Synthesis of carbazoles by dehydro Diels-Alder reactions of ynamides

A new approach to carbazoles and benzannulated carbazoles by means of intramolecular dehydro Diels-Alder of ynamides is reported. N-(o-Ethynyl)aryl ynamides and N-(o-ethynyl) arylynamides were prepared in a few steps starting from o-iodoaniline. Thermal cycloaddition of N-(o-ethynyl)aryl ynamides and N-(o-ethynyl) arylynamides affords carbazoles and benzannulated and heteroannulated carbazoles in moderate-to-good yields.     

Recent topics in the desymmetrization of meso-diols

The desymmetrization of meso compounds is one of the most effective strategies for asymmetric synthesis. This digest focuses on recent progress in the desymmetrization of meso-diols and their derivatives. The topics discussed here include methods for the enzymatic acylation of meso-diols and the hydrolysis of meso-diesters, acylation, related reactions of meso-diols with organocatalysts and metal catalysts, the oxidation of meso-diols by enzymes, organocatalysts, and metal catalysts, and the desymmetrization of meso-dicarbamates with metal catalysts. The desymmetrization of meso-diols using tandem reactions is also discussed.     

Spectroscopic properties of meso-thienylporphyrins with different porphyrin cores

The absorption and fluorescence properties of a series of meso-thienylporphyrins with different porphyrin cores (N₄, N₃O, N₃S and N₂S₂ cores) were studied and compared with the corresponding meso-tetraarylporphyrins. The replacement of six-membered phenyl groups with five-membered thienyl groups at meso-positions resulted in red shifts and broadening of absorption and emission bands, low quantum yields and decreased S₁ state lifetimes and the maximum effects were observed for meso-tetrathienylporphyrin with N₂S₂ porphyrin core. Similar observations were noted for the dications of meso-thienylporphyrins compared to the dications of the corresponding meso-tetraarylporphyrins. These results suggest that the replacement of six-membered aryl group with five-membered thienyl groups at meso-positions, the electronic properties of the porphyrin were altered significantly.     

Synthesis and electronic properties of expanded 5-(hetero)aryl-thien-2-yl substituted 3-ethynyl quinoxalines with AIE characteristics

Expanded 5-(hetero)aryl-thien-2-yl substituted 3-ethynyl quinoxaline dyes with variable substitution pattern on the peripheral thiophene ring were synthesized in moderate to very good yields by Suzuki and Buchwald-Hartwig coupling of the corresponding brominated 3-ethynyl quinoxalines. Dumbbell-shaped bis(thienyl 3-ethynyl quinoxalines) are also accessible by the Suzuki protocol. The photophysical properties were investigated by UV and fluorescence spectroscopy. Most of the obtained compounds display fluorescence in solution and some of them also in the solid state. Additionally, tuning of the emission color of the quinoxaline based chromophores can be conveniently accomplished by the remote substituent group. The determined absorption and emission maximum as well as the Stokes shifts strongly correlate with Hammett σp+parameters. Besides,photophysical properties of selected derivatives in the solid state, biphasic solutions, and PMMA films, along with their relationships, are comparatively investigated. Moreover, two 5-(hetero)aryl-thien-2-yl substituted 3-ethynyl quinoxaline dyes are aggregation induced emission(AIE) chromophores indicated by restriction of molecular motions. A covalently restricted 3-ethynyl quinoxaline supports that the inhibition of molecular rotation is responsible for the significant enhancement of fluorescence in acetonitrile/water mixtures.     

Synthesis and spectral properties of N4, N3S, and N2S2 porphyrins containing one, two, three, and four meso-furyl groups

Porphyrins with N₄, N₃S, and N₂S₂ cores having one, two, three, and four furyl groups at the meso-positions were synthesized by following various methodologies and characterized by using mass spectrometry, NMR spectroscopy, elemental analysis, absorption, and fluorescence spectroscopic techniques. NMR studies indicated that by replacing the meso-aryl groups with meso-furyl groups, the β-pyrrole and β-thiophene protons of porphyrins experienced considerable downfield shifts, supporting the alteration of π-delocalization of porphyrins on the introduction of meso-furyl groups. The absorption and emission bands of porphyrins experienced red shifts on the introduction of meso-furyl groups and the magnitude of red shifts vary linearly with the number of meso-furyl groups. Thus, the spectral studies supported a systematic alteration in spectral properties on successive introduction of meso-furyl groups.     

