Electrophilic fluoroalkylthiolation induced diastereoselective and stereospecific 1,2-metalate migration of alkenylboronate complexes

A transition metal free process for conjunctive functionalization of alkenylboron ate-complexes with electrophilic fluoroalkylthiolating reagents is described, affording β-trifluoroalkylthiolated and difluoroalkylthiolated boronic esters in good yield and excellent diastereoselectivity. The potential applicability of the method was demonstrated by the preparation of a difluoromethylthiolated mimic 12 of a potential drug molecule PF-4191834 for the treatment of asthma.

A transition metal free process for conjunctive functionalization of alkenylboron ate-complexes with electrophilic fluoroalkylthiolating reagents affords β-tri- and difluoroalkylthiolated boronic esters in good yield and diastereoselectivity.

An electrophile-induced 1,2-metalate migration of an alkenylboron “ate” complex and subsequent base-promoted β-elimination to form a functionalized cis-alkene, now the so-called Zweifel reaction, was first reported by Zweifel and co-workers in 1967 (Fig. 1A).^1–3 The reaction was proposed to proceed via an initial attack of the π electron of the alkene moiety to iodine to generate a zwitterionic iodonium ion, which then undergoes a stereospecific 1,2-metalate to afford a β-iodoboronic ester, followed by anti-elimination upon treatment with a base to afford a cis-olefin. Thus, if the iodine is replaced by an alternative electrophilic reagent and the use of a base is omitted, an interrupted-Zweifel reaction for the preparation of a stereospecific β-functionalized boronic ester could be realized. Toward this end, Aggarwal reported the first example of such a reaction by employing PhSeCl as the electrophilic reagent.⁴ It was proposed that PhSeCl first reacts with an alkenylboronate complex to form a zwitterionic seleniranium ion. Subsequent diastereospecific 1,2-metalate migration affords the stereospecific β-seleno-alkylboronate (Fig. 1B). Likewise, shortly after, Denmark and co-workers reported an analogous Lewis-base catalysed enantioselective and diastereoselective carbosulfenylation of an alkenylboronate complex using N-arylthiosaccharin as the electrophile (Fig. 1C).⁵Open in a separate windowFig. 1The interrupted Zweifel reaction.In light of these discoveries and our recent success in the development of a toolbox of electrophilic fluoroalkylthiolating reagents including three trifluoromethylthiolating reagents α-cumyltrifluoromethane sulfenate,⁶N-trifluoromethylthio-saccharin⁷ and N-trifluoromethylthiodibenzenesulfonimide,⁸ and two difluoromethylthiolating reagents N-difluoromethylthiophthalimide⁹ and S-(difluoromethyl)benzenesulfonothioate,¹⁰ we wondered whether these electrophilic fluoroalkylthiolating reagents could also trigger the proposed stereospecific 1,2-metalatation of the alkenylboronate complex to afford β-fluoroalkylthiolated borane derivatives (Fig. 1D). The trifluoromethylthio (–SCF₃) and the difluoromethylthio (–SCF₂H) groups have gained great attention recently, partially because of their high and tuneable lipophilicity¹¹ that might improve the drug candidate''s cell membrane permeability and consequently, its overall pharmacokinetics.¹² Thus, the development of new efficient reactions for the incorporation of the trifluoromethylthio¹³ or difluoromethylthio groups¹⁴ would be of vital importance in facilitating medicinal chemists'' endeavours in new drug discovery. Herein, we report that by employing electrophilic difluoromethylthiolating reagent PhSO₂SCF₂H 2a as the electrophile, the proposed difluoromethylthiolating induced stereospecific 1,2-metalate migration of alkenyl boronate complexes occurred smoothly to afford β-difluoromethylthiolated boronic esters in good yields and excellent diastereoselectivity. Likewise, when electrophilic trifluoromethylthiolating reagent N-trifluoromethylthiosaccharin 7 was used, an analogous reaction for the diastereoselective formation of β-trifluoromethylthiolated boronic esters was successfully achieved.We began our study by examining the reaction of the electrophilic difluoromethylthiolating reagent 2a with the alkenylboronate complex which was generated in situ by mixing 1a and PhLi in diethyl ether. It was found that the reaction in CH₃CN occurred in full conversion after 12 hours at room temperature, affording the corresponding product 3a in 53% yield (Table 1, entry 1). When the amount of PhLi was increased to 1.3 equivalents, the yield was increased to 76%, while the yield decreased to 66% when 2.0 equivalents of PhLi were used, likely due to the decomposition of the product under strong basic conditions (Table 1, entries 1–5). We then further investigated the effect of the reaction temperature and the solvent. It was found that the temperature did not affect the reaction significantly since the yields of the desired products were decreased slightly to 72% and 70%, respectively, when the reactions were conducted at 0 °C or −15 °C (Table 1, entries 6 and 7). Likewise, the reaction was not sensitive to the polarity of the solvent since reactions conducted in less polar solvents such as THF or CH₂Cl₂ or nonpolar solvents like toluene occurred in slightly lower 60–73% yields (Table 1, entries 9–11). We also found that reaction using N-difluoromethylthiophthalimide as the electrophilic difluoromethylthiolating reagent gave the same product in a slightly lower yield (Table 1, entry 8).Optimization of conditions for the reaction of the alkenyl boronate complex with PhSO₂SCF₂H^a

