Asymmetric Reductive Amination of α-Keto Acids Using Ir-Based Hydrogen Transfer Catalysts: An Access to Unprotected Unnatural α-Amino Acids.

A direct asymmetric reductive amination of α-keto acids catalyzed by Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand is described. The combined use of optically active 2-phenyglycinol as an aminating agent is effective for the chemo- and stereoselective transfer hydrogenation using formic acid. The subsequent elimination of the hydroxyethyl moiety by orthoperiodic acid can afford various unprotected α-amino acids in satisfactory isolated yields (20 examples) with excellent optical purities (up to >99% ee).

Recent Developments in Reactions and Catalysis of Protic Pyrazole Complexes.

Protic pyrazoles (N-unsubstituted pyrazoles) have been versatile ligands in various fields, such as materials chemistry and homogeneous catalysis, owing to their proton-responsive nature. This review provides an overview of the reactivities of protic pyrazole complexes. The coordination chemistry of pincer-type 2,6-bis(1H-pyrazol-3-yl)pyridines is first surveyed as a class of compounds for which significant advances have made in the last decade. The stoichiometric reactivities of protic pyrazole complexes with inorganic nitrogenous compounds are then described, which possibly relates to the inorganic nitrogen cycle in nature. The last part of this article is devoted to outlining the catalytic application of protic pyrazole complexes, emphasizing the mechanistic aspect. The role of the NH group in the protic pyrazole ligand and resulting metal-ligand cooperation in these transformations are discussed.

Asymmetric Transfer Hydrogenative Amination of Benzylic Ketones Catalyzed by Cp*Ir(III) Complexes Bearing a Chiral N-(2-Picolyl)sulfonamidato Ligand.

A convenient asymmetric reductive amination of benzylic ketones (α-arylated ketones) catalyzed by newly designed Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand was developed. Using readily available ß-amino alcohols as chiral aminating agents, a range of benzo-fused and acyclic ketones were successfully reduced with formic acid in methanol at 40 °C to afford amines with favorable chemo- and diastereoselectivities. The amino alcohol-derived chiral auxiliary was easily removed by mild periodic oxidants, leading to optically active primary ß-arylamines without erosion of the optical purity (up to 97% ee). The excellent catalytic performance was retained even upon lowering the amount of catalyst to a substrate/catalyst (S/C) ratio of 20,000, and the amination could be performed on a large scale exceeding 100 g. The precise hydride transfer to iminium species generated from the ketonic substrate and the chiral amine counterpart was suggested by the mechanistic studies on stoichiometric reactions of isolable hydridoiridium complexes and model intermediates such as N,O-acetal, enamine, and iminium compounds.

Range-Measurement Sensor to Improve the Authentication Workflow for Users of a Hospital Information System: A Proof-of-Concept Study.

In this study, we developed an authentication rangefinder (AR) system for hospital information system (HIS) terminals to support the user authentication workflows. The logoff process of the AR system is triggered if no object is placed at least 90 cm in front of the HIS terminal laptop for ≥5 s. We conducted an anonymous survey of medical staff who used the AR system. 33/42(78%) respondents acknowledged an improvement in the logoff process. This study indicates that the AR system improves the user authentication workflow.

Design and Evaluation of a Smartphone Medical Guidance App for Outpatients of Large-Scale Medical Institutions: Retrospective Observational Study.

BACKGROUND: The greatest stressor for outpatients is the waiting time before an examination. If the patient is able to use their smartphone to check in with reception, the patient can wait for their examination at any location, and the burden of waiting can be reduced. OBJECTIVE: This study aimed to report the system design and postintroductory outcomes of the Tori RinRin (TR2) system that was developed to reduce outpatient burden imposed by wait times before examination. METHODS: The TR2 system was introduced at Tottori University Hospital, a large medical facility that accepts a daily average of 1500 outpatients. The system, which links the hospital's electronic medical record database with patients' mobile devices, has the following functions: (1) GPS-based examination check-in processing and (2) sending appointment notification messages via a cloud notification service. In order to evaluate the usefulness of the TR2 system, we surveyed the utilization rate of the TR2 system among outpatients, implemented a user questionnaire, and polled the average time required for patients to respond to call notifications about their turn. RESULTS: The 3-month average of TR2 users 9 months after the TR 2 system introduction was 17.9% (14,536/81,066). In an investigation of 363 subjects, the mean examination call message response time using the TR2 system was 31 seconds (median 14 seconds). Among 166 subjects who responded to a user survey, 86.7% (144/166) said that the system helped reduce the burden of waiting time. CONCLUSIONS: The app allowed 17.9% of outpatients at a large medical facility to check in remotely and wait for examinations anywhere. Hence, it is effective in preventing the spread of infection, especially during pandemics such as that of coronavirus disease. The app reported in this study is beneficial for large medical facilities striving to reduce outpatient burden imposed by wait times.

