One-Pot Synthesis of Chiral 1-Aryl-2-Aminoethanols via Ir-Catalyzed Asymmetric Hydrogenation.

A straightforward synthesis approach to chiral 1-aryl-2-aminoethanols via the one-pot asymmetric hydrogenation catalyzed by Ir catalyst was developed. This tandem process involves the in situ generation of α-amino ketones via the nucleophilic substitution of α-bromoketones with amines and the Ir-catalyzed asymmetric hydrogenation of ketone intermediates to provide diverse enantiomerically enriched ß-amino alcohols. The excellent yields and enantioselectivities (up to 96 % yield and up to >99 % ee) with a wide substrate scope in this one-pot strategy were obtained.

para-Selective, Direct C(sp2)-H Alkylation of Electron-Deficient Arenes by the Electroreduction Process.

Direct para-selective C(sp2)-H alkylation of electron-deficient arenes based on the electroreduction-enabled radical addition of alkyl bromides has been developed under mild conditions. In the absence of any metals and redox agents, the simple electrolysis system tolerates a variety of primary, secondary, and tertiary alkyl bromides and behaves as an important complement to the directed alkylation of the C(sp2)-H bond and the classic Friedel-Crafts alkylation. This electroreduction process provides a more straightforward, environmentally benign, and effective alkylation method for electron-deficient arenes.

Iridium-Catalyzed Asymmetric Hydrogenation of Simple Ketones with Tridentate PNN Ligands Bearing Unsymmetrical Vicinal Diamines.

An iridium catalytic system with a ferrocene-based phosphine ligand bearing a modular and tunable unsymmetrical vicinal diamine scaffold was developed for the asymmetric hydrogenation of aryl ketones. This approach provided a powerful tool for the enantioselective synthesis of diverse chiral alcohols with excellent reactivity and enantioselectivity (up to 99% yield, up to 99% ee, and up to 50,000 turnover number). The substituents and chirality of unsymmetrical diamines in ligands played an important role in the satisfactory results.

The Influence of the Substrate on the Functionality of Spin Crossover Molecular Materials.

Spin crossover complexes are a route toward designing molecular devices with a facile readout due to the change in conductance that accompanies the change in spin state. Because substrate effects are important for any molecular device, there are increased efforts to characterize the influence of the substrate on the spin state transition. Several classes of spin crossover molecules deposited on different types of surface, including metallic and non-metallic substrates, are comprehensively reviewed here. While some non-metallic substrates like graphite seem to be promising from experimental measurements, theoretical and experimental studies indicate that 2D semiconductor surfaces will have minimum interaction with spin crossover molecules. Most metallic substrates, such as Au and Cu, tend to suppress changes in spin state and affect the spin state switching process due to the interaction at the molecule-substrate interface that lock spin crossover molecules in a particular spin state or mixed spin state. Of course, the influence of the substrate on a spin crossover thin film depends on the molecular film thickness and perhaps the method used to deposit the molecular film.

Synthesis of Phenols from Aryl Ammonium Salts under Mild Conditions.

A general method for the synthesis of phenols from electron-deficient aryl ammonium salts or heteroaryl ammonium salts under mild conditions was developed. Benzaldehyde oxime, acetohydroxamic acid, and hydroxylamine hydrochloride were investigated as hydroxide surrogates respectively. With these hydroxide surrogates, a series of phenols were prepared in yields of 20-98%.

Synthesis of triarylphosphines from arylammonium salts via one-pot transition-metal-free C-P coupling.

A nucleophilic aromatic substitution (SNAr) reaction that allowed transition-metal-free C-P bond construction via C-N bond cleavage was developed. The coupling between aryltrimethylammonium salts and secondary phosphines from the in situ reduction of diarylphosphine oxides led to the formation of diverse triarylphosphines with various functional groups. This one-pot process was not only a pertinent SNAr precedent but also a favorable transition-metal-free alternative for C-P coupling.

Primary amine catalyzed diastereo- and enantioselective Michael reaction of thiazolones and α,ß-unsaturated ketones.

The chiral primary amine catalyzed asymmetric Michael reaction of thiazolones and α,ß-unsaturated ketones was reported. Two different optimal catalytic systems were obtained corresponding to cyclic and linear α,ß-unsaturated ketones. By employing chiral primary amines as the catalysts and amino-acid derivatives as the additives, a variety of Michael adducts containing the scaffold of the thiazole ring were prepared in moderate to good yields and with excellent diastereo- and enantioselectivities (up to 95% yield, all up to >19/1 dr, up to 96% ee). The reaction was scaled up to obtain 1.73 grams of the Michael adduct with the maintenance of yield and stereoselectivity.