meso-Tetraaryl-7,8-dihydroxydithiachlorins: first examples of heterochlorins

Osmium tetraoxide-mediated dihydroxylation of meso-tetraaryldithiaporphyrins generates the corresponding meso-tetraaryldithia-7,8-dihydroxychlorins and meso-tetraaryldithia-7,8,17,18-tetrahydroxybacteriochlorins. The products are spectroscopically characterized and the substitution positions were unequivocally determined. The UV-vis of the heterochlorins and heterobacteriochlorins are chlorin- and bacteriochlorin-like, respectively. However, the chlorin spectra are surprisingly hypsochromically shifted as compared to the corresponding all-aza chlorins, whereas the bacteriochlorin is bathochromically shifted. meso-Tetraaryldithia-7,8-dihydroxychlorins are susceptible to oxidative ring-opening reactions to form the corresponding meso-tetraaryldithia-7-oxo-8-oxa-dithiaporphyrin (dithiaporpholactone). These derivatives are the first examples of heterochlorins and β-modified dithiaporphyrins.     

meso-Dithiole and tetrathiafulvalene dipyrromethanes a route to metal dithiole-dipyrrin complexes and to fluorescent tetrathiafulvalene-BODIPY

A series of meso-dithiole and tetrathiafulvalene (TTF) dipyrromethanes have been prepared via the reaction of the appropriate aldehyde with either pyrrole or 3-ethyl-2,4-dimethyl-pyrrole under acid catalysis. Oxidation to the corresponding meso-dithiole dipyrrins is reported together with the formation of the metal chelate complexes (M=Zn, Cu, Ni) as well as the meso-dithiole boron-dipyrromethene (BODIPY). The molecular structures of these metal (Cu, Ni) and boron complexes are presented and discussed. According to a similar strategy the meso-TTF BODIPY is prepared and its photophysical properties are presented and compared with those of the meso-dithiole BODIPY.     

Synthesis of meso-furyl porphyrins with N4, N3S, N2S2 and N3O porphyrin cores

A series of meso-furyl porphyrins with four different porphyrin cores (N₄, N₃S, N₂S₂ and N₃O) were synthesized and characterized. The comparison of NMR, optical and fluorescence properties of meso-furyl porphyrins with porphyrins with six-membered aryl groups indicates that electronic properties of porphyrins were changed drastically on the introduction of furyl groups at meso positions. The maximum shifts in spectral bands were observed for meso-furyl porphyrins with N₂S₂ core. On protonation, the absorption bands of meso-furyl porphyrins were further red shifted. All these changes were ascribed to the possibility of more planarity of the meso-furyl porphyrins due to the small size of the furyl groups which results in extending the π-delocalisation of the porphyrin ring in to the furyl groups.     

Synthesis and fluorescence properties of covalently linked homo- and hetero-porphyrin dyads containing meso-tolyl porphyrin and meso-furyl porphyrin sub-units

Three porphyrin building blocks with N₄, N₃S and N₂S₂ cores having three meso-furyl groups and one meso-iodophenyl group were synthesized and characterized. The porphyrin building blocks were used to synthesize six porphyrin dyads such as N₄-N₄, N₃S-N₃S, N₂S₂-N₂S₂, N₄-N₃S, N₄-N₂S₂ and N₃S-N₂S₂ containing meso-tolyl and meso-furyl porphyrin sub-units under mild Pd(0) mediated coupling conditions. Steady state fluorescence studies indicated an efficient energy transfer from the meso-tolyl porphyrin sub-unit to the meso-furyl porphyrin sub-unit in all six dyads. This study supported the argument that the meso-furyl porphyrins can be used as good energy acceptors when meso-aryl porphyrins act as energy donors in their metal free form.     

