Origin of the Regioselective Reduction of Chlorins

The reduction of a free-base chlorin generally forms a bacteriochlorin (BC), while the reduction of the corresponding metallochlorin forms a metalloisobacteriochlorin (M-iBC). This regioselectivity has been long known but was never fully rationalized. In the free-base case, this regioselectivity can be explained using resonance arguments, but the explanations for the regioselectivity in the metallochlorin reactions requires a more sophisticated approach. A combination of DFT-calculated average local ionization energies (ALIEs), thermodynamics of the products, and the transition-state trajectories of reduction reactions of <i>meso</i>-tetraaryl- and β-octaethylchlorins, as their free bases and zinc complexes, now fully delineate the theoretical basis of the reduction regioselectivity. The reactions are kinetically controlled. Steric effects originating in the conformational flexibility of the chlorin macrocycle direct the reactions toward the formation of iBCs. Only when electronic effects are strong enough to override the steric effects are BCs formed. Depending on the substituents present on the chlorin, this regioselectivity may change, but ALIE calculations provide reliable guidelines to predict this. The practical value of this work lies in the presentation of a simple predictive method toward synthetic tetrahydroporphyrins by reduction of chlorins

<i>meso</i>-Tetrakis(pentafluorophenyl)porphyrin-Derived Chromene-Annulated Chlorins

The synthesis of mono- and bis-chromene-annulated <i>meso</i>-(pentafluorophenyl)­chlorins from <i>meso</i>-tetrakis­(pentafluorophenyl)­porphyrins by an OsO₄-mediated dihydroxylation reaction, followed by an intramolecular nucleophilic aromatic substitution reaction, is described. The reaction sequence is applicable to the free base systems as well as their Zn­(II), Ni­(II), Pd­(II), and Pt­(II) complexes. The optical properties (UV–vis and fluorescence spectra) of the (metallo)­chlorin-like chromophores that possess slightly red-shifted optical spectra compared to the corresponding 2,3-dihydroxychlorins are reported. Molecular modeling and ¹H–¹⁹F-HOESY NMR spectroscopy provide indications for the conformation of the chromene-annulated chromophores. Using ¹H–¹H COSY and ¹⁹F–¹⁹F QF-COSY NMR spectra, we interpret the ¹H and ¹⁹F NMR spectra of the porphyrins and chlorins, thus providing a refined reference point for the use of ¹⁹F NMR spectroscopy as a diagnostic tool in the analysis of <i>meso</i>-pentafluorophenyl-substituted porphyrinoids

Reaching across the Divide: How Monometalation of One Binding Pocket Affects the Empty Binding Pocket in a Siamese-Twin Porphyrin Palladium Complex

Siamese-twin porphyrin is a pyrazole-containing expanded porphyrin incorporating two porphyrin-like binding pockets. The macrocycle, however, does not possess an aromatic π system but rather two separated conjugation pathways that are isolated by the pyrazole junctions. Mono- and bimetallic complexes of the Siamese-twin porphyrin are known. This work addresses in detail the electronic consequences that monometalation (with Pd^II) has on the electronic properties of the nonmetalated binding pocket by studying the solid-state structure, acid/base, and electrochemical properties of the monopalladium twin-porphyrin complex. Specifically, metalation leads to a switch of the protonation sites of the free-base pocket. The unusual location of the protons at adjacent pyrrolic nitrogen atoms was revealed using X-ray diffraction and 1D/2D NMR spectroscopy. The one-electron oxidation and reduction events are both ligand-centered, as derived by spectroelectrochemical and electron paramagnetic resonance measurements, but are located on different halves of the molecule. Single-electron oxidation (−0.32 V vs Fc/Fc⁺) generated an organic radical centered on the metal-coordinating side of the ligand, while single-electron reduction (−1.59 V vs Fc/Fc⁺) led to the formation of an organic radical on the free-base side of the macrocycle. Density functional theory calculations corroborated the redox chemistry observed. The possibility of selectively preparing the monometallic complexes carrying two distinct redox sitesa metal-containing oxidation site and a metal-free reduction sitefurther expands the potential of Siamese-twin porphyrins to serve as an adjustable platform for multielectron redox processes in chemical catalysis or molecular electronics applications

