The reaction of porphyrins with organolithium reagents

Porphyrins react readily with organolithium reagents, preferentially in the meso positions. The overall reaction is a nucleophilic substitution and proceeds via initial reaction of the organic nucleophile with a meso carbon yielding an anionic species which is hydrolyzed to a porphodimethene (5,15-dihydroporphyrin), formally constituting an addition reaction to two Cm positions. Subsequent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) yields meso-substituted porphyrins. The reaction is highly versatile as it is accomplished in high, often quantitative yields with various alkyl or aryl lithium reagents. In addition, LiR can be used for reaction with a variety of metal complexes (best with NiII, but also with ZnII, CuII, and CoII) and most useful with free base porphyrins. Similarly beneficial this reaction can be used in sequence for the introduction of 1, 2, 3, or 4 (different) meso substituents giving for the first time an entry into any desired meso-substituted porphyrin. If meso-substituted porphyrins are used, reaction with LiR can be used for either the preparation of phlorins (already known reaction), porphodimethenes (5,15-dihydroporphyrins, including those with exocyclic double bonds, for example, 5(1),5(2)-didehydroporphyrins) or chlorins (2,3-dihydroporphyrins) depending on the substituent type in the reactant porphyrins. Thus, this reaction presents a generally applicable method for the facile and versatile functionalization of porphyrins.     

Synthesis of N-confused phlorins via an addition/cyclization pathway

The syntheses of N-confused phlorins are provided by reactions of N-confused porphyrins with nitrilimines and with dialkyl acetylenedicarboxylate. Both reactions involve zwitterionic intermediates and proceed through an addition/cyclization pathway.     

Asymmetric Multicomponent Reactions Based on Trapping of Active Intermediates

Metal carbenes derived from transition metal‐catalyzed decomposition of diazo compounds react with nucleophiles with heteroatoms, such as alcohols and amines, to generate highly active oxonium/ammonium ylides intermediates. These intermediates can be trapped by appropriate electrophiles to provide three‐component products. Based on this novel trapping process, we have developed novel multicomponent reactions (MCRs) of diazo compounds, alcohols/anilines, and electrophiles. The nucleophiles were also extended to electron‐rich heterocycles (indoles and pyrroles)/arenes, in which the resulting zwitterionic intermediates were also trapped by electrophiles. By employing efficient catalysis strategy, the reactions were realized with excellent stereocontrol and wide substrate scope. In this personal account, we introduce our breakthroughs in the development of novel asymmetric MCRs via trapping of the active ylides and zwitterionic intermediates with a number of electrophiles, such as imines, aldehyde, and Michael acceptors, under asymmetric catalysis. Transition metal/chiral Lewis acid catalysis, transition metal/Brønsted acid catalysis, and chiral transition‐metal catalysis, enable excellent stereocontrolled outcomes. The methodologies not only provide experimental evidence to support the existence of protic onium ylides intermediates/zwitterionic intermediates and the stepwise pathways of carbene‐induced O?H, N?H and C?H insertions, but also offer a novel approach for the efficient construction of chiral polyfunctional molecules.     

Forming Tertiary Organolithiums and Organocuprates from Nitrile Precursors and their Bimolecular Reactions with Carbon Electrophiles to Form Quaternary Carbon Stereocenters

Unstabilized tertiary organolithium intermediates are conveniently generated by reductive decyanation of nitriles, and these reagents and their derived cuprates couple in useful yields with carbon- centered electrophiles (see example). Chiral tertiary organolithium and organocuprate derivatives of substituted cis-perhydroazulenes and cis-perhydropentalenes react with electrophiles with high diastereoselectivity from the more-hindered concave face.     

