Carbonyl mediated fluorescence in aceno[n]helicenones and fluoreno[n]helicenes.

Helicenes are very attractive chiral non-planar polycyclic aromatic hydrocarbons possessing strong chiroptical properties. However, most of the helicenes absorb light mainly in the ultraviolet region, with only a small segment in the blue part of the visible spectrum. Furthermore, carbo[n]helicenes exhibit only weak luminescence that limits their utilization. Herein, we demonstrate that peripheral decoration of the helicene backbone with an aryl-carbonyl group shifts the absorption to the visible region and simultaneously improves their fluorescence quantum yields. We thus show that the carbonyl group, commonly considered as detrimental to emission, has the capability of improving optical and photophysical properties. Two different families, aceno[n]helicenones and fluoreno[n]helicenes, are presented with comprehensive spectrochemical characterization. TD-DFT calculations were implemented to clarify their electronic profiles. We show that increasing the helical length in aceno[n]helicenes increases absorption onset, g abs and g lum. Extension of the peripheral aromatic part in fluoreno[n]helicenes leads to a blue shift in both absorption and emission.

Self-Inclusion Complexation of Electron-Accepting Guest into Electron-Donating Cyclic Host by Photoexcitation.

Self-inclusion complexes consisting of host-guest conjugates are one of the unique supramolecular structures because they form in-state and out-state depending on the external stimuli. Despite many reports of the stimuli-responsive self-inclusion complex formation, study of the structural relaxation from out-state to in-state by photoexcitation has been unexplored. Herein, we report that an electron-donating host and an electron-accepting guest conjugate exhibits the structural relaxation from out-state to in-state by photoexcitation. Formation of the in-state in the excited state resulted in exciplex emission along with the locally excited emission from the out-state. Moreover, this structural relaxation by photoexcitation was suppressed not only by temperature, but also by the presence of guest molecules, resulting in changes in the ratio of the dual emission intensities.

Atroposelective Total Synthesis of Cihunamide B.

A short, atroposelective synthesis of cihunamide B (1) is reported. The feature of this report is the decagram-scale SNAr reaction of l-tryptophan derivatives, followed by atroposelective Larock macrocyclization. This strategy allowed the construction of a Trp-Trp cross-linkage with unprecedented atropisomerism. The atroposelectivity of this Larock macrocyclization has been investigated through a combination of experimental and computational chemistry, yielding detailed insights into the synthesis of biaryl linkages. It also enabled the concise synthesis of cihunamide B (1), which is expected to be a potential antibacterial agent.

OSPAR: A Corpus for Extraction of Organic Synthesis Procedures with Argument Roles.

There is a pressing need for the automated extraction of chemical reaction information because of the rapid growth of scientific documents. The previously reported works in the literature for the procedure extraction either (a) did not consider the semantic relations between the action and argument or (b) defined a detailed schema for the extraction. The former method was insufficient for reproducing the reaction, while the latter methods were too specific to their own schema and did not consider the general semantic relation between the verb and argument. In addition, they did not provide an annotated text that aligned with the structured procedure. Along these lines, in this work, we propose a corpus named organic synthesis procedures with argument roles (OSPAR) that is annotated with rolesets to consider the semantic relation between the verb and argument. We also provide rolesets for chemical reactions, especially for organic synthesis, which represent the argument roles of actions in the corpus. More specifically, we annotated 112 organic synthesis procedures in journal articles from Organic Syntheses and defined 19 new rolesets in addition to 29 rolesets from an existing language resource (Proposition Bank). After that, we constructed a simple deep learning system trained on OSPAR and discussed the usefulness of the corpus by comparing it with chemical description language (XDL) generated by a natural language processing tool, namely, SynthReader. While our system's output required more detailed parsing, it covered comparable information against XDL. Moreover, we confirmed that the validation of the output action sequence was easy as it was aligned with the original text.

Diastereoselective Rotaxane Synthesis with Pillar[5]arenes via Co-crystallization and Solid-State Mechanochemical Processes.

Chiral rotaxanes have attracted much attention in recent decades for their unique chirality based on their interlocked structures. Thus, selective synthesis methods of chiral rotaxanes have been developed. The introduction of substituents with chiral centers to produce diastereomers is a powerful strategy for the construction of chiral rotaxanes. However, in case of a small energy difference between the diastereomers, diastereoselective synthesis is extremely difficult. Herein, we report a new diastereoselective rotaxane synthesis method using solid-phase diastereoselective [3]pseudorotaxane formation and mechanochemical solid-phase end-capping reactions of the [3]pseudorotaxanes. By co-crystallization of stereodynamic planar chiral pillar[5]arene with stereogenic carbons at both rims and axles with suitable end groups and lengths, the [3]pseudorotaxane with a high diastereomeric excess (ca. 92% de) was generated in the solid state because of higher effective molarity with aid by packing effects and significant energy differences between [3]pseudorotaxane diastereomers. In contrast, the de of the pillar[5]arene was low in solution (ca. 10% de) because of a small energy difference between diastereomers. Subsequent end-capping reactions of the polycrystalline [3]pseudorotaxane with high de in solvent-free conditions successfully yielded rotaxanes while maintaining the high de generated by the co-crystallization.