Mono- and Bisquinoline-Annulated Porphyrins from Porphyrin β,β′‑Dione Oximes

An acid-induced reaction of <i>meso</i>-tetraphenyl-2-hydroxyimino-3-oxoporphyrin leads, with concomitant loss of water, to a formal electrophilic aromatic substitution of the ortho-position of the phenyl group adjacent to the oxime, forming a quinoline moiety. Owing in part to the presence of a π-extended chromophore, the resulting <i>meso</i>-triphenylmonoquinoline-annulated porphyrin (λ_max = 750 nm) possesses a much altered optical spectrum from that of the starting oxime (λ_max = 667 nm). An oxidative DDQ-induced ring-closure process is also possible, generating the corresponding <i>meso</i>-triphenylmonoquinoline-annulated porphyrin quinoline <i>N</i>-oxide, possessing a slightly shifted and sharpened UV–vis spectrum (λ_max = 737 nm). The connectivity of the chromophores was conclusively shown by NMR spectroscopy. Both ketone functionalities in <i>meso</i>-tetraphenyl-2,3-dioxoporphyrin can be converted, via the oxime and using the acid- or oxidant-induced reaction pathways, either in one step or in a stepwise fashion, to bisquinoline-annulated porphyrin (λ_max = 775 nm) and its <i>N</i>-oxide (λ_max = 779 nm), respectively. This process is complementary to a previously established pathway toward bisquinoline-annulated porphyrins. Their zinc­(II), nickel­(II), and palladium­(II) complexes are also described. Several examples of the quinoline-annulated porphyrins were crystallographically characterized, proving their connectivity and showing their conformations that are extremely distorted from planarity. The work presents a full account on the synthesis, structure, and spectroscopic properties of these classes of NIR-absorbing dyes

Fusion and Desulfurization Reactions of Thiomorpholinochlorins

An unusually nonplanar, ruffled structure that had been suspected for the previously reported [2,3-bismethylene­thio­morpholino­chlorinato]­nickel­(II) complex was confirmed by determination of its crystal structure. Treatment of this thiomorpholinochlorin with acid converts the exocyclic double bonds to direct links to the <i>ortho</i>-positions of both adjacent <i>meso</i>-phenyl groups. The crystal structure of this product indicated that the introduction of these linkages did not change the overall conformation of the macrocycle. The reactivity of the bis-linked thiomorpholine moiety with respect to Raney-nickel-induced (hydro)­desulfurization reactions was probed, forming a bis-phenyl-linked 2,3-dimethylchlorin, also characterized by X-ray diffraction, and a bis-indene-annulated porphyrin. We also report on the synthesis of the oxygen analogue to the bis-linked thiomorpholine by reaction of a secochlorin bisketone nickel complex with Woollins’ reagent. We thus introduce novel methodologies toward the synthesis of porphyrinoids carrying β-to-<i>ortho</i>-phenyl fusions and expand on the scope and limits of the chemistry and interconversion of pyrrole-modified porphyrins

Reaching across the Divide: How Monometalation of One Binding Pocket Affects the Empty Binding Pocket in a Siamese-Twin Porphyrin Palladium Complex

Siamese-twin porphyrin is a pyrazole-containing expanded porphyrin incorporating two porphyrin-like binding pockets. The macrocycle, however, does not possess an aromatic π system but rather two separated conjugation pathways that are isolated by the pyrazole junctions. Mono- and bimetallic complexes of the Siamese-twin porphyrin are known. This work addresses in detail the electronic consequences that monometalation (with Pd^II) has on the electronic properties of the nonmetalated binding pocket by studying the solid-state structure, acid/base, and electrochemical properties of the monopalladium twin-porphyrin complex. Specifically, metalation leads to a switch of the protonation sites of the free-base pocket. The unusual location of the protons at adjacent pyrrolic nitrogen atoms was revealed using X-ray diffraction and 1D/2D NMR spectroscopy. The one-electron oxidation and reduction events are both ligand-centered, as derived by spectroelectrochemical and electron paramagnetic resonance measurements, but are located on different halves of the molecule. Single-electron oxidation (−0.32 V vs Fc/Fc⁺) generated an organic radical centered on the metal-coordinating side of the ligand, while single-electron reduction (−1.59 V vs Fc/Fc⁺) led to the formation of an organic radical on the free-base side of the macrocycle. Density functional theory calculations corroborated the redox chemistry observed. The possibility of selectively preparing the monometallic complexes carrying two distinct redox sitesa metal-containing oxidation site and a metal-free reduction sitefurther expands the potential of Siamese-twin porphyrins to serve as an adjustable platform for multielectron redox processes in chemical catalysis or molecular electronics applications

Octaethyl-1,3-oxazinochlorin: A β‑Octaethylchlorin Analogue Made by Pyrrole Expansion

