Impact of helical elongation of symmetric oxa[n]helicenes on their structural, photophysical, and chiroptical characteristics.

The adjustment of the main helical scaffold in helicenes is a fundamental strategy for modulating their optical features, thereby enhancing their potential for diverse applications. This work explores the influence of helical elongation (n = 5-9) on the structural, photophysical, and chiroptical features of symmetric oxa[n]helicenes. Crystal structure analyses revealed structural variations with helical extension, impacting torsion angles, helical pitch, and packing arrangements. Through theoretical investigations using density functional theory (DFT) calculations, the impact of helical extension on aromaticity, planarity distortion, and heightened chiral stability were discussed. Photophysical features were studied through spectrophotometric analysis, with insights gained through time-dependent DFT (TD-DFT) calculations. Following optical resolution via chiral high-performance liquid chromatography (HPLC), the chiroptical properties of both enantiomers of oxa[7]helicene and oxa[9]helicene were investigated. A slight variation in the main helical scaffold of oxa[n]helicenes from [7] to [9] induced an approximately three-fold increase in dissymmetry factors with the biggest values of|glum| of oxa[9]helicene (2.2 × 10-3) compared to|glum|of oxa[7]helicene (0.8 × 10-3), findings discussed and supported by TD-DFT calculations.

In-silico-assisted derivatization of triarylboranes for the catalytic reductive functionalization of aniline-derived amino acids and peptides with H2.

Cheminformatics-based machine learning (ML) has been employed to determine optimal reaction conditions, including catalyst structures, in the field of synthetic chemistry. However, such ML-focused strategies have remained largely unexplored in the context of catalytic molecular transformations using Lewis-acidic main-group elements, probably due to the absence of a candidate library and effective guidelines (parameters) for the prediction of the activity of main-group elements. Here, the construction of a triarylborane library and its application to an ML-assisted approach for the catalytic reductive alkylation of aniline-derived amino acids and C-terminal-protected peptides with aldehydes and H2 is reported. A combined theoretical and experimental approach identified the optimal borane, i.e., B(2,3,5,6-Cl4-C6H)(2,6-F2-3,5-(CF3)2-C6H)2, which exhibits remarkable functional-group compatibility toward aniline derivatives in the presence of 4-methyltetrahydropyran. The present catalytic system generates H2O as the sole byproduct.

Selective recognition between aromatics and aliphatics by cage-shaped borates supported by a machine learning approach.

Selective recognition between hydrocarbon moieties is a longstanding issue. Although we developed a π-pocket Lewis acid catalyst with high selectivity for aromatic aldehydes over aliphatic ones, a general strategy for catalyst design remains elusive. As an approach that transfers the molecular recognition based on multiple cooperative non-covalent interactions within the π-pocket to a rational catalyst design, herein, we demonstrate Lewis acid catalysts showing improved selectivity through the support of an ensemble algorithm with random forest, Ada Boost, and XG Boost as a machine learning (ML) approach. Using 7963 explanatory variables extracted from model hetero-Diels-Alder reactions, the ensemble algorithm predicted the chemoselectivity of unlearned catalysts. Experiments confirmed the prediction. The proposed catalyst shows the highest selective recognition, reminiscing enzymatic catalytic activity. Additionally, a SHapley Additive exPlanations (SHAP) method suggested that the selectivity originates from the polarizability and three-dimensional size of the catalyst. This insight leads to rational design guidelines for Lewis acid catalysts with dispersion forces.

Synthesis and Structural and Optical Behavior of Dehydrohelicene-Containing Polycyclic Compounds.

Dehydrohelicene-based molecules stand out as highly promising scaffolds and captivating chiroptical materials, characterized by their unique chirality. Their quasi-helical π-conjugated molecular architecture, featuring successively ortho-annulated aromatic rings, endows them with remarkable thermal stability and optical properties. Over the past decade, diverse approaches have emerged for synthesizing these scaffolds, reinvigorating this field, with anticipated increased attention in the coming years. This review provides a comprehensive overview of the historical evolution of dehydrohelicene chemistry since the pioneering work of Zander and Franke in 1969 and highlights recent advancements in the synthesis of various molecules incorporating dehydrohelicene motifs. We elucidate the intriguing structural features and optical merits of these molecules, occasionally drawing comparisons with their helicene or circulene analogs to underscore the significance of the bond between the helical termini.