Direct Arylation of α-Amino C(sp3 )-H Bonds by Convergent Paired Electrolysis.

A metal-free convergent paired electrolysis strategy to synthesize benzylic amines through direct arylation of tertiary amines and benzonitrile derivatives at room temperature has been developed. This TEMPO-mediated electrocatalytic reaction makes full use of both anodic oxidation and cathodic reduction without metals or stoichiometric oxidants, thus showing great potential and advantages for practical synthesis. This convergent paired electrolysis method provides a straightforward and powerful means to activate C-H bonds and realize cross-coupling with cathodically generated species.

Low-Density Lipoprotein Cholesterol and Prostate Cancer: A Retrospective Study.

BACKGROUND: This work aimed to investigate the potential role of abnormal lipid metabolism in the development of prostate cancer (PCa). METHODS: A retrospective study design was used. The clinical data of 520 patients who underwent rectal prostate biopsy in our hospital from January 2020 to June 2023 were analysed. The patients were enrolled and divided into the anterior PCa group including 112 patients and benign prostatic hyperplasia (BPH) group including 408 patients. Univariate and multivariate logistic regression analyses were performed for the two patient groups, and further comparisons were made according to the Gleason score and TNM staging. RESULTS: Low-density lipoprotein cholesterol (LDL-C) level may be an independent risk factor for PCa, and it was significantly associated with the risk of PCa (odds ratio (OR) = 1.363, p = 0.030). Patients with PCa were further divided into the low risk group and the high risk group according to the Gleason score. Univariate analysis (p = 0.047) and logistic regression analysis (OR = 2.249, p = 0.036) revealed that LDL-C was a significant factor influencing the Gleason score. Patients with PCa were categorised into four groups based on TNM staging. One-way analysis of variance (ANOVA) analysis (p = 0.015) and ordinal logistic regression analysis (OR = 2.414, p = 0.007) demonstrated that LDL-C was a significant factor influencing TNM staging. CONCLUSIONS: This study revealed the important role of LDL-C in the development of PCa, highlighting its influence as an independent risk factor. Thus, LDL-C may promote the proliferation and invasion of PCa cells.

Direct electrochemical synthesis of quinones from simple aromatics and heteroaromatics.

We developed an electrochemical strategy for the synthesis of quinones through direct oxidation of widely accessible arenes and heteroarenes under mild conditions. A variety of quinones and hetero quinones were prepared with moderate to good yields, without the involvement of the pre-functionalized substrates. In addition, this atom economic method also exhibits wide functional group tolerance, including C(sp2)-I bond, ester, aldehyde, and OTf groups. This synthetic approach provides a straightforward and atom economic method for the transformation of C(sp2)-H bonds.

Optical characterization of isothermal spin state switching in an Fe(II) spin crossover molecular and polymer ferroelectric bilayer.

Using optical characterization, it is evident that the spin state of the spin crossover molecular complex [Fe{H2B(pz)2}2(bipy)] (pz = tris(pyrazol-1-1y)-borohydride, bipy = 2,2'-bipyridine) depends on the electric polarization of the adjacent polymer ferroelectric polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) thin film. The role of the PVDF-HFP thin film is significant but complex. The UV-Vis spectroscopy measurements reveals that room temperature switching of the electronic structure of [Fe{H2B(pz)2}2(bipy)] molecules in bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] occurs as a function of ferroelectric polarization. The retention of voltage-controlled nonvolatile changes to the electronic structure in bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] strongly depends on the thickness of the PVDF-HFP layer. The PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] interface may affect PVDF-HFP ferroelectric polarization retention in the thin film limit.

Electronic structure of cobalt valence tautomeric molecules in different environments.

Future molecular microelectronics require the electronic conductivity of the device to be tunable without impairing the voltage control of the molecular electronic properties. This work reports the influence of an interface between a semiconducting polyaniline polymer or a polar poly-D-lysine molecular film and one of two valence tautomeric complexes, i.e., [CoIII(SQ)(Cat)(4-CN-py)2] ↔ [CoII(SQ)2(4-CN-py)2] and [CoIII(SQ)(Cat)(3-tpp)2] ↔ [CoII(SQ)2(3-tpp)2]. The electronic transitions and orbitals are identified using X-ray photoemission, X-ray absorption, inverse photoemission, and optical absorption spectroscopy measurements that are guided by density functional theory. Except for slightly modified binding energies and shifted orbital levels, the choice of the underlying substrate layer has little effect on the electronic structure. A prominent unoccupied ligand-to-metal charge transfer state exists in [CoIII(SQ)(Cat)(3-tpp)2] ↔ [CoII(SQ)2(3-tpp)2] that is virtually insensitive to the interface between the polymer and tautomeric complexes in the CoII high-spin state.