Lithiation of 3-(Acylamino)-2-unsubstituted-, 3-(Acylamino)-2-ethyl-, and 3-(Acylamino)-2-propyl-4(3H)-quinazolinones: Convenient Syntheses of More Complex Quinazolinones(1)

3-(Pivaloylamino)- and 3-(acetylamino)-4(3H)-quinazolinones react with alkyllithium reagents to give 1,2-addition products in very good yields. Lithiation takes place with LDA and is regioselective at position 2. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding substituted derivatives in very good yields. Reactions of the lithium reagents with iodine give oxidatively dimerized cyclic structures. 3-(Pivaloylamino)- and 3-(acetylamino)-2-ethyl-4(3H)-quinazolinones and 3-(pivaloylamino)- and 3-(acetylamino)-2-propyl-4(3H)-quinazolinones are lithiated at the benzylic position with LDA. The lithium reagents so produced also react with a variety of electrophiles to give the corresponding 2-substituted-4(3H)-quinazolinone derivatives in very good yields. However, lithiation of 3-(acylamino)-2-(1-methylethyl)-4(3H)-quinazolinones was unsuccessful, as were lithiations of compounds having a diacetylamino group at position 3. The amide groups have been cleaved in good yield under basic or acidic conditions from some of the products to provide access to the free amino compounds.     

Synthesis, characterization and spectral properties of substituted tetraphenylporphyrin iron chloride complexes

A series of substituted tetraphenylporphyrin iron chloride complexes [RTPPFe(III)Cl, R=o/p-NO?, o/p-Cl, H, o/p-CH?, o/p-OCH?] were synthesized by a novel universal mixed-solvent method and the spectral properties of free base porphyrins and iron porphyrin compounds were compared with each other. The experimental results showed that the one-pot mixed solvent method was superior to the two-step method in the yields, reaction time and workup of reaction mixtures for the synthesis of iron porphyrin compounds. The highest yields (28.7%-40.4%) of RTPPFe(III)Cl were obtained in the mixed solvents propionic acid, glacial acetic acid and m-nitrotoluene under reflux for 2 h. A detailed analysis of ultraviolet-visible (UV-vis), infrared (IR) and far-infrared (FIR) spectra suggested the transformation from free base porphyrins to iron porphyrins. The red shift of the Soret band in ultraviolet-visible spectra due to the presence of p-nitrophenyl substituents and the blue shift of Fe-Cl bond of TPPFeCl in far-infrared spectra were further explained by the electron transfer and molecular planarity in the porphyrin ring.     

Influence of cations on zinc(II) incorporation into crown porphyrins

The decrease in rate constants of Zn(II) incorporation into fully and partially benzo-15-crown-5 meso substituted porphyrins in the presence of cations has been explained on the basis of cation complexation ability of the crown ether cavities rather than steric effects.     

Conformational landscape of meso-(1,3-dithian-2-yl)porphyrins

An investigation of the conformational landscape of 1,3-dithian-2-yl bearing porphyrins and the rotational behavior of the dithianyl substituents in meso position was carried out by variable-temperature (VT) NMR spectroscopy. Additionally, theoretical results for alternative conformations and energy barriers were obtained by molecular modeling. The study revealed different NH trans tautomers with regard to the orientation of the dithianyl ligands for the free base porphyrins 1-3. Relatively ruffled porphyrin core conformations were established for the transition states of the dithianyl rotation, resulting in a lower rotational energy barrier for the nickel(II) complex 4 compared to that of the free base systems. The data obtained and the first depiction of a rotational transition state for the rotation of bulky meso-alkyl substituents illustrate the close structural interplay between meso-alkyl substituents and the macrocycle conformation in porphyrins.     

Metal-molecule interactions upon deposition of copper overlayers on reactively functionalized porphyrin monolayers on Si(100)