Microfluidic platform using focused ultrasound passing through hydrophobic meshes with jump availability.

Applications in chemistry, biology, medicine, and engineering require the large-scale manipulation of a wide range of chemicals, samples, and specimens. To achieve maximum efficiency, parallel control of microlitre droplets using automated techniques is essential. Electrowetting-on-dielectric (EWOD), which manipulates droplets using the imbalance of wetting on a substrate, is the most widely employed method. However, EWOD is limited in its capability to make droplets detach from the substrate (jumping), which hinders throughput and device integration. Here, we propose a novel microfluidic system based on focused ultrasound passing through a hydrophobic mesh with droplets resting on top. A phased array dynamically creates foci to manipulate droplets of up to 300 µL. This platform offers a jump height of up to 10 cm, a 27-fold improvement over conventional EWOD systems. In addition, droplets can be merged or split by pushing them against a hydrophobic knife. We demonstrate Suzuki-Miyaura cross-coupling using our platform, showing its potential for a wide range of chemical experiments. Biofouling in our system was lower than in conventional EWOD, demonstrating its high suitability for biological experiments. Focused ultrasound allows the manipulation of both solid and liquid targets. Our platform provides a foundation for the advancement of micro-robotics, additive manufacturing, and laboratory automation.

Amino-Ene Click Reaction of Electron-Deficient π-Conjugated Molecules with Negative Activation Enthalpies.

An amino-ene click reaction is a type of aza-Michael addition reaction that is congruent with click chemistry in terms of its reaction efficiency and rate under mild conditions. The amino-ene click reaction is increasingly recognized as a prominent synthetic tool to form C-N bonds in the context of organic materials chemistry and polymer chemistry. Herein, an unconventional amino-ene click reaction with negative activation enthalpies, in which an electron-deficient π-conjugated molecule, such as a naphthalenediimide, reacts with an amine faster at lower temperatures is reported. The detailed study of the reaction mechanism reveals that the amino-ene click reaction proceeds via a pre-equilibrium reaction, the key to which is the formation of a stable reaction intermediate due to the solvation and charge delocalization on the π-core. By optimizing the reaction conditions, it was demonstrated that the amino-ene click reaction proceeded faster at 273 K than at 347 K, which was easily observed visually.

Synthesis of Cationic Azatriphenylene Derivatives by Electrochemical Intramolecular Pyridination and Characterization of Their Optoelectronic Properties.

Here, a facile and selective synthesis method for cationic azatriphenylene derivatives was established by electrochemical intramolecular cyclization, where atom-economical C-H pyridination without a transition-metal catalyst or an oxidant is a key step. The proposed protocol is a practical strategy for the late-stage introduction of cationic nitrogen (N+) into π-electron systems and broadens the scope of molecular design of N+-doped polycyclic aromatic hydrocarbons.

Adaptive Planar Chirality of Pillar[5]arenes Invertible by n-Alkane Lengths.

Chirality of host molecules can be induced and/or inverted by the guest molecules. However, the adapting chirality of hosts to the length of n-alkanes remains a great challenge because n-alkanes are neutral, achiral, and linear molecules, resulting in a weak interaction with most compounds. Herein, we report a system with chirality adapted to n-alkane lengths, using a pillar[5]arene-based macrocyclic host, S-Br, which contains five stereogenic carbons and five terminal bromine atoms on each rim. The electron-rich cavity of S-Br could include n-alkanes and the planar-chiral isomers sensitively inverted in response to the lengths of the complexed n-alkanes. The inclusion of a short n-alkane such as n-pentane made S-Br more inclined to be in the pS-form, whereas the inclusion of long n-alkanes such as n-heptane made the pR-form more favorable. The difference in the stability of the isomers was supported by the crystal structures and the theoretical calculations. Furthermore, temperature drives the adaptive chirality of S-Br with n-alkanes. An n-alkane with middle length, n-hexane, showed the dominance of the pR-form of S-Br at a higher temperature, whereas the pS-form was shown at a lower temperature.

Aggregation-induced circularly polarized phosphorescence of Pt(II) complexes with an axially chiral BINOL ligand.

A pair of chiral Pt(II) complexes coordinated by simple BINOL and bipyridine ligands displaying aggregation-induced phosphorescence and circularly polarized luminescence were characterized by X-ray crystallography and absorption and emission spectroscopies. The emission of the powder sample was reddish whereas the thin film dispersed in PMMA (fPf = 1 wt%) exhibited a white emission.