Synthesis and Characterization of White-Light Luminescent End-Capped Polyimides Based on FRET and Excited State Intramolecular Proton Transfer.

N-cyclohexylphthalimide-substituted trifluoroacetylamino (CF3CONH-) group (3TfAPI), which forms an intramolecular hydrogen bond, was synthesized, and it exhibited a bright yellow fluorescence owing to the excited-state intramolecular proton transfer (ESIPT) in the solution and crystalline states. In addition, CF3CONH-substituted phthalic anhydride (3TfAPA) was synthesized, which was attached to the termini of a blue-fluorescent semi-aromatic polyimide (PI) chain. Owing to the efficient Förster resonance energy transfer (FRET) occurring from the main chain to the termini and the suppression of deprotonation (anion formation) at the 3TfAPA moiety by H2SO4 doping, the resulting PI films display bright white fluorescence. Moreover, the enhancement of the chain rigidity by substituting the diamine moiety results in an increase in the quantum yield of white fluorescence (Φ) by a factor of 1.7, due to the suppression of local molecular motion. This material design strategy is promising for preparing thermally stable white-light fluorescent PIs applicable to solar spectral convertors, displays, and ICT devices.

Oxy-tethered Cp*Ir(III) complex as a competent catalyst for selective dehydrogenation from formic acid.

A bifunctional tethered iridium catalyst containing a 1,2-diphenylethylenediamine framework was synthesised for the first time. The ethereal tether chain was easily constructed via the intramolecular oxydefluorination of a perfluorophenylsulfonyl substituent by using a modified 1,2,3,4,5-pentamethylcyclopentadienyl ligand with a hydroxyalkyl chain. The conformationally constrained structure could hamper deactivation pathways in the catalytic hydrogen generation from formic acid, leading to advanced durability and complete conversion.

Detecting Adverse Drug Events Through the Chronological Relationship Between the Medication Period and the Presence of Adverse Reactions From Electronic Medical Record Systems: Observational Study.

BACKGROUND: Medicines may cause various adverse reactions. An enormous amount of money and effort is spent investigating adverse drug events (ADEs) in clinical trials and postmarketing surveillance. Real-world data from multiple electronic medical records (EMRs) can make it easy to understand the ADEs that occur in actual patients. OBJECTIVE: In this study, we generated a patient medication history database from physician orders recorded in EMRs, which allowed the period of medication to be clearly identified. METHODS: We developed a method for detecting ADEs based on the chronological relationship between the presence of an adverse event and the medication period. To verify our method, we detected ADEs with alanine aminotransferase elevation in patients receiving aspirin, clopidogrel, and ticlopidine. The accuracy of the detection was evaluated with a chart review and by comparison with the Roussel Uclaf Causality Assessment Method (RUCAM), which is a standard method for detecting drug-induced liver injury. RESULTS: The calculated rates of ADE with ALT elevation in patients receiving aspirin, clopidogrel, and ticlopidine were 3.33% (868/26,059 patients), 3.70% (188/5076 patients), and 5.69% (226/3974 patients), respectively, which were in line with the rates of previous reports. We reviewed the medical records of the patients in whom ADEs were detected. Our method accurately predicted ADEs in 90% (27/30patients) treated with aspirin, 100% (9/9 patients) treated with clopidogrel, and 100% (4/4 patients) treated with ticlopidine. Only 3 ADEs that were detected by the RUCAM were not detected by our method. CONCLUSIONS: These findings demonstrate that the present method is effective for detecting ADEs based on EMR data.

