Diphenylacetylene-Incorporating Octaphyrin: A Rigid Macrocycle with Readily Separable Conformational Isomers.

An expanded carbaporphyrinoid analogue, octaphyrin(2,1,1,1,2,1,1,1), containing two rigid diphenylacetylene moieties is reported. In contrast to traditional pyrrolic macrocycles where flexible conformers coexist in dynamic equilibrium, this macrocycle exists as two separable, conformationally stable stereoisomers, denoted as 1A and 1B. The conformational effect of both conformers, as well as their protonated forms, were thoroughly studied using NMR spectroscopy, UV-Vis, and single crystal X-ray diffraction analyses. Importantly, heating conformer 1B leads to its irreversible conversion to 1A, whereas in its protonated form, 1A·2MSA undergoes irreversible transformation to 1B·2MSA at lower temperatures. These temperature-dependent features establish a foundation for developing new accumulated heat sensors, as demonstrated by the use of the present octaphyrins as a customized thermochromic indicator in steam sterilization. The present study thus underscores how the conformational rigidity of these new polypyrrolic macrocycles imparts properties that are distinct from historically flexible expanded porphyrinoids.

Resolution of Expanded Porphyrinoids: A Path to Persistent Chirality and Appealing Chiroptical Properties.

Chirality is a fundamental characteristic of nature. Expanded porphyrinoids and their analogues offer an attractive platform for delving into the intricacies of chirality. Expanded porphyrinoids comprise pyrrolic macrocycles and related heterocyclic systems. As a class, expanded porphyrinoids are widely recognized for their flexible structural features, nontrivial coordination capabilities, and intriguing optical and electronic properties. With limited exceptions, their inherent conformational flexibility coupled with a low racemization barrier allows for the facile interchange between enantiomers. As a result, achieving the effective chiral resolution of individual enantiomers and the subsequent exploration of their chiroptical properties represents a significant challenge. This review summarizes strategies used to realize the chiral resolution of expanded porphyrinoids and the understanding of intrinsic chiroptical properties that has emerged from these separation efforts. It is our hope that this review will serve not only to codify our current understanding of chiral expanded porphyrinoids, but also inspire advances in the generalized area of chiral functional materials.

Phenanthrene-Incorporated Isoamethyrin: A Near-Planar Macrocycle That Display Enhanced Aromaticity via Protonation-Triggered Conformation Changes.

Controlling the aromaticity in expanded porphyrins is a forefront research topic, and the strategy of using protonation-triggered conformational changes to fine-tune electronic properties and aromaticity has yet to be generalized in rigid and planar expanded porphyrins. Here, we synthesized phenanthrene-incorporated isoamethyrins that possess near-planar conformations and nonaromatic characters. However, when methanesulfonic acid (MSA) was added, geometric deformations occurred to minimize the unfavorable strain, resulting in macrocycles that were weakly aromatic as a whole.

Di-2,7-pyrenidecaphyrin(1.1.0.0.0.1.1.0.0.0) and Its Bis-Organopalladium Complexes: Synthesis and Chiroptical Properties.

A non-aromatic expanded carbaporphyrinoid, incorporating two built-in 2,7-pyrenylene moieties was synthesized. The intrinsically labile structure was demonstrated by proton-triggered conformational changes between the figure-of-eight and quasi-Möbius conformers. Upon treatment with Pd(OAc)2 , the reaction produces two bis-PdII complexes with distinct coordination modes. Metal coordination serves to fix the macrocyclic frameworks with the net result that both bis-PdII complexes could be resolved by high performance liquid chromatography (HPLC) on a chiral stationary phase. The isolated enantiomers showed persistent chiroptical properties as evidenced by the intense response in the circular dichroism (CD) spectra and the record high absorption dissymmetry factors (gabs of up to 0.038) seen in the near-infrared spectral region. Moreover, the mutual interconversion of these two PdII complexes was found to be stereospecific and to favor the more stable isomers under weakly acidic conditions.

3,6-Carbazoylene Octaphyrin (1.0.0.0.1.0.0.0) and Its Bis-BF2 Complex.

3,6-Carbazole precursors were used to prepare an octaphyrin. The conformation and electronic structure of the system could be modulated through trifluoroacetate (TFA) protonation and BF2 complexation. The resulting nonaromatic macrocyclic complexes, 2-2TFA and 2-2BF2, displayed noteworthy photophysical properties. For instance, the diprotonated species 2-2TFA showed a strong panchromic absorption up to 800 nm, while the bis-BF2-chelated dipyrromethene (BODIPY)-like complex 2-2BF2 exhibited an intense visible absorption feature (ε535nm = 2.1 × 105 M-1 cm-1), as well as a relatively red-shifted emission at 640 nm characterized by a large Stokes shift. It was found that 2-2BF2 could be used to construct a high-quality organic microlaser that functions under optical pumping. The present study highlights the potential utility of expanded porphyrins as possible laser dyes.