Light-controlled pKa value of chiral Brønsted acid catalysts in enantioselective aza-Friedel-Crafts reaction.

Bis(dithienylethene)-based BINOL-derived phosphoric acid (DTE-BPA) has been developed as a light-controlled chiral organocatalyst for the first time. The photoinduced modulation of the reactivity and selectivity via the open/close isomerization of the DTE scaffold led to superior light-controlled ability in the enantioselective aza-Friedel-Crafts reaction of aldimines with indoles. DFT studies showed that photoisomerization is accompanied by a shift of 1.1 pKa units between the open and closed isomers.

Antifouling Brominated Diterpenoids from Japanese Marine Red Alga Laurencia venusta Yamada.

The marine red algal genus Laurencia has abundant halogenated secondary metabolites, which exhibit novel structural types and possess various unique biological potentials, including antifouling activity. In this study, we report the isolation, structure elucidation, and antifouling activities of two novel brominated diterpenoids, aplysin-20 aldehyde (1), 13-dehydroxyisoaplysin-20 (2), and its congeners. We screened marine red alga Laurencia venusta Yamada for their antifouling activity against the mussel Mytilus galloprovincialis. Ethyl acetate extracts of L. venusta from Hiroshima and Chiba, Japan, were isolated and purified, and the compound structures were identified using 1D and 2D NMR, HR-APCI-MS, IR, and chemical synthesis. Seven secondary metabolites were identified, and their antifouling activities were evaluated. Compounds 1, 2, and aplysin-20 (3) exhibited strong activities against M. galloprovincialis. Therefore, these compounds can be explored as natural antifouling drugs.

Bayesian Optimization-Assisted Screening to Identify Improved Reaction Conditions for Spiro-Dithiolane Synthesis.

Bayesian optimization (BO)-assisted screening was applied to identify improved reaction conditions toward a hundred-gram scale-up synthesis of 2,3,7,8-tetrathiaspiro[4.4]nonane (1), a key synthetic intermediate of 2,2-bis(mercaptomethyl)propane-1,3-dithiol [tetramercaptan pentaerythritol]. Starting from the initial training set (ITS) consisting of six trials sampled by random screening for BO, suitable parameters were predicted (78% conversion yield of spiro-dithiolane 1) within seven experiments. Moreover, BO-assisted screening with the ITS selected by Latin hypercube sampling (LHS) further improved the yield of 1 to 89% within the eight trials. The established conditions were confirmed to be satisfactory for a hundred grams scale-up synthesis of 1.

Photoswitchable Chiral Organocatalysts: Photocontrol of Enantioselective Reactions.

This study presents recent advances in photoswitchable chiral organocatalysts and their applications in the photomodulation of enantioselective reactions. Under irradiation with an appropriate wavelength of light, the E/Z-photoisomerization of the photoresponsive units on the catalysts leads to the control of the catalytic activity and/or selectivity of the enantioselective reactions. Additionally, this study elucidates the design, synthesis, and catalytic application of the fabricated azobenzene BINOL-based photoswitchable chiral phase-transfer catalysts. This account will provide insights into the appropriate design of a photoswitchable chiral organocatalyst that can achieve both good enantioselectivity and photocontrol.

Metal-Free Aerobic C-N Bond Formation of Styrene and Arylamines via Photoactivated Electron Donor-Acceptor Complexation.

This study processes a facile and green approach for the Markovnikov-selective hydroamination of styrene with naphthylamine through irradiation with UV LED light (365 nm) via an electron donor-acceptor complexation between naphthylamines and oxygen in situ. This protocol showcases the synthetic potential for aerobic C-N bond formation without using a metal catalyst and photosensitizer. Three naphthylamines were examined and afforded desired C-N bond formation product in moderate yield.

Two-Step Synthesis, Structure, and Optical Features of a Double Hetero[7]helicene.

A novel double aza-oxa[7]helicene was synthesized from the commercially available N1,N4-di(naphthalen-2-yl)benzene-1,4-diamine and p-benzoquinone in two steps. Combining the acid-mediated annulation with the electrochemical sequential reaction (oxidative coupling and dehydrative cyclization) afforded this double hetero[7]helicene. Moreover, the structural and optical features of this molecule have been studied using X-ray crystallographic analysis, and the absorption and emission behaviors were rationalized based on DFT calculations.

Atroposelective Synthesis of C-C Axially Chiral Compounds via Mono- and Dinuclear Vanadium Catalysis.