A diazene-bridged diruthenium complex with structural restraint defined by single meta-diphosphinobenzene.

Creation of confined coordination spaces with controlled flexibility is of importance in mimicking enzymatic reactions. We found that a simple, non-chelating 1,3-bis(diphenylphosphino)benzene (DPPBz) assembled two Cp*Ru units to give a dinuclear complex, wherein only one DPPBz supports an open framework without metal-metal bonding. Subsequent treatment with an excess of hydrazine resulted in formal 2e-/2H+ transfer from hydrazine to afford a diazene-bridged complex featuring intramolecular NHCl hydrogen bonds. In constrast, a monophosphine failed to stabilize the diazene-bridged dinuclear structure due to the lack of the enforcement of the conformation.

Open clamshell dinuclear palladium(ii) complexes possessing out-of-plane anisotropy.

Double cyclometalation of planar, oligomeric phenylpyridines yielded dinuclear palladium(ii) complexes with novel out-of-plane anisotropy. An X-ray crystal structure analysis revealed that the complexes exhibit concave-convex geometry, and 1H NMR measurement evidenced the occurrence of stable out-of-plane anisotropy. The dipole moment and Pd-Pd interaction were investigated by theoretical calculations.

A Strategy toward Cyclic Topologies Based on the Dynamic Behavior of a Bis(hindered amino)disulfide Linker.

A simple and efficient method to generate macrocyclic structures has been developed based on the dynamic behavior of the linker bis(2,2,6,6-tetramethylpiperidin-1-yl)disulfide (BiTEMPS). The prime linear structure was transformed into a (macro)cycle using the following sequence: 1) thiol-ene reaction with a BiTEMPS derivative to afford the linear precursor, then 2) an entropy-driven transformation induced by diluting and heating. The radicals generated from BiTEMPS upon heating are highly tolerant toward a variety of chemical species, including oxygen and olefins, but they exhibit high reactivity in exchange reactions, which can be applied to the topology transformation of various skeletons. The advantages of the present method, namely, its procedural simplicity and substrate versatility, are demonstrated by the gram-scale synthesis of cyclic compounds with low and relatively high molecular weight.

Half-Sandwich Iridium Complexes Bearing a Diprotic Glyoxime Ligand: Structural Diversity Induced by Reversible Deprotonation.

Synthesis and deprotonation reactions of half-sandwich iridium complexes bearing a vicinal dioxime ligand were studied. Treatment of [{Cp*IrCl(µ-Cl)}2 ] (Cp*=η5 -C5 Me5 ) with dimethylglyoxime (LH2 ) at an Ir:LH2 ratio of 1:1 afforded the cationic dioxime iridium complex [Cp*IrCl(LH2 )]Cl (1). The chlorido complex 1 undergoes stepwise and reversible deprotonation with potassium carbonate to give the oxime-oximato complex [Cp*IrCl(LH)] (2) and the anionic dioximato(2-) complex K[Cp*IrCl(L)] (3) sequentially. Meanwhile, twofold deprotonation of the sulfato complex [Cp*Ir(SO4 )(LH2 )] (4) resulted in the formation of the oximato-bridged dinuclear complex [{Cp*Ir(µ-L)}2 ] (5). X-ray analyses disclosed their supramolecular structures with one-dimensional infinite chain (1 and 2), hexagonal open channels (3), and a tetrameric rhomboid (4) featuring multiple intermolecular hydrogen bonds and electrostatic interactions.

Macrocyclic Metal Complexes Bearing Rigid Polyaromatic Ligands: Synthesis and Catalytic Activity.

We synthesised palladium and platinum complexes possessing cyclic and acyclic pincer-type polyaromatic ligands and investigated their structural effect on the catalysis. The pincer-type bis(6-arylpyridin-2-yl)benzene skeleton was constructed via Kröhnke pyridine synthesis under transition metal-free conditions on gram-scale quantity. Ligand structure significantly influenced catalytic activity toward the platinum-catalysed hydrosilylation of diphenyl acetylenes, despite the ligand-independence of the conformations and electronic properties of these complexes.

Metal-ligand cooperative C-O bond cleavage of propargylic alcohol with protic pyrazole complexes of ruthenium.