Structural basis for the dimerization mechanism of human transcription factor E3.

The transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) is a member of the microphthalmia (MiT/TFE) transcription factor family. Dysregulation of TFE3 due to chromosomal abnormalities is associated with a subset of human renal cell carcinoma. Little structural information of this key transcription factor has been reported. In this study, we determined the crystal structure of the helix-loop-helix leucine zipper (HLH-Lz) domain of human TFE3 to a resolution of 2.6 Å. The HLH-Lz domain is critical for the dimerization and function of TFE3. Our structure showed that the conserved HLH region formed a four-helix bundle structure with a predominantly hydrophobic core, and the leucine zipper region contributed to the function of TFE3 by promoting dimer interaction and providing partner selectivity. Together, our results elucidated the dimerization mechanism of this important transcription factor, providing the structural basis for the development of inhibiting strategies for treating TFE3 dysregulated diseases.

Carbazole-Containing Carbadecaphyrins: Non-aromatic Expanded Porphyrins that Undergo Proton-Triggered Conformational Changes.

A pair of meso-unsubstituted expanded carbaporphyrins containing two carbazole moieties were prepared in high isolated yields (82 and 76 %, respectively). The two macrocycles, namely 3 and 4, differ with respect to their substitution at the carbazole N-atoms i. e. by H and i-Bu, respectively. As prepared in their free-base forms, macrocycles 3 and 4 adopt figure-of-eight conformations and are best characterized as 40 π-electron, non-aromatic species possessing a decaphyrin(1.1.0.0.0.1.1.0.0.0) skeleton. Protonation of 3 with either trifluoroacetic acid (TFA) or perchloric acid (HClO4 ) produces a parallelogram-shaped structure. A similar structure is produced when N-functionalized system 4 is treated with TFA. In contrast, protonation of 4 with HClO4 leads it to adopt a twisted Möbius strip-like structure in the solid state, thus allowing access to three distinct conformational states as a function of the conditions.

Self-Assembled Cagelike Receptor That Binds Biologically Relevant Dicarboxylic Acids via Proton-Coupled Anion Recognition.

We report here a fully organic, self-assembled dimeric receptor, constructed from acyclic naphthyridyl-polypyrrolic building blocks. The cagelike dimer is stable in the solid state, in solution, and in gas phase, as inferred from X-ray diffraction and spectroscopic analyses. This system acts as a receptor for oxalic acid, maleic acid, and malonic acid in the solid state and in THF solution. In contrast, acetic acid, propionic acid, adipic acid, and succinic acid, with pKa values > ca. 2.8, were not bound effectively within the cagelike cavity. It is speculated that oxalic acid, maleic acid, and malonic acid serve to protonate the naphthyridine moieties of the host, which then favors binding of the corresponding carboxylate anions via hydrogen-bonding to the pyrrolic NH protons. The present naphthyridine-polypyrrole dimer is stable under acidic conditions, including in the presence of 100 equiv trifluoroacetic acid (TFA), p-toluenesulfonic acid (PTSA), H2SO4, and HCl. However, disassembly may be achieved by exposure to tetrabutylammonium fluoride (TBAF). Washing with water then regenerates the cage. This process of assembly and disassembly could be repeated >20 times with little evidence of degradation. The reversible nature of the present system, coupled with its dicarboxylic acid recognition features, leads us to suggest it could have a role to play in effecting the controlled "capture" and "release" of biologically relevant dicarboxylic acids.

Excitonically Coupled Cyclic BF2 Arrays of Calix[8]- and Calix[16]phyrin as Near-IR-Chromophores.

Two giant calix[n]phyrin derivatives namely calix[8]- (4) and calix[16]phyrin (5), involving two and four BF2 units, respectively, were prepared through the condensation of the bis-naphthobipyrrolylmethene-BF2 complex (3) with pentafluorobenzaldehyde. Calix[n]phyrins 4 and 5 display extremely high extinction coefficients (3.67 and 4.82×105 m-1 cm-1 , respectively) in the near-IR region, which was taken as initial evidence for strong excitonic coupling within these cyclic multi-chromophoric systems. Detailed insights into the effect of excitonic coupling dynamics on the electronic structure and photophysical properties of the macrocycles came from fluorescence, time-correlated single-photon counting (TCSPC) and transient absorption (TA) measurements. Support for these experimental findings came from theoretical studies. Theory and experiment confirmed that the coupling between the excitons depends on the specifics of the calix[n]phyrin structure, not just its size.