The interaction of evaporated Cu deposited on a series of porphyrins in monolayers covalently attached to Si(100) substrates was investigated using cyclic voltammetry and FTIR spectroscopy. Each porphyrin contains a triallyl tripod attached to the porphyrin via a p-phenylene unit. The tripod anchors the porphyrin to the Si(100) substrate via hydrosilylation of the allyl groups. Two of the porphyrins are Zn chelates that possess meso p-cyanophenyl substituentsone, ZnP-CND, contains a single group opposite (distal) to the tripodal surface anchor, whereas the other, ZnP-CNL, contains two groups orthogonal (lateral) to the surface anchor. A third Zn porphyrin, ZnP, containing nonreactive p-tolyl groups at all three nonanchoring meso positions, was examined for comparison. The fourth porphyrin, FbP-HD, is a metal-free species (free base) that contains nonreactive phenyl (distal) and p-tolyl groups (lateral) at the three nonanchoring meso positions. The fifth porphyrin, CuP-HD, is the Cu chelate of FbP-HD, and serves as a reference complex for evaluating the effects of Cu metal deposition onto FbP-HD. The studies indicate that all of the porphyrin monolayers are robust under the conditions of Cu deposition, experiencing no noticeable degradation. In addition, the Cu metal does not penetrate through the monolayer to form electrically conductive filaments. For the ZnP-CND monolayers, the deposited Cu quantitatively reacts/complexes with the distal cyano group. In contrast, for the ZnP-CNL monolayers no reaction/complexation of the lateral cyano groups is observed. For the FbP-HD monolayers, Cu deposition results in quantitative insertion of Cu into the free base porphyrin. Collectively, the studies demonstrate that porphyrin monolayers are amenable to direct deposition of Cu overlayers and that functionalization of the porphyrins can be used to mediate the attributes of the metal-molecule junction.     

Three Short Stories about Hexaarylbenzene–Porphyrin Scaffolds

A feasible two‐step synthesis and characterization of a full series of hexaarylbenzene (HAB) substituted porphyrins and tetrabenzoporphyrins is presented. Key steps represent the microwave‐assisted porphyrin condensation and the statistical Diels–Alder reaction to the desired HAB‐porphyrins. Regarding their applications, they proved to be easily accessible and effective high molecular mass calibrants for (MA)LDI mass spectrometry. The free‐base and zinc(II) porphyrin systems, as well as the respective tetrabenzoporphyrins, demonstrate in solid state experiments strong red‐ and near‐infrared‐light emission and are potentially interesting for the application in “truly organic” light‐emitting devices. Lastly, they represent facile precursors to large polycyclic aromatic hydrocarbon (PAH) substituted porphyrins. We prepared the first tetra‐hexa‐peri‐hexabenzocoronene substituted porphyrin, which represents the largest prepared PAH‐porphyrin conjugate to date.     

Synthesis, spectroscopic properties, and tautomerism of mono-meso-substituted octamethylporphyrins

The synthesis spectroscopic properties and tautomerism of four novel mono-meso substituted(R)-octamethylporphyrins (R=o-hydroxybenzyl, p-aminobenzyl, 4-pyridinyl, and ferro-cenyl) were investigated. It was found that the porphyrins 2, 3 could be directly prepared in good yields via the coupling reaction of salicylaldehyde and p-aminobenzyl aldehyde with octamethyl-l',8'-dideoxy-ac-biladiene dihydrobromide, respectively. The free energy of activation (G) of the tautomerism of the porphyrins was calculated and interpreted in terms of electronic and steric nature. In contrast with 2-substituted-5,10,15,20-tetraphenylporphyrins, the substituents in meso position do not change the relative amount of two tautomers a and 6.     

