Ligand Relay Catalysis Enables Asymmetric Migratory Hydroarylation for the Concise Synthesis of Chiral α-(Hetero)Aryl-Substituted Amines.

Complementary to the design of a single structurally complex chiral ligand to promote each step in transition-metal catalysis, multiligand relay catalysis through dynamic ligand exchange with each step in the catalytic cycle promoted by its best ligand provides an attractive approach to enhance the whole reaction reactivity and selectivity. Herein, a regio- and enantioselective NiH-catalyzed migratory hydroarylation process with a simple combination of a chain-walking ligand and an asymmetric arylation ligand, producing high-value chiral α-(hetero)aryl-substituted amines and their derivatives under mild conditions, is reported. The potential synthetic applications of this transformation are demonstrated by the concise synthesis of (S)-nicotine and a CDK8 inhibitor.

Nickel-Catalyzed Migratory Cross-Coupling Reactions: New Opportunities for Selective C-H Functionalization.

ConspectusMigratory cross-coupling via metal migration is a process of significant academic and industrial interest. It provides an attractive alternative for the selective installation of a functional group at remote C-H positions from simple precursors, thus enabling the direct synthesis of challenging structures not accessible with traditional cross-coupling. In particular, with the merger of 1,n-Ni/H shift and cross-coupling of nickel, the Ni-catalyzed migratory functionalization of simple precursors has undergone particularly intense development and emerged as a valuable field of research in the past few years. This Account will outline the recent progress made in this arena in terms of migration-functionalization modes, diverse functionalizations, and strategies for regio- and stereocontrol. Mechanistic studies and synthetic applications are also discussed.In detail, we systematically categorize our work into two parts based on the migration modes. In the first part, a platform is created for Ni-catalyzed migratory sp3 C-H functionalization of alkenes or alkyl halides via iterative 1,2-Ni/H shift-selective cross-coupling. The key reactive Ni(II)H species for chain-walking could be generated in situ either in a polarity-reversed fashion relying on stoichiometric reductants (X-Ni(II)-H) or in a redox-neutral fashion with the participation of nucleophilic coupling partners (FG-Ni(II)-H). One significant advantage associated with the polarity-reversed NiH system is the use of relatively stable, abundant, and safe olefin surrogates or alkyl halides instead of the sensitive organometallics required in traditional cross-coupling reactions. Another advantage is that diverse functionalizations, including carbonation and more challenging amination and thiolation could be smoothly achieved with suitable electrophiles or their precursors. Finally, to address the challenging multifaceted selectivity and reactivity issues in asymmetric migratory cross-coupling reactions, we have developed a feasible ligand relay catalytic strategy. In this dynamic ligand exchange process, one ligand promotes rapid migration while the other promotes highly regio- and stereoselective coupling. This innovative strategy overcomes the formidable challenge stemming from the difficulty of designing a single ligand to efficiently promote both steps of chain-walking and asymmetric coupling. In the second part, a new platform for Ni-catalyzed migratory sp2 C-H functionalization via 1,4-Ni/H shift-selective cross-coupling has been reported. Starting from readily available aryl or vinyl coupling partners, the in situ-generated aryl- or vinylnickel(II) species could undergo a rapid and reversible 1,4-Ni/H shift along an sp2 backbone, and subsequent selective coupling with various coupling partners would allow regio- and stereoselective access to diverse 1,4-migratory functionalization products. The key to success was the discovery of an appropriate ligand to efficiently promote both migration and subsequent selective cross-coupling. A vinyl-to-aryl 1,4-Ni/H shift successfully enables the modular ipso/ortho difunctionalization of aryl coupling partners, while an aryl-to-vinyl 1,4-Ni/H shift enables regio- and stereoselective access to functionalized trisubstituted alkenes.We hope that this Account will inspire broad interest and future development of migratory cross-coupling reactions. We strongly believe that continued efforts in this fascinating field will overcome many of the remaining challenges, including cutting-edge ligand/catalyst design to enhance reactivity and selectivity, conceptually new migration modes for additional transformations, and in-depth mechanistic studies for rational reaction design.