Highly chemoselective ligands for Suzuki-Miyaura cross-coupling reaction based on virtual ligand-assisted screening.

Ligand screening is a crucial step in the development of transition metal catalysis, as it involves identifying the optimal ligand for a particular reaction from a large pool of candidate molecules. Conventionally, this process is performed through an experimental trial-and-error, which can be time-consuming and resource-intensive in many cases. One of the ideal strategies for streamlining this process is a transition state theory (TST)-based approach, which aims to design optimal catalysts that results in the best energy profile for the desired reaction. However, the implementation of TST-based ligand screening remains challenging mainly due to the large number of potential ligands that need to be individually evaluated through quantum chemical calculations. In this study, we experimentally demonstrated a practical TST-based ligand screening in accordance with our virtual ligand-assisted (VLA) screening strategy. As a case study, the electronic anc steric features of phosphine ligands that maximize chemoselectivity in the Suzuki-Miyaura cross-coupling (SMC) reaction of p-chlorophenyl triflate were determined through quantum chemical calculations using virtual ligands, and several phosphine ligands were suggested to exhibit high chemoselectivity. Based on this suggestion, we successfully found that tri(1-adamantyl)phosphine and tri(neopentyl)phosphine show high to excellent selectivity for the C-Cl bond activation. This case study suggests that the VLA screening strategy could be a useful tool for ligand screening.

Predicting Highly Enantioselective Catalysts Using Tunable Fragment Descriptors.

Catalyst optimization processes typically rely on inductive and qualitative assumptions of chemists based on screening data. While machine learning models using molecular properties or calculated 3D structures enable quantitative data evaluation, costly quantum chemical calculations are often required. In contrast, readily available binary fingerprint descriptors are time- and cost-efficient, but their predictive performance remains insufficient. Here, we describe a machine learning model based on fragment descriptors, which are fine-tuned for asymmetric catalysis and represent cyclic or polyaromatic hydrocarbons, enabling robust and efficient virtual screening. Using training data with only moderate selectivities, we designed theoretically and validated experimentally new catalysts showing higher selectivities in a challenging asymmetric tetrahydropyran synthesis.

TEtraQuinolines: A Missing Link in the Family of Porphyrinoid Macrocycles.

Porphyrin contains four inwardly oriented nitrogen atoms. It is arguably the most ubiquitous multifunctional naturally occurring macrocycle that has inspired the design of novel nitrogen-containing heterocycles for decades. While cyclic tetramers of pyrrole, indole, and pyridine have been exploited as macrocycles in this category, quinoline has been largely neglected as a synthon. Herein, we report the synthesis of TEtraQuinoline (TEQ) as a 'missing link' in this N4 macrocycle family. In TEQs, four quinoline units are concatenated to produce an S4-symmetric architecture. TEQs are characterized by a highly rigid saddle shape, wherein the lone-pair orbitals of the four nitrogen atoms are not aligned in a planar fashion. Nevertheless, TEQs can coordinate a series of transition-metal cations (Fe2+, Co2+, Ni2+, Cu2+, Zn2+, and Pd2+). TEQs are inherently fluorescence-silent but become strongly emissive upon protonation or complexation of Zn(II) cations (ϕ = 0.71). TEQ/Fe(II) complexes can catalyze dehydrogenation and oxygenation reactions with catalyst loadings as low as 0.1 mol %.

A Twisted Chiral Cavitand with 5-Fold Symmetry and Its Length-Selective Binding Properties.

Controlling bottom-up syntheses from chiral seeds to construct architectures with specific chiralities is currently challenging. Herein, a twisted chiral cavitand with 5-fold symmetry was constructed by bottom-up synthesis using corannulene as the chiral seed and pillar[5]arene as the chiral wall. After docking between the seed and the wall, their dynamic chiralities (M and P) are fixed. Moreover, the formed hedges also exhibit M and P chirality. Through dynamic covalent bonding, the thermodynamically stable product is obtained selectively as a pair of enantiomers (MMM and PPP), where all three subcomponents, i.e., the corannulene, hedges, and pillar[5]arene, are tilted in the same direction. Furthermore, the twisted cavitand exhibits length-selective binding to alkylene dibromides, with three maximum binding constants being unexpectedly observed.

Real-time chirality transfer monitoring from statistically random to discrete homochiral nanotubes.

