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.

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.

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.

Catalytic aerobic photooxidation of triarylphosphines using dibenzo-fused 1,4-azaborines.

Although dibenzo-fused 1,4-heteroaromatics are utilized as strongly reducing photocatalysts in organic synthesis and polymerization, they have rarely been employed in catalytic photooxidation. Moreover, to date, their boron-analogs, dibenzo-fused 1,4-azaborines (DBABs), have not been applied in photocatalysis despite their promising potential as photocatalysts. Accordingly, herein, aerobic photooxidation of triarylphosphines (Ar3P) was performed using DBABs as photocatalysts. The reaction smoothly proceeded in an aprotic solvent, and phosphine oxides were obtained in appropriate yields. Density functional theory calculations suggested that DBAB captured and activated phosphadioxirane intermediates, which were generated by the interaction of Ar3P with 1O2, at the Lewis acidic boron center.

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.

Superior catalytic performance of intermetallic CaPt2 nanoparticles supported on titanium group oxides in hydrogenation of ketones to alcohols.

Intermetallic CaPt2 nanoparticles, supported on titanium group oxides, were prepared using a molten salt method with CaH2 as both the reducing agent and the calcium source. The nanoparticles exhibited superior catalytic activity compared to a commercial Pt/C catalyst in the hydrogenation of ketones to alcohols, which could be promoted by electron-rich Pt sites in CaPt2.

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.

Positive outcome of first-line therapy for a SMARCA4-deficient thoracic sarcomatoid tumor.

SMARCA4-deficient thoracic sarcomatoid tumor is a rare malignancy indicating some characteristics of a smoking-related disease. The purpose of this report is to describe a case of aggressive thoracic tumor with loss of immunochemical SMARCA4 expression and detail the results of our treatment regimen. The patient was a 58-year-old male and clinicopathologically diagnosed with a SMARCA4-deficient thoracic sarcomatoid tumor. Pembrolizumab plus carboplatin and pemetrexed resulted in significant response. This combination therapy showed potential for first-line systemic treatment of SMARCA4-deficient thoracic sarcomatoid tumors.

Correction: Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence.

Correction for 'Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence' by Masaru Kondo et al., Chem. Commun., 2020, 56, 1259-1262, DOI: 10.1039/C9CC08526B.

A survey of blood transfusion errors in Aichi Prefecture in Japan: Identifying major lapses threatening the safety of transfusion recipients.

BACKGROUND: Despite recent progress in blood systems, transfusion errors can occur at any time from the moment of collection through to the transfusion of blood and blood products. This study investigated the actual statuses of blood transfusion errors at institutions of all sizes in Aichi prefecture. MATERIALS AND METHODS: We investigated 104 institutions that perform 98 % of the blood transfusions in Aichi prefecture, and investigated the errors (incidents/accidents) that occurred at these facilities over 6 months (April to September, 2017). Incident/accident data were collected from responses to questionnaires sent to each institution; these were classified according to the categories and risk levels. RESULTS: Ninety-seven of the 104 institutions (93.3 %) responded to the questionnaire; a total of 688 incidents/accidents were reported. Most (682 cases; 99.2 %), were classified as risk level 2; however, 6 were level 3 and over, which included problems with autologous transfusion and inventory control. Approximately one-half of the incidents/accidents (394 cases; 57.3 %), were related to verification and the actual administration of blood products at the bedside; more than half of these incidents/accidents occurred at large-volume institutions. Meanwhile, a high frequency of incidents/accidents related to transfusion examination and labeling of blood products was observed at small- or medium-sized institutions. The reasons for most of these errors were simple mistakes and carelessness by the medical staff. CONCLUSIONS: Our results emphasize the importance of education, operational training, and compliance instruction for all members of the medical staff despite advances in electronic devices meant to streamline transfusion procedures.

Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence.

A highly atom-economical enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence has been established by using a flow system. Suitable flow conditions were explored through reaction screening of multiple parameters using machine learning. Eventually, functionalized chiral spirooxindole analogues were obtained in high yield with good ee as a single diastereomer within one minute.

Room-Temperature, Metal-Free, and One-Pot Preparation of 2H-Indazoles through a Mills Reaction and Cyclization Sequence.

The Mills reaction and cyclization of readily available 2-aminobenzyl alcohols and nitrosobenzenes using thionyl bromide provided 2H-indazoles in up to 88 % yields. In the metal-free process, acetic acid played a crucial role for the both Mills reaction and cyclization. A brominated 2H-indazole could also be obtained through the one-pot sequence.

Enantioselective conjugate addition of an α,α-dithioacetonitrile with nitroalkenes using chiral bis(imidazoline)-Pd complexes.

The enantioselective conjugate addition reaction of an α,α-dithioacetonitrile with nitroalkenes was catalysed by chiral bis(imidazoline)-palladium pincer-type complexes. The reaction was applicable to various nitroalkenes to afford products in good yield with high enantioselectivity. The obtained products can be converted to γ-lactam and biologically active rolipram.

Metallaphotoredox Difluoromethylation of Aryl Bromides.

Herein, we report a convenient and broadly applicable strategy for the difluoromethylation of aryl bromides by metallaphotoredox catalysis. Bromodifluoromethane, a simple and commercially available alkyl halide, is harnessed as an effective source of difluoromethyl radical by silyl-radical-mediated halogen abstraction. The merger of this fluoroalkyl electrophile activation pathway with a dual nickel/photoredox catalytic platform enables the difluoromethylation of a diverse array of aryl and heteroaryl bromides under mild conditions. The utility of this procedure is showcased in the late-stage functionalization of several drug analogues.

Direct catalytic enantioselective Mannich-type reaction of α,α-dithioacetonitriles with imines using chiral bis(imidazoline)-Pd complexes.

The first highly enantioselective reaction of α,α-dithioacetonitriles with imines has been developed. Good yields and enantioselectivity were observed for the reaction of various imines using chiral bis(imidazoline) catalysts. The obtained products can be converted into ß-aminonitrile or 1,3-diaminoketone.