Porphyrins fused with unactivated polycyclic aromatic hydrocarbons

A systematic study of the preparation of porphyrins with extended conjugation by meso,β-fusion with polycyclic aromatic hydrocarbons (PAHs) is reported. The meso-positions of 5,15-unsubstituted porphyrins were readily functionalized with PAHs. Ring fusion using standard Scholl reaction conditions (FeCl(3), dichloromethane) occurs for perylene-substituted porphyrins to give a porphyrin β,meso annulated with perylene rings (0.7:1 ratio of syn and anti isomers). The naphthalene, pyrene, and coronene derivatives do not react under Scholl conditions but are fused using thermal cyclodehydrogenation at high temperatures, giving mixtures of syn and anti isomers of the meso,β-fused porphyrins. For pyrenyl-substituted porphyrins, a thermal method gives synthetically acceptable yields (>30%). Absorption spectra of the fused porphyrins undergo a progressive bathochromic shift in a series of naphthyl (λ(max) = 730 nm), coronenyl (λ(max) = 780 nm), pyrenyl (λ(max) = 815 nm), and perylenyl (λ(max) = 900 nm) annulated porphyrins. Despite being conjugated with unsubstituted fused PAHs, the β,meso-fused porphyrins are more soluble and processable than the parent nonfused precursors. Pyrenyl-fused porphyrins exhibit strong fluorescence in the near-infrared (NIR) spectral region, with a progressive improvement in luminescent efficiency (up to 13% with λ(max) = 829 nm) with increasing degree of fusion. Fused pyrenyl-porphyrins have been used as broadband absorption donor materials in photovoltaic cells, leading to devices that show comparatively high photovoltaic efficiencies.     

Interactions of cationic porphyrins with double-stranded oligodeoxynucleotides: a study by electrospray ionisation mass spectrometry

Electrospray ionisation mass spectrometry (ESI-MS), electrospray ionisation tandem mass spectrometry (ESI-MS/MS) and Ultraviolet-visible (UV-vis) spectroscopy were used to investigate the non-covalent interactions between small oligonucleotide duplexes with the GC motif and a group of cationic meso(N-methylpyridynium-4-yl)porphyrins (four free bases with one to four positive charges, and the zinc complex of the tetracationic free base).The results obtained point to outside binding of the porphyrins, with the binding strength increasing with the number of positive charges. Fragmentations involving losses from both chains were observed for the porphyrins with N-methylpyridinium-4-yl groups in opposite meso positions.     

Selective functionalisatlon: Part 10. The nitration of phenols by pyridine derivatives carrying a transferable nitro group

Pyridinium salts bearing carboxylate side chains and pyridones are shown to react with nitronium tetrafluoroborate or nitrogen dioxide to yield activated intermediates capable of selectively nitrating phenol ortho to the hydroxyl group with virtually complete selectivity and in quantitative yield in aprotic solvents. Although the nitration of phenol itself is exceptionally selective, the nitration of some substituted phenols lead to mixtures of mononitrated products and in especially reactive cases such as 4-methoxyphenol and naphthols, to dinitrated products also. The reactions can be most conveniently carried out on a polymeric support. Spectroscopic evidence is presented to show that intermolecular association between pyridinium salts and the phenols takes place under conditions similar to the reaction conditions and that hydrogen bonding between the phenolic hydroxyl group and acceptor groups on the pyridine ring can also occur. It is suggested that the combination of these two effects leads to the observed selectivity. Attempts to extend the scope of the reaction to other electrophiles and substrates are outlined.     

Acetoxy Meldrum's acid: a versatile acyl anion equivalent in the Pd-catalyzed asymmetric allylic alkylation

Acetoxy Meldrum's acid can serve as a versatile acyl anion equivalent in the Pd-catalyzed asymmetric allylic alkylation. The reaction of this nucleophile with various meso and racemic electrophiles afforded alkylated products in high yields and enantiopurities. These enantioenriched products are versatile intermediates that can be further functionalized using nitrogen- and oxygen-centered nucleophiles, affording versatile scaffolds for the synthesis of nucleoside analogues. These scaffolds were used to complete formal syntheses of the anti-HIV drugs carbovir, abacavir, and the antibiotic aristeromycin.     

水溶性卟啉催化氧化1,5-萘二酚

合成并表征了系列水溶性卟啉配体[H2TPPS: 5,10,15,20-四-(4-磺酸基苯基)-21H,23H-卟啉, H2TMPyP: 5,10,15,20-四(4-吡啶基)-21H,23H-卟啉, H2TCPP: 5,10,15,20-四-(4-羧基苯基)-21H,23H-卟啉]及相应的铁、锌及钴配合物. 将水溶性卟啉作为光敏剂, 用于1,5-萘二酚的光催化反应, 产物为5-羟基-1,4萘醌. 利用UV-Vis方法对卟啉催化1,5-萘二酚的反应过程进行了监测, 探索了水相和水/二氯甲烷双相催化体系, 确定了较为理想的反应条件. 探讨了不同取代基和不同金属离子对卟啉催化性能的影响, 初步讨论了催化机理. 结果表明, 具有磺酸根阴离子取代基的水溶性卟啉具有最好的催化活性; 卟啉的催化活性与其在反应体系中的稳定性密切相关; 铁卟啉在反应初期呈现很高的催化活性, 但在光照条件下容易发生光解而导致催化活性的降低; 无金属的磺酸卟啉在催化体系中的催化活性和稳定性最好.     