High Performance On-Chip Energy Storage Capacitors with Plasma-Enhanced Atomic Layer-Deposited Hf0.5Zr0.5O2/Al-Doped Hf0.25Zr0.75O2 Nanofilms as Dielectrics.

Concurrently achieving high energy storage density (ESD) and efficiency has always been a big challenge for electrostatic energy storage capacitors. In this study, we successfully fabricate high-performance energy storage capacitors by using antiferroelectric (AFE) Al-doped Hf0.25Zr0.75O2 (HfZrO:Al) dielectrics together with an ultrathin (1 nm) Hf0.5Zr0.5O2 underlying layer. By optimizing the Al concentration in the AFE layer with the help of accurate controllability of the atomic layer deposition technique, an ultrahigh ESD of 81.4 J cm-3 and a perfect energy storage efficiency (ESE) of 82.9% are simultaneously achieved for the first time in the case of the Al/(Hf + Zr) ratio of 1/16. Meanwhile, both the ESD and ESE exhibit excellent electric field cycling endurance within 109 cycles under 5~5.5 MV cm-1, and robust thermal stability up to 200 °C. Thus, the fabricated capacitor is very promising for on-chip energy storage applications due to favorable integratability with the standard complementary metal-oxide-semiconductor (CMOS) process.

Functionalization of Olefinic C-H Bonds by an Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Coupling Sequence.

An attractive approach to selective functionalization of remote C-H bonds is a metal/hydride shift/cross-coupling reaction sequence. Complimentary to the heavily exploited 1,2-nickel/hydride shift along an sp3 chain, a chain-walking process, the 1,4-nickel/hydride shift along an sp2 chain is more complex. Here we report an unprecedented aryl-to-vinyl 1,4-nickel/hydride shift reaction, in which the migratory alkenylnickel species generated in situ is selectively trapped by one of various coupling partners, such as isocyanates, alkyl bromides, aryl chlorides or alkynyl bromides, allowing regio- and stereoselective access to trisubstituted alkenes. In contrast to the well-reported ipso-aryl coupling reactions, this strategy provides remote alkenyl C-H functionalized products with good yield and with excellent chemo-, regio- and E/Z-selectivity.

Analysis of factors associated with 6MWD among older patients with chronic heart failure.

OBJECTIVES: To study the factors that influence the 6-minute walking distance (6MWD) among older patients with chronic heart failure. METHODS: This was a single-center, retrospective, observational study. A total of 123 patients from the First Affiliated Hospital of Nanjing Medical University was selected. The factors associated with the 6MWD were analyzed using Pearson correlation analysis and multivariate linear regression. RESULTS: The 6MWD of older patients was negatively correlated with age, fall risk, nutritional score, frailty, and depression but was positively correlated with educational level, fall efficacy, self-care ability, and plasma albumin. The results of independent variable multiple linear regression analysis showed that age (ß = -0.098), fall risk (ß = -0.262), fall efficacy (ß = 0.011), self-care ability (ß = -0.021), nutrition (ß = -0.405), frailty (ß = -0.653), and plasma albumin (ß = 0.127) influenced the 6MWD. CONCLUSIONS: The 6MWD of older patients with chronic heart failure was related to age, self-care ability, fall risk, nutrition, frailty, and depression.

Superhigh energy storage density on-chip capacitors with ferroelectric Hf0.5Zr0.5O2/antiferroelectric Hf0.25Zr0.75O2 bilayer nanofilms fabricated by plasma-enhanced atomic layer deposition.