Nickel-Catalyzed Direct Synthesis of Aryl Olefins from Ketones and Organoboron Reagents under Neutral Conditions.

Nickel-catalyzed addition of arylboron reagents to ketones results in aryl olefins directly. The neutral condition allows acidic protons of alcohols, phenols, and malonates to be present, and fragile structures are also tolerated.

Palladium-Catalyzed Heteroarylation and Concomitant ortho-Alkylation of Aryl Iodides.

Three-component couplings were achieved from common aryl halides, alkyl halides, and heteroarenes under palladium and norbornene co-catalysis. The reaction forges hindered aryl-heteroaryl bonds and introduces ortho-alkyl groups to aryl rings. Various heterocycles such as oxazoles, thiazoles and thiophenes underwent efficient coupling. The heteroarenes were deprotonated in situ by bases without the assistance of palladium catalysts.

Palladium-Catalyzed Direct Cyclopropylation of Heterocycles.

Many 1,3-azoles and thiophenes are directly cyclopropylated in the presence of a simple palladium catalyst. The relative configuration on the three-membered rings is retained in the products. Thus, the cyclopropyl-halide bond undergoes concerted oxidative addition to palladium(0) and cyclopropyl radicals are not involved in the productive pathway.

Synthesis of substituted pyridines from cascade [1 + 5] cycloaddition of isonitriles to N-formylmethyl-substituted enamides, aerobic oxidative aromatization, and acyl transfer reaction.

A novel strategy for de novo synthesis of pyridines featuring an unprecedented α-addition of aldehyde and enamide to isonitrile as a key step is described. Under mild conditions, a cascade reaction involving Zn(OTf)2-promoted [1 + 5] cycloaddition of isonitrile with N-formylmethyl-substituted enamide, facile aerobic oxidative aromatization and intermolecular acyl transfer from the pyridinium nitrogen to the 5-hydroxy oxygen, and finally acylation of the 4-amino group by an external acyl chloride efficiently afforded 2-substituted 4-acylamino-5-acyloxypyridines in good to excellent yields.

Synthesis of multifunctionalized 1,2,3,4-tetrahydropyridines, 2,3-dihydropyridin-4(1H)-ones, and pyridines from tandem reactions initiated by [5+1] cycloaddition of N-formylmethyl-substituted enamides to isocyanides: mechanistic insight and synthetic application.

Tandem reactions for the efficient synthesis of multifunctionalized 1,2,3,4-tetrahydropyridines, 2,3-dihydropyridin-4(1H)-ones, and pyridine derivatives have been developed and reaction mechanisms have been investigated. Synthetic cascades are initiated by the Zn(OTf)2-mediated [5+1] cycloaddition of N-formylmethyl-substituted tertiary enamides to isocyanides, thus leading to the versatile heterocyclic enamino imine intermediates. Interception of the intermediates by diastereoselective reduction of imine functionality with Me4NBH(OAc)3 afforded 1,6-disubstituted trans-3-hydroxy-4-arylamino- or -alkylamino-1,2,3,4-tetrahydropyridines, whereas acylation of the imino group followed by acidic hydrolysis produced 1,6-disubstituted 3-acyloxy-2,3-dihydropyridin-4(1H)-ones. Aerobic oxidation led to the aromatization followed by intermolecular acyl-group transfer from the pyridinium nitrogen to the 3-hydroxy moiety, thereby yielding substituted 3-acyloxy-4-aminopyridines. Synthetic potentials of the resulting products have been demonstrated by expedient and highly stereoselective synthesis of cis,cis-4,5-dihydroxy-2-phenylpiperidine and trans,trans-4-amino-5-hydroxy-2-phenylpiperidine compounds, which are important in medicinal chemistry, through simple and practical reduction reactions.

Nickel-Catalyzed Reductive Cross-Coupling of Aryl Bromides with Vinyl Acetate in Dimethyl Isosorbide as a Sustainable Solvent.

A nickel-catalyzed reductive cross-coupling has been achieved using (hetero)aryl bromides and vinyl acetate as the coupling partners. This mild, applicable method provides a reliable access to a variety of vinyl arenes, heteroarenes, and benzoheterocycles, which should expand the chemical space of precursors to fine chemicals and polymers. Importantly, a sustainable solvent, dimethyl isosorbide, is used, making this protocol more attractive from the point of view of green chemistry.