Reactions of Dimethyl Heteroaroylphosphonates with Trialkyl Phosphite in the Presence of Proton Donors

Abstract

We have previously shown that substituted bcnzoylphosphonates (1; Ar ? X-Ph) react with trimethyl phosphite to give anionic intermediates which in the absence of electrophiles decompose to give carbene intermediates (3). The nature of the subsequent reaction products depends on the type and position of the substituents on the aromatic ring.ll1 When proton donors are present the initially formed anionic intermediates (2) give the quasi-phosphonium salts (4) which usually decompose to give the phohphonate-phosphates (5). although for the case of (1; Ar ? 4-MeOPh) formation of the phosphonates (6) was observed.     

The NMR spectra of porphyrins—19: 13C and proton NMR spectra of metal-free porphyrins with the Type-IX substituent orientation,and of their zinc(II) complexes

The ¹³C and proton NMR spectra of six porphyrins bearing the substituent orientation characteristic of the natural “Type-IX” arrangement are reported and assigned. Significant concentration effects in the spectra of the free base porphyrins, together with the broadening of the C_α (and occasionally C_β) carbon resonances due to NH tautomerism caused a significant loss of data in these spectra. However, the spectra of the corresponding zinc(II) porphyrins (with addition of excess pyrrolidine) show that both these extraneous effects are completely removed to give well-resolved spectra with accurately reproducible chemical shifts. These spectra are assigned and an analysis of the chemical shifts allows the deduction of substituent chemical shift (SCS) parameters for the peripheral substituents at the beta and meso carbons. There is no global effect of these beta substituents, the beta carbon SCS being confined to the immediate pyrrole ring, and the meso carbon SCS to the two adjacent pyrrole rings. The SCS parameters are analyzed and it is shown how they can be used to predict the peripheral and meso carbon chemical shifts of any porphyrin bearing the substituents discussed.     

The dithianyl group as a synthon in porphyrin chemistry: condensation reactions and preparation of formylporphyrins under basic conditions

Vilsmeier formylation is one of the most widely used substitution reactions for the functionalization of porphyrins. However, its utility is limited by the electrophilic/acidic reaction conditions, deactivation of the aromatic system and regiochemical problems, the requirement for metal complexes and necessity for subsequent demetalation under harsh conditions, and low functional group tolerance. To overcome these limitations, the dithianyl group has been utilized as a latent formyl synthon in porphyrin chemistry. 2-Formyl-1,3-dithiane can be used directly in pyrrole condensation reactions to regioselectively yield porphyrins with up to four dithianyl residues. Likewise, 5-dithianyldipyrromethane could be prepared quantitatively as a key building block for various porphyrin condensation reactions yielding the respective free base formylporphyrins after deprotection. Additionally, dithianyllithium can be used as a reagent for the direct aromatic substitution of metallo- and free base porphyrins under nucleophilic conditions.     

Thioketone‐Directed Palladium(II)‐Catalyzed C−H Arylation of Ferrocenes with Aryl Boronic Acids

A palladium(II)‐catalyzed thioketone‐chelation‐assisted direct C?H arylation of ferrocenes is described. With thioketone as an efficient directing group, various monoaryl‐ and diaryl‐substituted thiocarbonylferrocenes were obtained by palladium‐catalyzed direct C?H functionalization in high yields under mild and base‐free reaction conditions. Furthermore, the arylated thiocarbonylferrocene could undergo diverse transformations.