Thanks to their excellent compatibility with the complementary metal-oxide-semiconductor (CMOS) process, antiferroelectric (AFE) HfO2/ZrO2-based thin films have emerged as potential candidates for high-performance on-chip energy storage capacitors of miniaturized energy-autonomous systems. However, increasing the energy storage density (ESD) of capacitors has been a great challenge. In this work, we propose the fabrication of ferroelectric (FE) Hf0.5Zr0.5O2/AFE Hf0.25Zr0.75O2 bilayer nanofilms by plasma-enhanced atomic layer deposition for high ESD capacitors with TiN electrodes. The effects of the FE/AFE thickness composition and annealing conditions are investigated, revealing that the Hf0.5Zr0.5O2 (1 nm)/Hf0.25Zr0.75O2 (9 nm) bilayer can generate the optimal ESD after optimized annealing at 450 °C for 30 min. This is mainly ascribed to the factor that the introduction of a 1 nm Hf0.5Zr0.5O2 layer enhances the formation of the tetragonal (T) phase with antiferroelectricity in the AFE Hf0.25Zr0.75O2 layer as well as the breakdown electric field of the bilayer while fixing the FE/AFE bilayer thickness at 10 nm. As a result, a ESD as high as 71.95 J cm-3 can be obtained together with an energy storage efficiency (ESE) of 57.8%. Meanwhile, with increasing the measurement temperature from 300 and 425 K, the capacitor also demonstrates excellent stabilities of ESD and ESE. In addition, superior electrical cycling endurance is also demonstrated. Further, by integrating the capacitor into deep silicon trenches, a superhigh ESD of 364.1 J cm-3 is achieved together with an ESE of 56.5%. This work provides an effective way for developing CMOS process-compatible, eco-friendly and superhigh ESD three-dimensional capacitors for on-chip energy storage applications.

NiH-Catalyzed Functionalization of Remote and Proximal Olefins: New Reactions and Innovative Strategies.

Transition metal hydride catalyzed functionalization of remote and proximal olefins has many advantages over conventional cross-coupling reactions. It avoids the separate, prior generation of stoichiometric amounts of organometallic reagents and the use of preformed organometallic reagents, which are sometimes hard to access and may compromise functional group compatibility. The migratory insertion of metal hydride complexes generated in situ into readily available alkene starting materials, the hydrometalation process, provides an attractive and straightforward route to alkyl metal intermediates, which can undergo a variety of sequential cross-coupling reactions. In particular, with the synergistic combination of chain-walking and cross-coupling chemistry of nickel, NiH-catalyzed functionalization of remote and proximal olefins has undergone particularly intense development in the past few years. This Account aims to chronicle the progress made in this arena in terms of activation modes, diverse functionalizations, and chemo-, regio-, and enantioselectivity.We first provide a brief introduction to the general reaction mechanisms. Taking remote hydroarylation as an example, the four oxidation states of Ni have allowed us to develop two different reaction strategies to form the final product: a Ni(I)-H/X-Ni(II)-H platform that relies on stoichiometric reductants and a Ni(I/II/III) cycle and a redox-neutral functional group or FG-Ni(II)-H platform that reacts with an alkene substrate and forms the migratory products via a Ni(0/II) pathway. We also demonstrate that diverse functionalization, including general C-C bond-forming reactions and the more challenging C-N/C-S bond-forming reactions could be realized. Moreover, the employment of appropriate chiral ligands has allowed us to successfully realize the corresponding asymmetric hydrofunctionalization reactions of olefins, including hydroalkylation, hydroarylation, hydroalkenylation, hydroalkynylation, and hydroamination. Interestingly, the enantio-determining step could be enantioselective hydronickelation, selective oxidative addition, or selective reductive elimination. To realize more challenging asymmetric migratory hydrofunctionalization, we have developed a general ligand relay catalytic strategy with a combination of two simple ligands, the first for chain-walking and the second for asymmetric coupling. This novel strategy avoids the design of a single, possibly structurally complex chiral ligand to promote both steps of chain-walking and asymmetric coupling. In addition, the success of multicomponent hydrofunctionalization provides a convenient approach to gain simple access to complex molecules. Finally, alkyl halides could be used as olefin precursors to undergo a variety of reductive migratory cross-electrophile coupling reactions. Applications of these remote hydrofunctionalization reactions are also discussed. We hope this Account will inspire future development in the field to overcome key challenges, including conceptually new catalytic strategies, development of high-performance systems with enhanced reactivity and selectivity, cutting-edge catalyst design, and further mechanistic studies.

Regio- and enantioselective remote hydroarylation using a ligand-relay strategy.