A periodic DFT study on adsorption of small molecules(CH4,CO,H2O,H2S,NH3)on the WO3(001) surface-supported Au

Gas molecules(such as CH4,CO,H2O,H2S,NH_3)adsorption on the pure and Au-doped WO3(001)surface have been studied by Density functional theory calculations with generalized gradient approximation.Based on the the calculation of adsorption energy,we found the most stable adsorption site for gas molecules by comparing the adsorption energies of different gas molecules on the WO3(001)surface.We have also compared the adsorption energy of five different gas molecules on the WO3(001)surface,our calculation results show that when the five kinds of gases are adsorbed on the pure WO3(001)surface,the order of the surface adsorption energy is CO>H2S>CH4>H2O>NH3.And the results show that NH3 is the most easily adsorbed gas among the other four gases adsorbed on the surface of pure WO3(001)surface.We also calculated the five different gases on the Au-doped WO3(001)surface.The order of adsorption energy was found to be different from the previous calculation:CO>CH4>H2S>H2O>NH3.These results provide a new route for the potential applications of Au-doped WO3 in gas molecules adsorption.     

基于U-Net的盐体识别方法

卷积神经网络在计算机视觉领域取得重大突破，利用其强大的图像处理能力，将地下沉积盐体的识别问题转化为图像语义分割问题，应用深度卷积神经网络实现盐体地震图像的像素级语义分割.本文在U-Net基础上，增加网络深度并同时引入批归一化和Dropout处理，使得神经网络模型具有更高的可信度和更强的泛化能力.通过实验发现，在卷积层之后引入批归一化处理，并在池化层和叠加层之后引入Dropout可以稳定提升模型对盐体图像的分割性能.     

缺中子Np新核素的α衰变研究

合成远离稳定线的新核素、探索原子核存在的极限是目前核物理研究的重要课题。在中子壳N=126的最丰质子一侧，极端缺中子的超铀核素处于质子滴线和中子壳的交叉位置，合成和研究该核区核素对研究N=126壳结构的演化性质具有重要意义。基于兰州重离子加速器上的充气反冲核谱仪装置(SHANS)，利用36,40Ar+185,187Re熔合蒸发反应，合成了极缺中子的219,220,223,224Np新核素，在中子壳N=126附近首次建立了Np同位素链的$ \alpha$衰变系统性，获得了N=126壳效应在Np同位素链中依然存在的实验证据。依据单质子分离能的系统性分析，确定了Np同位素链中质子滴线的位置，219Np也成为目前已知的最重的质子滴线外核素。此外，基于实验测量的反应截面，并与理论模型的计算结果相比较，讨论了进一步合成该核区其它新核素218,221,222Np的可行性。     

Preparation of pillared layered antimony hydroxide and its flame retardancy in thermoplastic polyurethane

Journal of Thermal Analysis and Calorimetry - In this article, a pillared layered antimony hydroxide (Sb-LH) material has been prepared by the hydrothermal method. X-ray diffraction,...     

Design of diamond-shape photonic crystal fiber polarization filter based on surface plasma resonance effect

A novel plasmonic polarization filter based on the diamond-shape photonic crystal fiber(PCF) is proposed. The resonant coupling characteristics of the PCF polarization filter are investigated by the full-vector finite-element method. By optimizing the geometric parameters of the PCF, when the fiber length is 5 mm, the polarization filter has a bandwidth of 990 nm and an extinction ratio(ER) of lower than -20 dB. Moreover, a single wavelength polarization filter can also be achieved, along with an ER of -279.78 dB at wavelength 1.55 μm. It is believed that the proposed PCF polarization filter will be very useful in laser and optical communication systems.     

Visible-Light-Induced Vicinal Dichlorination of Alkenes through LMCT Excitation of CuCl2

This work demonstrates photoredox vicinal dichlorination of alkenes, based on the homolysis of CuCl₂ in response to irradiation with visible light. This catalysis proceeds via a ligand to metal charge transfer process and provides an exciting opportunity for the synthesis of 1,2-dichloride compounds using an inexpensive, low-molecular-weight chlorine source. This new process exhibits a wide substrate scope, excellent functional group tolerance, extraordinarily mild conditions and does not require external ligands. Mechanistic studies show that the ready formation of chlorine atom radicals is responsible for the facile formation of C−Cl bonds in this synthetic process.     

(NH4)Bi2(IO3)2F5: An Unusual Ammonium-Containing Metal Iodate Fluoride Showing Strong Second Harmonic Generation Response and Thermochromic Behavior

An ammonium-containing metal iodate fluoride compound, (NH₄)Bi₂(IO₃)₂F₅, featuring a two-dimensional double-layered framework constructed by [BiO₂F₅]⁶⁻ and [BiO₄F₄]⁹⁻ polyhedra, as well as [IO₃]⁻ groups, was successfully synthesized. The well-ordered alignment of these SHG-active units leads to an extraordinary strong SHG response of 9.2 times that of KDP. Moreover, this compound possesses a large birefringence (Δn=0.0690 at 589.3 nm), a wide energy band gap (E_g=3.88 eV), and a high laser damage threshold (LDT; 40.2×AgGaS₂). In particular, thermochromic behavior was observed for the first time in this type of compound. Such multifunctional crystals will expand the application of nonlinear optical materials.