Axially chiral compounds with rotationally constrained σ-bonds that exhibit atropisomerism are lucrative synthetic targets because of their ubiquity in functional materials and natural products. The metal complex-catalyzed enantioselective fabrication of axially chiral scaffolds has been widely investigated, and thus far, considerable progress has been made. Over the past two decades, we have developed a highly efficient strategy for constructing axially chiral biarenol derivatives using chiral mono- and dinuclear vanadium complexes. These complexes are readily prepared from vanadium(IV) salts and Schiff base ligands (generated from the condensation of (S)-tert-leucine and di- or monoformyl-(R)-1,1'-bi-2-naphthol (BINOL) derivatives) under O2 and act as highly active catalysts for highly stereoselective C-C bond formation. In particular, the vanadium complex-catalyzed enantioselective oxidative coupling of 2-naphthols 1 under oxygen or in air, which is a green oxidant, affords the desired axially chiral molecules in high yields and high stereoselectivity (up to quantitative yield and 97% ee), along with water as the sole coproduct. This coupling reaction tolerated various functional groups (such as halogens, alkoxys, and boryls) and avoided overoxidation of coupling products.The key feature of dinuclear vanadium(V) catalysts such as (Ra,S,S)-5a is an outstanding mode of the homocoupling reaction, in which a single molecule of the catalyst activates two molecules of the starting material (e.g., 2-naphthols) simultaneously. With this "dual activation" mechanism, the oxidative coupling promoted by the dinuclear catalyst proceeds in an intramolecular manner. The homocoupling rate using 5 mol % of the dinuclear vanadium(V) complex (Ra,S,S)-5a was measured to be 111 times faster than that of the mononuclear vanadium(IV) complex (S)-4a bearing a half motif of the dinuclear vanadium complex.In the case of the heterocoupling reaction utilizing two different kinds of arenol derivatives, only a starting arenol having lower oxidation potential seems to be activated by the mononuclear vanadium complex. The reaction rate of the heterocoupling using either mono- or dinuclear vanadium complexes showed no difference to give the coupling product in high yields but with a different enantioselective manner; chiral mononuclear vanadium(V) complexes showed better enantioselectivites than that of the dinuclear vanadium(V) complexes. A competing heterocoupling study and a linear correlation between the ee of the mononucaler vanadium catalyst and ee of the heterocoupling suggested that the heterocoupling involves an intermolecular radical-anion coupling pathway.In this Account, we summarize the recent advances in vanadium-catalyzed coupling reactions that produced important chiral molecules, such as biresorcinols, polycyclic biphenols, oxa[9]helicenes, bihydroxycarbazoles, and C1-symmetrical biarenols, and their coupling reaction mechanisms. By pursuing vanadium catalysis, we believe numerous additional transformations as well as a renewed interest in catalytic and chemo-, regio-, and enantioselective aryl-aryl bond constructions will be manifested.

New anionic cobalt(III) complexes enable enantioselective synthesis of spiro-fused oxazoline and iodoacetal derivatives.

Anionic salicylimine-based cobalt (III) complexes featuring chiral ligands derived from isoleucine amino acids were used as efficient bifunctional phase-transfer catalysts for electrophilic iodination of enol ethers. The Brønsted acids of these complexes enabled the enantioselective asymmetric iodocyclization of enol ethers, furnishing spiro-fused oxazoline derivatives in high yields with up to 90:10 er. In addition, chiral cobalt (III) complexes catalyze the asymmetric intermolecular iodoacetalization of enol ethers with various alcohols to afford 3-iodoacetal derivatives in high yields with up to 92:8 er.

DAST-mediated ring-opening of cyclopropyl silyl ethers in nitriles: facile synthesis of allylic amides via a Ritter-type process.

A diethylaminosulfur trifluoride (DAST)-mediated ring-opening reaction of cyclopropyl silyl ethers in nitriles produced allylic amides in moderate to good yields (up to 87%). Time course studies using ReactIR and O-isotopic labeling mechanistic studies suggested that the present reaction occurs via a Ritter-type process, leading to the formation of allylic amides.

Photoswitchable Chiral Cation-Binding Catalyst: Photocontrol of Catalytic Activity on Enantioselective Aminal Synthesis.