Kinetic trapping of a cobalt(ii) metallocage using a carbazole-containing expanded carbaporphyrinoid ligand.

The meso-unsubstituted expanded porphyrinoid 3, incorporating two carbazole moieties, acts as an effective ligand for Co(ii) and permits the isolation and X-ray diffraction-based characterization of a 6 : 3 metal-to-ligand metallocage complex that converts spontaneously to the constituent 2 : 1 metal-to-ligand metalloring species in chloroform solution. The discrete metalloring is formed directly when the Co(ii) complex is crystallized from supersaturated solutions, whereas crystallization from more dilute solutions favors the metallocage. Studies with two other test cations, Pd(ii) and Zn(ii), revealed exclusive formation of the monomeric metalloring complexes with no evidence of higher order species being formed. Structural, electrochemical and UV-vis-NIR absorption spectral studies provide support for the conclusion that the Pd(ii) complex is less distorted and more effectively conjugated than its Co(ii) and Zn(ii) congeners, an inference further supported by TD-DFT calculations. The findings reported here underscore how expanded porphyrins can support coordination modes, including bimetallic complexes and self-assembled cage structures, that are not necessarily easy to access using more traditional ligand systems.

Controlled assembly of a bicyclic porphyrinoid and its 3-dimensional boron difluoride arrays.

A fully conjugated cryptand-like bicyclic porphyrinoid ligand 4, incorporating three carbazole linkages and four dipyrrin moieties, was prepared via the acid-catalysed condensation of an extended 2,2'-bipyrrole analogue containing a central carbazole moiety and 3,4-diethyl-2,5-diformylpyrrole in 79% isolated yield. This new cryptand-like system acts as an effective ligand and allows for complexation of BF2 (boron difluoride) subunits. Three BODIPY arrays, containing two, three, and four BF2 subunits, namely 4·2BF2, 4·3BF2 and 4·4BF2, could thus be isolated from the reaction of 4 with BF3·Et2O in the presence of triethylamine at 110 °C, albeit in relatively low yield. As prepared, bicycle 4 is characterized by a rigid C 2 symmetric structure as inferred from VT NMR spectroscopic analyses. In contrast, the three BODIPY-like arrays produced as the result of BF2 complexation are conformationally flexible and unsymmetric in nature as deduced from similar analyses. All four products, namely 4, 4·2BF2, 4·3BF2 and 4·4BF2, were characterized by means of single crystal X-ray diffraction analyses. Tetramer 4·4BF2 gives rise to a higher extinction coefficient (by 2.5 times) relative to the bis- and tris-BODIPY arrays 4·2BF2 and 4·3BF2. This was taken as evidence for stronger excitonic coupling in the case of 4·4BF2. All three BODIPY-like arrays proved nearly non-fluorescent, as expected given their conformationally mobile nature. The efficiency of reactive oxygen species (ROS) generation was also determined for the new BODIPY arrays of this study.

1,4-Phenylene-Incorporated Decaphyrin(1.0.1.0.0.1.0.1.0.0): Synthesis, Structure, and Topological Chirality.

Expanded porphyrins represent emerging structures in realizing topological chirality; however, their inherent flexibility has hampered the effective chiral resolution. Herein, we rationally designed a decaphyrin 9, which could be separated into its enantiomers in the free-base form. The enantiomers showed noteworthy chiroptical properties, e.g., the intense circular dichroism response in the visible spectrum, and high absorption dissymmetry factors (gabs) of 0.036 at 618 nm. Theoretical analyses further explained the origin of the high gabs value.

Enhancing room-temperature phosphorescence via intermolecular charge transfer in dopant-matrix systems.

Some specific organic dopants have been found to form intermolecular charge transfer complexes with phosphorescence-inactive organic matrices to mediate intersystem crossing of the organic matrices and thus activate room-temperature phosphorescence of the organic matrices. This method of boosting intersystem crossing paves the way for high-performance organic room-temperature phosphorescent materials.

Nickel-catalyzed asymmetric reductive arylation of α-chlorosulfones with aryl halides.

We report an asymmetric Ni-catalyzed reductive cross-coupling of aryl/heteroaryl halides with racemic α-chlorosulfones to afford enantioenriched sulfones. The reaction tolerates a variety of functional groups under mild reaction conditions, which complements the current methods. The utility of this work was demonstrated by facile late-stage functionalization of commercial drugs.