DFT functional benchmarking on the energy splitting of chromium spin states and mechanistic study of acetylene cyclotrimerization over the Phillips Cr(II)/silica catalyst.

In this work, a two-state reaction mechanism for the acetylene cyclotrimerization over a cluster model for the Phillips Cr(II)/silica catalyst were systematically investigated using density functional theory (DFT). Since spin crossover phenomenon was confirmed in the catalytic cycle, an accurate prediction of the energy gap between low- and high-spin states is crucial for the description of a reaction involving a two-state reactivity. Therefore, a massive DFT functional benchmarking test has been conducted on the cluster model by taking a CASPT2 energy gap as a reference. Consequently, B3PW91* with 28% Hartree-Fock exchange energy was selected for the following mechanistic investigation. Each of the possible potential energy surface including singlet, triplet, and quintet surfaces was explored. On the quintet surface, the reaction begins with a coordination of an acetylene on the chromium center to generate a π-coordinated complex. The following oxidative coupling through further coordination with a second acetylene was predicted to be a two-step reaction to generate a chromacyclopentadiene species. This transformation was found to be energetically prohibitive by the presence of the transition state (5)TS[C-E] (ΔG(‡) = 31.1 kcal/mol). On the triplet surface, however, the coordination of an acetylene generates a chromacyclopropene species without showing any activation barrier. The second acetylene incorporation proceeding via a coordination on the chromium center followed by an insertion into a Cr-C σ-bond of the chromacyclopropene was predicted to be a facile reaction pathway (ΔG(‡) = 10.2 kcal/mol). The third acetylene was captured by the cluster model through the formation of a hydrogen bond. The later transformation on the triplet surface was found to be an intermolecular [4 + 2] cycloaddition to finish the cyclization. The lack of the aromaticity of the benzene ring in (3)L results in an uncompleted reaction pathway on a single triplet surface. Consequently, a two-state reaction pathway that is connected by two low-lying minimum-energy crossing points (MECPs) of the two surfaces is thus described. It is worthy of note that the third acetylene in the tri(acetylene)chromium complex captured by the cluster model only through the formation of a hydrogen bond rules out the [2 + 2 + 2] concerted one-step reaction pathway proposed by Zecchina et al. [Phys. Chem. Chem. Phys.2003, 5, 4414]. The singlet reaction profile is far higher in energy compared with that proceeded on the triplet and quintet surfaces.

Rapid Synthesis of α-Chiral Piperidines via a Highly Diastereoselective Continuous Flow Protocol.

A practical continuous flow protocol has been developed using readily accessible N-(tert-butylsulfinyl)-bromoimine and Grignard reagents, providing various functionalized piperidines (34 examples) in superior results (typically >80% yield and with >90:10 dr) within minutes. The high-performance scale-up is smoothly carried out, and efficient synthesis of the drug precursor further showcases its utility. This flow process offers rapid and scalable access to enantioenriched α-substituted piperidines.

Iridium-catalyzed enantioselective synthesis of chiral γ-amino alcohols and intermediates of (S)-duloxetine, (R)-fluoxetine, and (R)-atomoxetine.

Chiral γ-amino alcohols are the prevalent structural motifs and building blocks in pharmaceuticals and bioactive molecules. Enantioselective hydrogenation of ß-amino ketones provides a straightforward and powerful tool for the synthesis of chiral γ-amino alcohols, but the asymmetric transformation is synthetically challenging. Here, a series of tridentate ferrocene-based phosphine ligands bearing modular and tunable unsymmetrical vicinal diamine scaffolds were designed, synthesized, and evaluated in the iridium-catalyzed asymmetric hydrogenation of ß-amino ketones. The system was greatly effective to substrates with flexible structure and functionality, and diverse ß-tertiary-amino ketones and ß-secondary-amino ketones were hydrogenated smoothly. The excellent reactivities and enantioselectivities were achieved in the asymmetric delivery of various chiral γ-amino alcohols with up to 99% yields, >99% ee values, and turnover number (TON) of 48,500. The gram-scale reactions with low catalyst loading showed the potential application in industrial synthesis of chiral drugs, such as (S)-duloxetine, (R)-fluoxetine, and (R)-atomoxetine.