The C-O bond cleavage of a propargylic alcohol, 1,1-dimethyl-3-phenylprop-2-yn-1-ol (3), by metal-ligand cooperation was investigated. The reactions of a naphthalene complex [CpRu(η6-C10H8)]PF6 (Cp = η5-C5H5) with 5-R-3-(pyrid-2-yl)pyrazoles (R-LH; R = Ph, CF3) in acetonitrile afforded the starting metal-ligand bifunctional ruthenium complexes [CpRu(R-LH)(MeCN)]PF6 (1a, R = Ph; 1b, R = CF3) featuring an N-N chelate protic pyrazole. The treatment of the CF3-substituted pyrazole complex 1b with 3 in 1,2-dichloroethane at 50 °C resulted in the formation of the η3-butadienyl complex 5. Meanwhile, the corresponding reaction of the phenylpyrazole complex 1a in 1,4-dioxane at 90 °C gave the N-allenylmethylpyrazole complex 6. The C-O and C-H bond cleavage of 3 in these reactions can be ascribed to the metal-ligand cooperation: initial formation of an η3-propargyl complex assisted by NHO hydrogen bonding and following C-H deprotonation by the neighboring pyrazolato ligand. On the other hand, in boiling methanol, the protic pyrazole complex 1a catalyzed the C-O bond cleavage of 3, which resulted in catalytic isomerization of 3 to an α,ß-unsaturated enone, 3-methyl-1-phenylbut-2-en-1-one (8). The control experiments using non-protic and isocyanide ruthenium complexes indicated that both a labile nitrile ligand on the metal and the protic cooperating ligand are crucial for the catalysis.

Reductive Amination of Ketonic Compounds Catalyzed by Cp*Ir(III) Complexes Bearing a Picolinamidato Ligand.

Cp*Ir complexes bearing a 2-picolinamide moiety serve as effective catalysts for the direct reductive amination of ketonic compounds to give primary amines under transfer hydrogenation conditions using ammonium formate as both the nitrogen and hydrogen source. The clean and operationally simple transformation proceeds with a substrate to catalyst molar ratio (S/C) of up to 20,000 at relatively low temperature and exhibits excellent chemoselectivity toward primary amines.

Cleavage of N-H Bond of Ammonia via Metal-Ligand Cooperation Enables Rational Design of a Conceptually New Noyori-Ikariya Catalyst.

The asymmetric transfer hydrogenation (ATH) of ketones/imines with Noyori-Ikariya catalyst represents an important reaction in both academia and fine chemical industry. The method allows for the preparation of chiral secondary alcohols/amines with very good to excellent optical purities. Remarkably, the same chiral Noyori-Ikariya complex is also a precatalyst for a wide range of other chemo- and stereoselective reductive and oxidative transformations. Among them are enantioselective sulfonamidation of acrylates (intramolecular aza-Michael reaction) and carboxylation of indoles with CO2. Development of these catalytic reactions has been inspired by the realized cleavage of the N-H bond of sulfonamides and indoles by the 16e- amido derivative of the 18e- precatalyst via metal-ligand cooperation (MLC). This paper summarizes our efforts to investigate N-H bond cleavage of gaseous ammonia in solution via MLC and reports the serendipitous discovery of a new class of chiral tridentate κ3[ N, N', N″] Ru and Ir metallacycles, derivatives of the famous M-FsDPEN catalysts (M = Ru, Ir). The protonation of these metallacycles by strong acids containing weakly coordinating (chiral) anions generates ionic complexes, which were identified as conceptually novel Noyori-Ikariya precatalysts. For example, the ATH of aromatic ketones with some of these complexes proceeds with up to 99% ee.

Metallo-supramolecular assembly of protic pincer-type complexes: encapsulation of dinitrogen and carbon disulfide into a multiproton-responsive diruthenium cage.

Partial dehydrobromination of a diprotic pincer-type ruthenium complex in the presence of a rigid 1,3-bis(diphenylphosphino)benzene linker provided a dinuclear cage containing a guest template KBr surrounded by hydrogen bonds and electrostatic interactions. Dinitrogen and carbon disulfide were encapsulated into the cage with proton channels formed by the pyrazole arms in the pincer ligands.