Design of a suitable photoswitchable chiral cation-binding cage for the synthesis of optically active aminals was established using the azobenzene-BINOL hybrid oligoethylene glycol (ABOEG) through E/Z isomerization of the azobenzene unit. Under photoirradiation, both the catalytic activity and enantioselectivity of the generating (Z)-ABOEG are enhanced, in contrast to that of (E)-ABOEG, which can be attributed to the geometrically distinct coordination behavior between the metal cation and the oligoethylene glycols.

Bayesian optimization with constraint on passed charge for multiparameter screening of electrochemical reductive carboxylation in a flow microreactor.

Multiparameter screening of reductive carboxylation in an electrochemical flow microreactor was performed using a Bayesian optimization (BO) strategy. The developed algorithm features a constraint on passed charge for the electrochemical reaction, which led to suitable conditions being instantaneously found for the desired reaction. Analysis of the BO-suggested conditions underscored the physicochemical validity.

Electrochemical synthesis of heterodehydro[7]helicenes.

Dehydrohelicenes are some of the most attractive chiroptical materials with unique helical chirality. However, to our knowledge, there are no prior reports on their direct construction by asymmetric methods. In this work, sequential synthesis of aza-oxa-dehydro[7]helicenes via the electrochemical oxidative hetero-coupling of 3-hydoxycarbazoles and 2-naphthols followed by dehydrative cyclization and intramolecular C-C bond formation has been realized. In addition, an efficient enantioselective synthesis through chiral vanadium-catalyzed hetero-coupling and electrochemical oxidative transformations afforded heterodehydro[7]helicene without any racemization. The obtained dehydro[7]helicenes showed intense blue-colored circularly polarized luminescence (|glum| ≈ 2.5 × 10-3 at 433 nm). Thermodynamic and kinetic studies of the racemization barrier of heterodehydro[7]helicenes indicated significant chiral stability with ΔG‡> 140 kJ mol-1.

Bayesian optimization-driven parallel-screening of multiple parameters for the flow synthesis of biaryl compounds.

Traditional optimization methods using one variable at a time approach waste time and chemicals and assume that different parameters are independent from one another. Hence, a simpler, more practical, and rapid process for predicting reaction conditions that can be applied to several manufacturing environmentally sustainable processes is highly desirable. In this study, biaryl compounds were synthesized efficiently using an organic Brønsted acid catalyst in a flow system. Bayesian optimization-assisted multi-parameter screening, which employs one-hot encoding and appropriate acquisition function, rapidly predicted the suitable conditions for the synthesis of 2-amino-2'-hydroxy-biaryls (maximum yield of 96%). The established protocol was also applied in an optimization process for the efficient synthesis of 2,2'-dihydroxy biaryls (up to 97% yield). The optimized reaction conditions were successfully applied to gram-scale synthesis. We believe our algorithm can be beneficial as it can screen a reactor design without complicated quantification and descriptors.

Application of an Electrochemical Microflow Reactor for Cyanosilylation: Machine Learning-Assisted Exploration of Suitable Reaction Conditions for Semi-Large-Scale Synthesis.

Cyanosilylation of carbonyl compounds provides protected cyanohydrins, which can be converted into many kinds of compounds such as amino alcohols, amides, esters, and carboxylic acids. In particular, the use of trimethylsilyl cyanide as the sole carbon source can avoid the need for more toxic inorganic cyanides. In this paper, we describe an electrochemically initiated cyanosilylation of carbonyl compounds and its application to a microflow reactor. Furthermore, to identify suitable reaction conditions, which reflect considerations beyond simply a high yield, we demonstrate machine learning-assisted optimization. Machine learning can be used to adjust the current and flow rate at the same time and identify the conditions needed to achieve the best productivity.

Azopyridine-based chiral oxazolines with rare-earth metals for photoswitchable catalysis.

An azopyridine-based oxazoline was developed for utilizing azo group coordination and isomerization as a photoswitchable ligand. The ligand coordinated to rare-earth metal (RE) catalyst underwent efficient E/Z photoisomerization, suggesting tri- and bidentate coordination switching. The photoisomerization of the ligand enabled modulation of the enantioselectivity of an RE-catalyzed aminal forming reaction.

Chemo- and regioselective cross-dehydrogenative coupling reaction of 3-hydroxycarbazoles with arenols catalyzed by a mesoporous silica-supported oxovanadium.

Cross-dehydrogenative coupling between 3-hydroxycarbazoles and 2-naphthols has been achieved by using a mesoporous silica-supported oxovanadium catalyst.