Treatment of the oxime of octaethyloxochlorin <b>4</b>, available from octaethylporphyrin <b>3</b>, under Beckmann conditions provided not the expected lactam, but octaethyl-1,3-oxazinochlorin <b>8</b>, in which a pyrrole moiety of the parent oxochlorin was expanded by an oxygen atom to an 1,3-oxazinone moiety. Its mechanism of formation was demonstrated to occur along an “abnormal Beckmann” pathway, followed by intramolecular ring closure and hydrolysis. The work expands the methodologies known to convert octaethylporphyrin to pyrrole-modified porphyrin analogues

Fusion and Desulfurization Reactions of Thiomorpholinochlorins

An unusually nonplanar, ruffled structure that had been suspected for the previously reported [2,3-bismethylene­thio­morpholino­chlorinato]­nickel­(II) complex was confirmed by determination of its crystal structure. Treatment of this thiomorpholinochlorin with acid converts the exocyclic double bonds to direct links to the <i>ortho</i>-positions of both adjacent <i>meso</i>-phenyl groups. The crystal structure of this product indicated that the introduction of these linkages did not change the overall conformation of the macrocycle. The reactivity of the bis-linked thiomorpholine moiety with respect to Raney-nickel-induced (hydro)­desulfurization reactions was probed, forming a bis-phenyl-linked 2,3-dimethylchlorin, also characterized by X-ray diffraction, and a bis-indene-annulated porphyrin. We also report on the synthesis of the oxygen analogue to the bis-linked thiomorpholine by reaction of a secochlorin bisketone nickel complex with Woollins’ reagent. We thus introduce novel methodologies toward the synthesis of porphyrinoids carrying β-to-<i>ortho</i>-phenyl fusions and expand on the scope and limits of the chemistry and interconversion of pyrrole-modified porphyrins

[3 + 2]-Cycloadditions with Porphyrin β,β′-Bonds: Theoretical Basis of the Counterintuitive <i>meso</i>-Aryl Group Influence on the Rates of Reaction

Removal of a β,β′-bond from meso-tetraarylporphyrin using [3 + 2]-cycloadditions generates meso-tetraarylhydroporphyrins. Literature evidence indicates that meso-tetraphenylporphyrins react more sluggishly with 1,3-dipoles such as ylides and OsO4 (in the presence of pyridine) than meso-tetrakis(pentafluorophenyl)porphyrin. The trend is counterintuitive for the reaction with OsO4, as this formal oxidation reaction is expected to proceed more readily with more electron-rich substrates. This work presents a density functional theory–based computational study of the frontier molecular orbital (FMO) interactions and reaction profile thermodynamics involved in the reaction of archetypical cycloaddition reactions (a simple ylide, OsO4, OsO4·py, OsO4·(py)2, and ozone) with the β,β′-double bonds of variously fluorinated meso-arylporphyrins. The trend observed for the Type I cycloaddition of an ylide is straightforward, as lowering the LUMO of the porphyrin with increasing meso-phenyl-fluorination also lowers the reaction barrier. The corresponding simple FMO analyses of Type III cycloadditions do not correctly model the reaction energetics. This is because increasing fluorination leads to lowering of the porphyrin HOMO–2, thus increasing the reaction barrier. However, coordination of pyridine to OsO4 preorganizes the transition state complex; lowering of the energy barrier by the preorganization exceeds the increase in repulsive orbital interactions, overall accelerating the cycloaddition and rationalizing the counterintuitive experimental findings

Oxazolochlorins. 9. <i>meso</i>-Tetraphenyl-2-oxabacteriochlorins and <i>meso</i>-Tetraphenyl-2,12/13-dioxabacteriochlorins

The formal replacement of one or two pyrrole groups in <i>meso</i>-tetraphenylporphyrin by oxazole moieties is described, generating inter alia the bacteriochlorin-type chromophores oxazolobacteriochlorins (oxabacteriochlorins) and bisoxazolobacteriochlorins (dioxabacteriochlorins). The key step is the conversion of a β,β′-dihydroxy-functionalized pyrroline group into an oxazolone or (substituted) oxazole. Depending on the substitution pattern on the oxazole or oxazoline moieties, mono- and dioxabacteriochlorins may have chlorin- or bacteriochlorin-like spectra. The optical properties (as measured by UV–vis and fluorescence spectroscopies) of the novel oxa- and dioxabacteriochlorins are described and contrasted against benchmark chlorins and bacteriochlorins. The conformations of a representative number of mono- and dioxabacteriochlorins, as their free bases or Zn^II complexes, were determined by single-crystal X-ray diffractometry. They proved to be essentially planar, showing that the modulation of their optical properties is primarily due to their intrinsic electronic structures and electronic substituent effects and are not largely affected by conformational effects. The mono- and bisoxazolobacteriochlorins are a novel class of readily prepared and oxidatively stable chlorin and bacteriochlorin analogues with tunable optical spectra that, in part, reach into the NIR