Porphyrin N-Pincer Pd(II)-Complexes in Water: A Base-Free and Nature-Inspired Protocol for the Oxidative Self-Coupling of Potassium Aryltrifluoroborates in Open-Air

Metalloporphyrins (and porphyrins) are well known as pigments of life in nature, since representatives of this group include chlorophylls (Mg-porphyrins) and heme (Fe-porphyrins). Hence, the construction of chemistry based on these substances can be based on the imitation of biological systems. Inspired by nature, in this article we present the preparation of five different porphyrin, meso-tetraphenylporphyrin (TPP), meso-tetra(p-anisyl)porphyrin (TpAP), tetrasodium meso-tetra(p-sulfonatophenyl)porphyrin (TSTpSPP), meso-tetra(m-hydroxyphenyl)porphyrin (TmHPP), and meso-tetra(m-carboxyphenyl)porphyrin (TmCPP) as well as their N-pincer Pd(II)-complexes such as Pd(II)-meso-tetraphenylporphyrin (PdTPP), Pd(II)-meso-tetra(p-anisyl)porphyrin (PdTpAP), Pd(II)-tetrasodium meso-tetra(p-sulfonatophenyl)porphyrin (PdTSTpSPP), Pd(II)-meso-tetra(m-hydroxyphenyl)porphyrin (PdTmHPP), and Pd(II)-meso-tetra(m-carboxyphenyl)porphyrin (PdTmCPP). These porphyrin N-pincer Pd(II)-complexes were studied and found to be effective in the base-free self-coupling reactions of potassium aryltrifluoroborates (PATFBs) in water at ambient conditions. The catalysts and the products (symmetrical biaryls) were characterized using their spectral data. The high yields of the biaryls, the bio-mimicking conditions, good substrate feasibility, evading the use of base, easy preparation and handling of catalysts, and the application of aqueous media, all make this protocol very attractive from a sustainability and cost-effective standpoint.     

meso-Tetraaryl-7,8-diol-21,23-dithiachlorins and their pyrrole-modified derivatives: a spectroscopic comparison to their aza-analogues

Osmium tetraoxide-mediated dihydroxylation of meso-tetraaryl-21,23-dithiaporphyrins generates the corresponding meso-tetraaryl-7,8-dihydroxy-21,23-dithiachlorins and meso-tetraaryl-7,8,17,18-tetrahydroxy-21,23-dithiabacteriochlorins. Oxidative diol cleavage reactions of the meso-tetraaryldithia-7,8-dihydroxychlorin generate, depending on the conditions chosen, the corresponding meso-tetraaryldithia-7-oxa-8-oxo-21,23-dithiaporphyrin (dithiaporpholactone) or meso-tetraaryl-7,8-ethoxy-7a-oxa-7a-homo-21,23-dithiaporphyrin (morpholinodithiachlorin), respectively. The UV-vis spectra of the heterochlorins and pyrrole-modified dithiaporphyrins are compared to those of the corresponding all-aza homologues. In general, the trends which distinguish the spectra of dithiaporphyrins from those of all-azaporphyrins are preserved. Thus, the spectra of the dioldithiachlorins tetraoldithiabacteriochlorins are chlorin- and bacteriochlorin-like and bathochromically shifted as compared to the all-azaanalogues, respectively. Also, the dithiaporpholactone spectrum is porphyrin-like. However, the UV-vis spectrum of the morpholinodithiachlorin is uncharacteristic for a morpholinochlorin spectrum. The derivatives described are the first examples of heterochlorins and pyrrole-modified dithiaporphyrins.     

Synthesis and properties of BF2- & PO2-complexes of mono meso-heterocycle substituted 25-oxasmaragdyrins and derivatives

BF₂- and PO₂-smaragdyrins containing one five membered heterocycle such as pyrrole, thiophene and furan at one of the meso-position of corresponding 25-oxasmaragdyrins were synthesized by treating the appropriate mono meso-heterocycle substituted 25-oxasmaragdyrin with BF₃.OEt₂ and POCl₃ respectively in CH₂Cl₂ under mild reaction conditions. All macrocycles were thoroughly characterized by HR-MS and 1D and 2D NMR spectroscopy. The presence of a five membered heterocycle in place of a six membered aryl group significantly alters the electronic properties of the smaragdyrin macrocycle as reflected in their spectral and electrochemical properties. The meso-pyrrole BF₂-smaragdyrin was subjected to a Vilsmeier-Haack reaction to prepare meso-(α-formyl pyrrolyl) BF₂-smaragdyrin which was subsequently used to prepare meso-(α-dipyrromethanyl pyrrolyl) BF₂-smaragdyrin. The further use of meso-heterocycle substituted BF₂- and PO₂-oxasmaragdyrins was demonstrated by treating meso-pyrrolyl BF₂-smaragdyrin with pentafluorobenzaldehyde in CHCl₃ under mild acid catalysed conditions to afford an unusual dipyrromethanyl bridged BF₂-smaragdyrin dyad which exhibits excellent photophysical properties.     