Electricity-driven three-component reductive coupling reaction for the synthesis of diarylmethylamine.

A three-component reductive coupling reaction of aldehydes, amines and cyanopyridines under electrochemical conditions has been developed. The in situ generated imine and cyanopyridine simultaneously undergo single-electron reduction at the cathode, and afford diarylmethylamines through radical coupling without the participation of reducing agents. The one-pot electrolysis method can modularly obtain various secondary and tertiary amines and exhibits broad functional group compatibility. Mechanistic experiments verify the pivotal reduction step from imine to α-amino radical and reveal the key role of benzoic acid in reducing the reduction potential of imine and cyanopyridine.

Ritter-type amination of C(sp3)-H bonds enabled by electrochemistry with SO42.

By merging electricity with sulfate, the Ritter-type amination of C(sp3)-H bonds is developed in an undivided cell under room temperature. This method features broad substrate generality (71 examples, up to 93% yields), high functional-group compatibility, facile scalability, excellent site-selectivity and mild conditions. Common alkanes and electron-deficient alkylbenzenes are viable substrates. It also provides a straightforward protocol for incorporating C-deuterated acetylamino group into C(sp3)-H sites. Application in the synthesis or modification of pharmaceuticals or their derivatives and gram-scale synthesis demonstrate the practicability of this method. Mechanistic experiments show that sulfate radical anion, formed by electrolysis of sulfate, served as hydrogen atom transfer agent to provide alkyl radical intermediate. This method paves a convenient and flexible pathway for realizing various synthetically useful transformations of C(sp3)-H bonds mediated by sulfate radical anion generated via electrochemistry.

Intermolecular interaction and cooperativity in an Fe(II) spin crossover molecular thin film system.

Compact domain features have been observed in spin crossover [Fe{H2B(pz)2}2(bipy)] molecular thin film systems via soft x-ray absorption spectroscopy and photoemission electron microscopy. The domains are in a mixed spin state that on average corresponds to roughly 2/3 the high spin occupation of the pure high spin state. Monte Carlo simulations support the presence of intermolecular interactions that can be described in terms of an Ising model in which interactions beyond nearest-neighbors cannot be neglected. This suggests the presence of short-range order to permit interactions between molecules beyond nearest neighbor that contribute to the formation of largely high spin state domains structure. The formation of a spin state domain structure appears to be the result of extensive cooperative effects.

Evidence of dynamical effects and critical field in a cobalt spin crossover complex.

The [Co(SQ)2(4-CN-py)2] complex exhibits dynamical effects over a wide range of temperature. The orbital moment, determined by X-ray magnetic circular dichroism (XMCD) with decreasing applied magnetic field, indicates a nonzero critical field for net alignment of magnetic moments, an effect not seen with the spin moment of [Co(SQ)2(4-CN-py)2].

DFT and CASPT2 study on the mechanism of ethylene dimerization over Cr(II)OH+ cation.

In this work, the ethylene coordination and dimerization mechanism over Cr(II)OH(+) cation were systematically investigated using density functional theory (DFT) and complete active space second-order perturbation theory (CASPT2). It was found that Cr(II)OH(+) cation can coordinate with up to four ethylene molecules which gives seven possible stable Cr(II)OH(+)·(C(2)H(4))(n) (n = 1-4) π-complexes. We investigated whether ethylene dimerization over Cr(II)OH(+) cation proceeds through either a carbene mechanism or a metallacycle mechanism. The potential energy surfaces were characterized using four different functionals (M06L, BLYP, B3LYP, and M06). It was found that the potential energy profiles calculated at the M06 level agreed well with the CASPT2 energy profiles. Since the intermediates involved in the proposed catalytic cycles showed different ground spin states, a reaction pathway involving a spin crossing between two potential energy surfaces was observed. The minimum-energy crossing points (MECPs) that connect the two potential energy surfaces were successfully located. The two-state metallacycle reaction pathway with the formation of chromacyclopentane as the rate-determining step was found to be energetically more favorable than the carbene reaction pathway. 1-Butene was formed from the chromacyclopentane by a two-step reductive elimination pathway through a chromium(IV) hydride intermediate.