorption at 842 nm (log ε = 4.85) (Table 3.3). The electrochemical HOMO–LUMO gap of 0.61 V was very small.

Fig. 3.32

Quadruply azulene- and anthracene-fused porphyrins

Scholl type oxidation was applied to introduce direct triple bridges between two porphyrin cores of meso-triarylporphyrins (Fig. 3.33). Thompson and coworkers oxidized 5,15-diaryl-10-pyrenylporphyrin Zn(II) complex 120 with DDQ-Sc(OTf)₃ to give β,β-, meso,meso-, β’,β’-triply fused diporphyrin 121 (Diev et al. 2010). This diporphyrin was further oxidized with FeCl₃ to cause oxidative coupling between meso-pyrenyl groups and pyrrole β-positions. The fully fused Zn complex 122 showed the major absorptions at 618 nm (log ε = 5.24) and 1323 nm (log ε = 5.05). This NIR band of 122 is red-shifted by 182 nm and the electrochemical HOMO–LUMO gap (0.84 V) of 122 decreased by 0.25 V in comparison with those of 121 (Table 3.3). Kim and coworkers studied this oxidation chemistry of meso-triarylporphyrin 123 having a N-annulated perylene group instead of a pyrenyl group of 120 (Luo et al. 2015). The fully fused diporphyrin 124 showed the major absorptions at 657 nm (log ε = 5.05) and 1322 nm (log ε = 5.16) and a HOMO–LUMO gap of 0.62 V. Anderson’s group also reported similar oxidative fusion in the case of meso-triarylporphyrin 125 having a 9-anthracenyl group (Davis et al. 2010). The fully fused diporphyrin 126 showed intense absorptions at 665 nm (log ε = 5.26) and 1495 nm (log ε = 5.16) and a HOMO–LUMO gap of 0.77 V.

Fig. 3.33

β,β-, meso,meso-, β’,β’-triply fused porphyrin dimers

Ag⁺-mediated meso-meso coupling of porphyrins and subsequent oxidative fusion leading to β,β-, meso,meso-, β’,β’-triply fused multiporphyrins 128 with DDQ-Sc(OTf)₃ were originally developed by Osuka’s group (Fig. 3.34) (Tsuda and Osuka 2001). Dimeric, trimeric, and tetrameric porphyrins show NIR absorption bands from 1100 to 1600 nm, and their 2PA cross section values (σ) were measured; 11,900 GM (λ_ex 1200 nm) for the dimer, 18,500 GM (λ_ex 2300 nm) for the trimer, and 41,200 GM (λ_ex 2300 nm) for the tetramer (Ahn et al. 2006; Nakamura et al. 2008).

Fig. 3.34

β,β-, meso,meso-, β’,β’-triply fused porphyrin dimers

As seen in many examples noted above, porphyrins show basic reaction behaviors characteristic of aromatic compounds, but unusual reaction behaviors were also observed probably due to macrocycle π-conjugation that stabilizes a radical state. Various organometallic transformations for modification of porphyrin structures have caused great developments in the porphyrin chemistry these days. It is well illustrated by the fact that photophysical and electrochemical properties can be fine-tuned to allow versatile applications as functional materials.