Orientation of nucleophilic substitution in π-cation radicals or π-dications from meso-substituted metalloporphyrins

Treatment of meso-substituted metalloporphyrins [meso -substituent = OCOCF₃, OCOCH₃, OMe, CHO, CN, Cl; metal = Zn(II) or Cd(II)] with thallium(III) trifluoroacetate, followed by an acidic work-up, gives the corresponding β-substituted α-oxophlorins which were either characterised as such or else further derivatised. In all cases the major (or only) disubstitution product has the αβ orientation at the meso positions, indicating that the existing meso substituent directs the incoming one (trifluoroacetate) into the flanking, rather than opposite, meso position of the intermediate π-cation radical or π-dication. In contradistinction, meso substituted zinc(II) porphyrins which are able to lose protons (e.g. α-oxophlorins or α-aminoporphyrins) react with thallium(III) trifluoroacetate, and after a work-up with HCl the corresponding γ-chloro-α-oxophlorin or γ-chloro-α-aminoporphyrin is obtained.     

MS/MS Fragmentation Behavior Study of meso-Phenylporphyrinoids Containing Nonpyrrolic Heterocycles and meso-Thienyl-Substituted Porphyrins

Free base and cobalt(II) complexes of six meso-tetraphenylporphyrinoids containing nonpyrrolic heterocycles and of three meso-thienylporphyrins were investigated using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Their fragmentation was studied in a quadrupole ion trap as a function of the porphyrinoid macrocycle structure and compared with the fragmentation behavior of the benchmark compound meso-tetraphenylporphyrin. In situ oxidation of the neutral cobalt(II) complexes under ESI conditions produced singly charged cobalt(III) porphyrinoid ions; the free bases were ionized by protonation. For the porphyrinoids with an intact porphyrin core, the major fragmentation pathways observed were the losses of the meso-substituent (for meso-phenyl groups) and characteristic fragmentations of one or more meso-substituents (for the meso-thienyl group). Complex fragmentation pathways were observed for porphyrinoids with modifications to the porphyrin core but chemically reasonable structures could be assigned to most fragments, thus delineating general patterns for the behavior of pyrrole-modified porphyrins under CID conditions.

Palladium-catalyzed meso-amination and amidation of porphyrins: marked acceleration with the Ni(II) central metal ion

The preparation of meso-amino and meso-amido substituted porphyrins was easily accomplished by palladium-mediated cross-coupling reactions of meso-brominated porphyrins with amines and amides. Ni(II) introduced as a central metal ion into the substrate porphyrin markedly accelerated the cross-coupling.     

The meso-β-linkage as structural motif in porphyrin-based donor-acceptor compounds

Synthetic strategies for using the meso-β-linkage as a structural motif in electron transfer mimics have been tested. Exploratory syntheses of directly meso-β-linked bis- and trisporphyrins and the first representative X-ray structure of a meso-β-linked bisporphyrins are reported. The structure reveals a unique form of intramolecular π-π stabilization between one porphyrin and a meso-aryl substituent in a second porphyrin unit that accounts for the stability of different atropisomers in trimers. Using β-formyl porphyrins, dipyrromethanes, and suitable quinone precursor aldehydes, mixed condensations gave convenient access to porphyrin-porphyrin-quinone (P-P-Q) donor-acceptor systems consisting of a meso-β-linked bisporphyrin, a spacer, and a quinone acceptor.     

Synthesis of flexible dimeric meso-tetrakis-porphyrins

Monofunctionalisation of meso-tetrakis-porphyrins through introduction of a carboxylic group in the meso position of the phenyl group confers the necessary characteristics to anchor them through stable amide bonds to functionalised supports or to molecules. In this Letter we describe the synthesis, characterisation and photophysical evaluation of such a functionalised flexible dimeric porphyrin, bis-(meso-tetrakis-5,10,15-triphenyl-20-(p-carboxyphenyl)-porphyrinyl)-1,6-hexanediamide.     

