Catalytic asymmetric synthesis of secondary nitriles via stereoconvergent Negishi arylations and alkenylations of racemic α-bromonitriles

The first method for the stereoconvergent cross-coupling of racemic α-halonitriles is described, specifically, nickel-catalyzed Negishi arylations and alkenylations that furnish an array of enantioenriched α-arylnitriles and allylic nitriles, respectively. Noteworthy features of this investigation include: the highly enantioselective synthesis of α-alkyl-α-aryl nitriles that bear secondary α-alkyl substituents; the first examples of the use of alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl electrophiles; demonstration of the utility of a new family of ligands for asymmetric Negishi cross-couplings (a bidentate bis(oxazoline), rather than a tridentate pybox); in the case of arylzinc reagents, carbon–carbon bond formation at a remarkably low temperature (−78 °C), the lowest reported to date for an enantioselective cross-coupling of an alkyl electrophile; a mechanistic dichotomy between Negishi reactions of an unactivated versus an activated secondary alkyl bromide

Transition metal–catalyzed alkyl-alkyl bond formation: Another dimension in cross-coupling chemistry

BACKGROUND: The development of useful new methods for the construction of carbon-carbon bonds has had an impact on the many scientific disciplines (including materials science, biology, and chemistry) that use organic compounds. Tremendous progress has been made in the past several decades in the creation of bonds between sp^2-hybridized carbons (e.g., aryl-aryl bonds), particularly through the use of transition metal catalysis. In contrast, until recently, advances in the development of general methods that form bonds between sp^3-hybridized carbons (alkyl-alkyl bonds) had been rather limited. A variety of approaches, such as classical S_N^2 reactions and transition metal catalysis, typically led to side reactions rather than the desired carbon-carbon bond formation. With transition metal catalysis, the unwanted but often facile β-hydride elimination of alkylmetal complexes presented a key impediment to efficient cross-coupling of alkyl electrophiles. In the case of many alkyl-alkyl bonds, there is an additional challenge beyond construction of the carbon-carbon bond itself: controlling the stereochemistry at one or both carbons of the new bond. It is important to control the stereochemistry of organic molecules because of its influence on properties such as biological activity. Each of these two challenges is difficult to solve individually; addressing them simultaneously is even more demanding. Until recently, the methods for achieving alkyl-alkyl bond formation were comparatively limited in scope, typically involving the use of unhindered (e.g., primary) electrophiles and unhindered, highly reactive nucleophiles (e.g., Grignard reagents, which have relatively poor functional group compatibility). With respect to enantioconvergent reactions, there were virtually no examples. ADVANCES: In recent years, it has been established that, through the action of an appropriate transition metal catalyst, it is possible to achieve a broad range of alkyl-alkyl bond-forming processes; nickel-based catalysts have proved to be especially effective. With respect to the electrophilic coupling partner, a wide range of secondary alkyl halides are now suitable. This has enabled the development of enantioconvergent reactions of readily available racemic secondary electrophiles. In view of the abundance of tertiary stereocenters in organic molecules, this is a noteworthy advance in synthesis. With respect to the nucleophilic partner, alkylboron and alkylzinc reagents (Suzuki- and Negishi-type reactions, respectively) can now be used in a wide variety of alkyl-alkyl couplings, which greatly increases the utility of such processes, as these nucleophiles are more readily available and have much improved functional group compatibility relative to Grignard reagents. These new methods for alkyl-alkyl bond formation have been applied to the synthesis of natural products and other bioactive compounds. OUTLOOK: A number of major challenges remain. For example, with regard to the electrophilic coupling partner, there is a need to develop general methods that are effective for tertiary alkyl halides, including enantioconvergent processes. With regard to the nucleophilic partner, there is a need to discover more versatile catalysts that can use a wide range of hindered (e.g., secondary and tertiary) alkylmetal reagents, as well as to achieve a broad spectrum of enantioconvergent couplings of racemic nucleophiles. These advances can enable the doubly stereoconvergent coupling of a racemic electrophile with a racemic nucleophile. The synthesis of alkyl-alkyl bonds is arguably the most important bond construction in organic synthesis. The ability to achieve this bond formation at will, as well as to control the product stereochemistry, would transform organic synthesis and empower the many scientists who use organic molecules. Recent work has provided evidence that transition metal catalysis can address this exciting challenge

New time-scale criteria for model simplification of bio-reaction systems

<p>Abstract</p> <p>Background</p> <p>Quasi-steady state approximation (QSSA) based on time-scale analysis is known to be an effective method for simplifying metabolic reaction system, but the conventional analysis becomes time-consuming and tedious when the system is large. Although there are automatic methods, they are based on eigenvalue calculations of the Jacobian matrix and on linear transformations, which have a high computation cost. A more efficient estimation approach is necessary for complex systems.</p> <p>Results</p> <p>This work derived new time-scale factor by focusing on the problem structure. By mathematically reasoning the balancing behavior of fast species, new time-scale criteria were derived with a simple expression that uses the Jacobian matrix directly. The algorithm requires no linear transformation or decomposition of the Jacobian matrix, which has been an essential part for previous automatic time-scaling methods. Furthermore, the proposed scale factor is estimated locally. Therefore, an iterative procedure was also developed to find the possible multiple boundary layers and to derive an appropriate reduced model.</p> <p>Conclusion</p> <p>By successive calculation of the newly derived time-scale criteria, it was possible to detect multiple boundary layers of full ordinary differential equation (ODE) models. Besides, the iterative procedure could derive the appropriate reduced differential algebraic equation (DAE) model with consistent initial values, which was tested with simple examples and a practical example.</p