The design of a single complicated chiral ligand to well-promote each step of an asymmetric cascade reaction is sometimes a formidable challenge in transition metal catalysis. In this work, a highly regio- and enantioselective Ni-catalysed migratory hydroarylation relay process has been achieved with the combination of two simple ligands, one which accomplishes chain-walking and the other causing asymmetric arylation. This formal asymmetric C(sp3)-H arylation provides direct access to a wide range of structurally diverse chiral 1,1-diarylalkanes, a structural unit found in a number of bioactive molecules. The value of this strategy was further demonstrated by the Ni-catalysed migratory asymmetric 1,3-arylboration.

Design of the modified fractional central difference Kalman filters under stochastic colored noises.

For state estimation of discrete nonlinear fractional stochastic systems, this study presents two innovative modified fractional central difference Kalman filters. We consider a complicated scenario where the process noise or measurement noise in the system become colored noise. Firstly, the nonlinear function is linearized by utilizing the Stirling polynomial interpolation formula. Thus there is no need to calculate the Jacobi matrix for both algorithms, which means very few application limitations. Then, based on the augmented-state method, we develop an augmented state fractional central difference Kalman filter under the scenario of colored process noise. Afterwards, a state estimation algorithm for handling stochastic systems containing colored measurement noise is put forward by using the measurement expansion method. Finally, to perform the superiority of the developed algorithms, several simulations are carried out. As well, the algorithms derived in this paper are contrasted with the original fractional central difference Kalman filter and three other algorithms. Notably, a simulation with engineering significance for the state-of-charge estimation for lithium-ion batteries is also introduced, Aside from the commonly used numerical simulation. The results verify the superiority of the developed algorithms in sense of estimation accuracy and real-time performance.

Nickel-Catalyzed Ipso/Ortho Difunctionalization of Aryl Bromides with Alkynes and Alkyl Bromides via a Vinyl-to-Aryl 1,4-Hydride Shift.

Polysubstituted arenes are ubiquitous structures in a myriad of medicinal agents and complex molecules. Herein, we report a new catalytic blueprint that merges the modularity of nickel catalysis for bond formation with the ability to enable a rather elusive 1,4-hydride shift at arene sp2 C-H sites, thus allowing access to ipso/ortho-difunctionalized arenes from readily available aryl halides under mild conditions and exquisite selectivity profile.

NiH-catalyzed asymmetric hydroarylation of N-acyl enamines to chiral benzylamines.

Enantiomerically pure chiral amines and related amide derivatives are privilege motifs in many pharmacologically active molecules. In comparison to the well-established hydroamination, the transition metal-catalysed asymmetric hydrofunctionalization of enamines provides a complementary approach for their construction. Here we report a NiH-catalysed enantio- and regioselective reductive hydroarylation of N-acyl enamines, allowing for the practical access to a broad range of structurally diverse, enantioenriched benzylamines under mild, operationally simple reaction conditions.

Spatial differentiation of gully clusters based on the regional scale: an example from northeastern China.

Gully erosion represents a serious environmental threat around the world, but their spatial distribution law are unclear at the regional scale. To quantitatively characterize the spatial distribution model of gullies and determine the regularity of regional differentiation, this paper used spatial analyst and statistics method to study the spatial distribution of gullies in 34 sample areas of northeastern China based on interpretations of high-resolution remote sensing images. The results showed that the kernel density could quantitatively describe the continuous spatial clustering of gullies. Gullies in northeastern China had the characteristics of a spatially unbalanced distribution at the scale of the sample area. The average kernel density of the 34 sample areas (Moran's I was 0.43, P¡0.01P < 0.01) also indicated clustering distribution at the regional scale. The horizontal clustering characteristics of gullies exhibited an azonal distribution of being low values in the middle plain and high values on the three mountainous areas. The average kernel density in the southeastern part of the study area was highest (maximum value of 2.38). In the vertical direction, gullies were relatively undeveloped in low- and high-altitude areas, while middle-altitude areas were beneficial to the development of gullies. The effect of height differences on gully development was more significant than altitude. As the height difference increased, gullies tended to be more clustered, which can be expressed by a power function. The results of this study will not only help to understand the regional differentiation characteristics of gullies but will also provide a scientific reference for the study of spatial distribution of gullies in future.

Enantio- and Regioselective NiH-Catalyzed Reductive Hydroarylation of Vinylarenes with Aryl Iodides.