Real time monitoring of chirality transfer processes is necessary to better understand their kinetic properties. Herein, we monitor an ideal chirality transfer process from a statistically random distribution to a diastereomerically pure assembly in real time. The chirality transfer is based on discrete trimeric tubular assemblies of planar chiral pillar[5]arenes, achieving the construction of diastereomerically pure trimers of pillar[5]arenes through synergistic effect of ion pairing between a racemic rim-differentiated pillar[5]arene pentaacid bearing five benzoic acids on one rim and five alkyl chains on the other, and an optically resolved pillar[5]arene decaamine bearing ten amines. When the decaamine is mixed with the pentaacid, the decaamine is sandwiched by two pentaacids through ten ion pairs, initially producing a statistically random mixture of a homochiral trimer and two heterochiral trimers. The heterochiral trimers gradually dissociate and reassemble into the homochiral trimers after unit flipping of the pentaacid, leading to chirality transfer from the decaamine and producing diastereomerically pure trimers.

Quantum Chemical Calculations to Trace Back Reaction Paths for the Prediction of Reactants.

The long-due development of a computational method for the ab initio prediction of chemical reactants that provide a target compound has been hampered by the combinatorial explosion that occurs when reactions consist of multiple elementary reaction processes. To address this challenge, we have developed a quantum chemical calculation method that can enumerate the reactant candidates from a given target compound by combining an exhaustive automated reaction path search method with a kinetics method for narrowing down the possibilities. Two conventional name reactions were then assessed by tracing back the reaction paths using this new method to determine whether the known reactants could be identified. Our method is expected to be a powerful tool for the prediction of reactants and the discovery of new reactions.

Preparative-scale synthesis of nonacene.

During the last years we have witnessed progressive evolution of preparation of acenes with length up to dodecacene by on-surface synthesis in ultra-high vacuum or generation of acenes up to decacene in solid matrices at low temperatures. While these protocols with very specific conditions produce the acenes in amount of few molecules, the strategies leading to the acenes in large quantities dawdle behind. Only recently and after 70 years of synthetic attempts, heptacene has been prepared in bulk phase. However, the preparative scale synthesis of higher homologues still remains a formidable challenge. Here we report the preparation and characterisation of nonacene and show its excellent thermal and in-time stability.

Cyclodextrins with Multiple Pyrenyl Groups: An Approach to Organic Molecules Exhibiting Bright Excimer Circularly Polarized Luminescence.

We report a simple and effective approach to organic molecules exhibiting bright circularly polarized luminescence (CPL) by combining a chiral cyclic molecular scaffold and multiple excimer-enabling moieties. An α-cyclodextrin (CyD) scaffold was modified with six pyrenyl groups to obtain pyrene-cyclodextrins (PCDs) in a one-step synthesis from commercially available compounds. The PCDs exhibited high molar extinction coefficients (ϵ≈105  M-1  cm-1 ), polarized emission with a good dissymmetry factor (|glum |≈10-2 ), and quantum yield (Φf ≈0.5). Owing to the excellent photophysical properties of the PCDs, the circularly polarized luminescence brightness (BCPL ) reached 340 M-1  cm-1 . Photophysical and chiroptical studies of the PCDs with only five pyrene units and with linkers of various lengths connecting the CyD with the pyrene units revealed that the formation of a pyrene excimer in a spatially crowded environment is crucial for CPL anisotropy. This study paves the way for the development of bright CPL organic molecules.

Synthesis, Structure, and Dynamics of Chiral Eight-Membered Cyclic Molecules with Thienylene and Cyclopropylene Units Alternately Connected.

A rhodium(II)-catalyzed asymmetric cyclooligomerization of bifunctional monomers possessing triazolyl and vinyl groups at 2,3- and 3,4-positions on the thiophene ring is studied. Structurally interesting cyclic dimers in which thienylene and cyclopropylene units are alternately connected are obtained as the major components. The eight-membered rings in the center are non-planar and adopt a tub-shaped conformation. We also observe the phenomenon of racemization caused by a tub-to-tub ring-flipping, the activation energy of which is determined as 108 kJ mol-1 by electronic circular dichroism spectra measurement.

A semi-automated material exploration scheme to predict the solubilities of tetraphenylporphyrin derivatives.

Acceleration of material discovery has been tackled by informatics and laboratory automation. Here we show a semi-automated material exploration scheme to modelize the solubility of tetraphenylporphyrin derivatives. The scheme involved the following steps: definition of a practical chemical search space, prioritization of molecules in the space using an extended algorithm for submodular function maximization without requiring biased variable selection or pre-existing data, synthesis & automated measurement, and machine-learning model estimation. The optimal evaluation order selected using the algorithm covered several similar molecules (32% of all targeted molecules, whereas that obtained by random sampling and uncertainty sampling was ~7% and ~4%, respectively) with a small number of evaluations (10 molecules: 0.13% of all targeted molecules). The derived binary classification models predicted 'good solvents' with an accuracy >0.8. Overall, we confirmed the effectivity of the proposed semi-automated scheme in early-stage material search projects for accelerating a wider range of material research.