Synthesis and studies of covalently linked meso-furyl boron-dipyrromethene-ferrocene conjugates

Four meso-furyl BODIPY-ferrocene conjugates 1–4 in which one or more ferrocene groups were connected directly to BODIPY core or meso-furyl group were synthesized by coupling of appropriate bromo meso-furyl BODIPYs with α-ethynylferrocene under mild Pd(0) coupling conditions. The compounds were characterized by HR-MS mass, NMR, absorption, electrochemistry and fluorescence techniques. The absorption studies of compounds 1–4 showed charge transfer band in addition to BODIPY absorption bands indicating that the BODIPY and ferrocene moieties interact within the conjugates. On the other hand, the charge transfer band is absent in meso-phenyl BODIPY-ferrocene conjugate due to the orthogonal arrangement of ferrocene appended meso-phenyl group with BODIPY core which prevents the interaction between the two moieties. The electrochemical studies showed strong oxidation due to ferrocene moiety and reduction due to meso-furyl BODIPY unit. The compounds 3 and 4 which contain two and three ferrocenyl groups respectively were oxidized at the same potential with two and three electrons involved in the redox process. The compounds 1–4 are weakly fluorescent due to electron transfer from ferrocene unit to BODIPY unit. However, the fluorescence can be restored by oxidizing the ferrocene to ferrocenium ion which prevents the electron transfer between the two moieties. The computational studies support the experimental results.     

Structural parameters and vibrational spectra of a series of zinc meso-phenylporphyrins: A DFT and experimental study

The influences of meso-phenyl substitution on the geometric structure and vibrational spectra have been studied by DFT calculation (B3LYP/6-31G(d)) and experiment on a series of zinc porphyrins (ZnTPP: zinc 5,10,15,20-tetraphenylporphyrin; ZnTrPP: zinc 5,10,15-triphenylporphryin; ZnDPP: zinc 5,15-dipenylporphyirn; ZnMPP: zinc 5-monophenylporphyrin; ZnP: zinc porphine). Calculation indicates that meso-phenyl substitution gives rise to slight out-of-plane distortion but significant in-plane distortion, especially for the configuration around C_m atom, to zinc porphyrin. The assignment of experimental vibrational spectra was proposed mainly on the basis of calculation. Different shifting tendency upon meso-phenyl substitution is observed for different structure-sensitive bands, such as the shifting of ν₂, ν₃, ν₆, and ν₈ modes toward higher frequencies and ν₄ and ν₂₈ modes toward lower frequencies, upon meso-phenyl substitution. This is attributed primarily to in-plane nuclear reorganization effect (IPNR), though the contribution from out-of-plane distortion cannot be excluded completely. Analysis on vibrational structure reveals that asymmetric meso-phenyl substitution, especially the 5,15-diphenyl substitution of ZnDPP, brings about asymmetric vibrational displacement, or even splitting of vibrational structure to normal modes involving mainly the motion of meso-C_m. This is ascribed to the reduction of symmetry of porphyrin skeleton caused by asymmetric meso-phenyl substitution.     

Synthesis of Conformationally Constrained d-Glu-meso-DAP Analogs as Innate Immune Agonists

The dipeptide d-Glu-meso-DAP (iE-DAP) is the minimal structural fragment capable of activating the innate immune receptor nucleotide-binding oligomerization domain protein (NOD1). The meso-diaminopimelic acid (meso-DAP) moiety is known to be very stringent in terms of the allowed structural modifications which still retain the NOD1 activity. The aim of our study was to further explore the chemical space around the meso-DAP portion and provide a deeper understanding of the structural features required for NOD1 agonism. In order to achieve the rigidization of the terminal amine functionality of meso-DAP, isoxazoline and pyridine heterocycles were introduced into its side-chain. Further, we incorporated the obtained meso-DAP mimetics into the structure of iE-DAP. Collectively, nine innovative iE-DAP derivatives additionally equipped with lauroyl or didodecyl moieties at the α-amino group of d-Glu have been prepared and examined for their NOD1 activating capacity. Overall, the results obtained indicate that constraining the terminal amino group of meso-DAP abrogates the compounds’ ability to activate NOD1, since only compound 6b retained noteworthy NOD1 agonistic activity, and underpin the stringent nature of this amino acid with regard to the allowed structural modifications.