A highly enantio- and regioselective hydroarylation process of vinylarenes with aryl halides has been developed using a NiH catalyst and a new chiral bis imidazoline ligand. A broad range of structurally diverse, enantioenriched 1,1-diarylalkanes, a structure found in a number of biologically active molecules, have been obtained with excellent yields and enantioselectivities under extremely mild conditions.

Ligand-Enabled Nickel-Catalyzed Redox-Relay Migratory Hydroarylation of Alkenes with Arylborons.

A redox-relay migratory hydroarylation of isomeric mixtures of olefins with arylboronic acids catalyzed by nickel complexes bearing diamine ligands is described. A range of structurally diverse 1,1-diarylalkanes, including those containing a 1,1-diarylated quaternary carbon, were obtained in excellent yields and with high regioselectivity. Preliminary experimental evidence supports the proposed non-dissociated chainwalking of aryl-nickel(II)-hydride species along the alkyl chain of alkenes before selective reductive elimination at a benzylic position. A catalyst loading as low as 0.5 mol % proved to be sufficient in large-scale synthesis while retaining high reactivity, highlighting the practical value of this transformation.

NiH-Catalyzed Migratory Defluorinative Olefin Cross-Coupling: Trifluoromethyl-Substituted Alkenes as Acceptor Olefins to Form gem-Difluoroalkenes.

We report a NiH-catalyzed migratory defluorinative coupling between two electronically differentiated olefins. A broad range of unactivated donor olefins can be joined directly to acceptor olefins containing an electron-deficient trifluoromethyl substituent in both intra- and intermolecular fashion to form gem-difluoroalkenes. This migratory coupling shows both site- and chemoselectivity under mild conditions, with the formation of a tertiary or quaternary carbon center.

Remote Migratory Cross-Electrophile Coupling and Olefin Hydroarylation Reactions Enabled by in Situ Generation of NiH.

A highly efficient strategy for remote reductive cross-electrophile coupling has been developed through the ligand-controlled nickel migration/arylation. This general protocol allows the use of abundant and bench-stable alkyl bromides and aryl bromides for the synthesis of a wide range of structurally diverse 1,1-diarylalkanes in excellent yields and high regioselectivities under mild conditions. We also demonstrated that alkyl bromide could be replaced by the proposed olefin intermediate while using n-propyl bromide/Mn0 as a potential hydride source.

Mild and Regioselective Benzylic C-H Functionalization: Ni-Catalyzed Reductive Arylation of Remote and Proximal Olefins.

The synergistic combination of NiH-catalyzed alkene isomerization with nickel-catalyzed cross-coupling has yielded a general protocol for the synthesis of a wide range of structurally diverse 1,1-diarylalkanes in excellent yields and high regioselectivities from readily accessible olefin starting materials. Furthermore, the practicality and synthetic flexibility of this approach is highlighted by the successful employment of isomeric mixtures of olefins for regioconvergent arylation.

Asymmetric chlorination of 4-substituted pyrazolones catalyzed by natural cinchona alkaloid.

A natural quinidine-catalyzed asymmetric chlorination of 4-substituted pyrazolones is developed, affording products with a quaternary chiral chlorine-attached carbon centre in high yield with excellent enantioselectivity. The low catalyst loading (1 mol%), broad substrate scope, and facile and valuable transformation of the product highlight the practical utility of this process.

An Organocatalytic Asymmetric Friedel-Crafts Addition/Fluorination Sequence: Construction of Oxindole-Pyrazolone Conjugates Bearing Vicinal Tetrasubstituted Stereocenters.

A highly efficient and practical one-pot sequential process, consisting of an organocatalytic enantioselective Friedel-Crafts-type addition of 4-nonsubstituted pyrazolones to isatin-derived N-Boc ketimines and a subsequent diastereoselective fluorination of the pyrazolone moiety, is developed. This reaction sequence delivers novel oxindole-pyrazolone adducts featuring vicinal tetrasubstituted stereocenters with a 0.5 mol % catalyst loading in high yield with excellent enantio- and diastereocontrol. Notably, chloro, bromo, and thioether functionalities can be readily incorporated, rendering a broad diversity of the product.