Effect of Regular Plyometric Training on Growth-related Factors in Obesity Female Teenager

OBJECTIVES This study aimed to investigate the effect of regular plyometric training on growth-related factors in obese female teenager. METHODS The subjects of the study consisted of elementary school students group (EG, n=5) and middle school students group(MG, n=6), and overweight or obese experimenters were selected based on the ‘2017 Child and Adolescent Growth Chart Age Body Mass’ index. Exercise was conducted for 12 weeks. All measurements were carried out before and after exercise. The data processing was verified using the SPSS 26.0 statistical program to verify the correlation between paired t-test and Pearson in the 12-week pretraining and post-training groups. RESULTS After 12 weeks of plyometric training, there were significant differences in height(p=.002), ASIS(p=.003), body fat percentage(p=.018), and muscle mass(p=.014) among body composition of EG. There was a significant difference in height(p=.015) in body composition of MG. In the evaluation of muscle function, in muscle strength(60°/sec), (R)-FLE PT/bw(p=.011), (L)-FLE PT/bw(p=.017) in EG and muscle power(180°/sec), (R)-FLE PT/bw(p=.024), (L)-EXT PT/bw(p=.001), (R)-FLE TW/bw(p=.004) and (L)-EXT TW/bw(p=.012) showed a statistically significant difference. In terms of correlation, significant relationships were found between EG body fat mass and IGF-1(p<.05), and between body fat mass and IGF-1/IGF-BP3(p<.05). CONCLUSIONS Regular plyometric training had a positive effect on growth-related factors in obese female teenager

A Versatile Approach to Ullmann C−N Couplings at Room Temperature: New Families of Nucleophiles and Electrophiles for Photoinduced, Copper-Catalyzed Processes

The use of light to facilitate copper-catalyzed cross-couplings of nitrogen nucleophiles can enable C−N bond formation to occur under unusually mild conditions. In this study, we substantially expand the scope of such processes, establishing that this approach is not limited to reactions of carbazoles with iodobenzene and alkyl halides. Specifically, we demonstrate for the first time that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles, benzimidazoles, and imidazoles) as well as other electrophiles (e.g., hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable partners. Photoinduced C−N bond formation can be achieved at room temperature using a common procedure with an inexpensive catalyst (CuI) that does not require a ligand coadditive and is tolerant of moisture and a variety of functional groups

A general, modular method for the catalytic asymmetric synthesis of alkylboronate esters

Alkylboron compounds are an important family of target molecules, serving as useful intermediates, as well as end points, in fields such as pharmaceutical science and organic chemistry. Facile transformation of carbon-boron bonds into a wide variety of carbon-X bonds (where X is, for example, carbon, nitrogen, oxygen, or a halogen), with stereochemical fidelity, renders the generation of enantioenriched alkylboronate esters a powerful tool in synthesis. Here we report the use of a chiral nickel catalyst to achieve stereoconvergent alkyl-alkyl couplings of readily available racemic α-haloboronates with organozinc reagents under mild conditions. We demonstrate that this method provides straightforward access to a diverse array of enantioenriched alkylboronate esters, in which boron is bound to a stereogenic carbon, and we highlight the utility of these compounds in synthesis

Temperature-evolution of spectral function and optical conductivity in heavy fermion compound Ce2_{2}IrIn8_{8} under crystalline electric field

We investigate the role of the crystalline electric field (CEF) in the temperature ($T$)-evolution of the Kondo resonance states and its effect on optical conductivity. We perform the combined first principles calculation of the density functional theory and dynamical mean field theory on Ce$_{2}$IrIn$_{8}$. The calculated spectral function reproduces the experimental observed CEF states at low $T$, while it shows a drastic change of the Fermi surface upon increasing $T$. The effect of the CEF states on the Fermi surface as a function of $T$ is elucidated through the first principles calculations as well as the analysis on the Anderson impurity model. Consequently, we suggest the importance of the CEF-driven orbital anisotropy in the low-energy states of optical experiments.Comment: 6 pages, 4 figure

Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis

An asymmetric decarboxylative C_(sp)^3–C_(sp)^2 cross-coupling has been achieved via the synergistic merger of photoredox and nickel catalysis. This mild, operationally simple protocol transforms a wide variety of naturally abundant α-amino acids and readily available aryl halides into valuable chiral benzylic amines in high enantiomeric excess, thereby producing motifs found in pharmacologically active agents