Добірка наукової літератури з теми "Organic synthesis, Catalysis, and methodology development"

The interplay between metals and N-heterocyclic carbenes (NHCs) has provided a window of opportunities for the development of novel catalytic strategies within the past few years. The recent successful combination of Brønsted acids with NHCs has added a new dimension to the field of cooperative catalysis, enabling the stereoselective synthesis of functionalized pyrrolidin-2-ones as valuable scaffolds in heterocyclic chemistry. This Commentary will briefly highlight the concept of N-heterocyclic carbene/Brønsted acid cooperative catalysis as a new and powerful methodology in organic chemistry.

N-heterocyclic carbene organocatalysis under oxidizing conditions provides a vast range of various synthetic procedures via diverse mechanisms. The available catalysts, bases, oxidants, and oxidizing methods afford numerous opportunities for developing this branch of organocatalysis. Furthermore, implementation of tandem reactions and cooperative catalysis in the described methodology significantly expands the possibilities of modern organic chemistry. This approach allows the synthesis of different structurally complex and often enantiomerically enriched substances, which can be interesting in terms of biological activity and natural product synthesis. Many esters, amides, thioesters, lactams, lactones, and other cyclic compounds obtained in oxidative or oxygenative reactions promoted by N-heterocyclic carbenes can be interesting precursors in advanced organic synthesis. Sophistication and broad applicability prove that the described synthetic approaches are exceptionally worthy of further development.

Tris(acetylacetonato) iron(III) [Fe(acac)3] is an indispensable reagent in synthetic chemistry. Its applications range from hydrogen atom transfer to cross-coupling reactions and to use as a Lewis acid. Consequently, the exceptional utility of Fe(acac)3 has been demonstrated in several total syntheses. This short review summarizes the applications of Fe(acac)3 in methodology and catalysis and highlights its use for the synthesis of medicinally relevant structures and in natural product syntheses.1 Introduction2 Hydrogen Atom Transfer (HAT)3 Oxidations and Radical Transformations4 Synthesis and Use of Alkynes and Allenes5 Cross-Couplings and Cycloisomerizations6 Borylations7 Miscellaneous Reactions8 Conclusions

This article addresses new developments in silver-catalyzed cyclization processes, resulting in the formation of carbocyclic or heterocyclic rings. Some essential techniques in organic chemistry include silver-catalyzed reactions. In addition, silver catalysts have been emerged as a novel catalysis in the last two decades. In these sequences, preparations of oxygen and nitrogen-containing heterocyclic compounds emerge as the most important development of new methodology. Silver catalysts exhibit significant reactivity in mild conditions in contrast to other transition metals such as copper, lead, zinc, ruthenium, gallium, indium, and niobium. These developments have lots of scientific attention due to their potential to synthesise of heterocyclic compounds in medicinal and agrochemical use. This current literature review summarises several silver-catalyzed oxo and aza-cyclization processes using readily available starting materials.

Nature provides us with a wonderful pool of enantiopure starting materials for synthesis: amino acids, sugars, and many (but not all!) terpenes can be isolated even in large quantities in an uncompromised 100 % ee. Vicinal amino alcohols constitute a versatile group of organic structures; they are, in principle, available in enantiopure form from the chiral pool compounds or through chiral catalysis; they are potent intermediates for the synthesis of natural products and medicinally/biologically active compounds, and they provide a highly desirable scaffold for the construction of ligands for metals as well as organocatalysts. These new techniques will open up valuable new possibilities for the invention of new technologies for chemical synthesis, the desired course of chemical discoveries for the future. A robust entry to enantiopure vicinal amino alcohols from inexpensive naturally occurring amino acids has therefore become a key challenge for our endeavors in the development of methodology.

Ying-Yeung Yeung received his B.Sc. (2001) at The Chinese University of Hong Kong. He continued his graduate research at the same university under the supervision of Prof. Tony K. M. Shing. After four years (2001–2005) of research dedicated toward natural product synthesis, he moved to the USA to conduct postdoctoral research with Prof. E. J. Corey at Harvard University (2005–2008). In 2008, he joined the National University of Singapore, Department of Chemistry. In 2015, he moved to The Chinese University of Hong Kong as an associate professor. He has been the department chairman (since 2016) and a full professor (since 2019). His research interests include asymmetric catalysis, green oxidation, and methodology development.

We present herein the development of a new synthetic strategy for the conjugation of 4,4′-bipyridinium derivatives into peptide scaffolds. The methodology, based on the development of a solid-phase version of the Zincke reaction between activated pyridinium salts and amines, is able to produce the desired conjugates in a straightforward fashion, with the bipyridinium units attached at the N-terminus of peptides or at Lys side chains of N-terminal acetylated peptides.

A long polyelectrolyte chain collapses into a nano-sized particle upon the addition of counterions under appropriate solution conditions. This phenomenon forms the basis for a simple universal method for aqueous synthesis of ultra-small (<10 nm) metal, metal oxide, and other types of nanoparticles in the following manner: the counterion-collapsed polyelectrolyte chains are made stable by crosslinking, effectively trapping the counterions, which are subsequently chemically modified, to form metal nanoparticles via reduction or metal oxides nanoparticles via oxidation, within the collapsed polymer nanoparticle. This highly versatile platform methodology can be applied to almost any polyelectrolyte–counterion pair, making possible the rapid development of syntheses of different nanoparticles within the same chemical environment. Using poly(acrylic acid) as a model system, a methodology for the optimization of conditions for the polyelectrolyte collapse by various mono- and multi-valent metal cations is developed. The optimal counterion concentration did not correlate with ionic strength and metal ion valency and was highly variable from system to system. By monitoring the polyelectrolyte conformation using viscosity and turbidity measurements, the appropriate metal ion concentration for each nanoparticle system was determined.

Abstract Despite numerous advantages, applications of conventional microporous metal–organic frameworks (MOFs) are hampered by their limited pore sizes, such as in heterogeneous catalysis and guest delivery, which usually involve large molecules. Construction of hierarchically porous MOFs (HP-MOFs) is vital to achieve the controllable augmentation of MOF pore size to mesopores or even macropores, which can enhance the diffusion kinetics of guests and improve the storage capacity. This review article focuses on recent advances in the methodology of HP-MOF synthesis, covering preparation of HP-MOFs with intrinsic hierarchical pores, and modulated, templated and template-free synthetic strategies for HP-MOFs. The key factors which affect the formation of HP-MOF architectures are summarized and discussed, followed by a brief review of their applications in heterogeneous catalysis and guest encapsulation. Overall, this review presents a roadmap that will guide the future design and development of HP-MOF materials with molecular precision and mesoscopic complexity.

This review describes the development of a new, synthetically useful method of asymmetric synthesis in organic photochemistry. Similar in many ways to the Pasteur procedure for resolving racemic carboxylic acids and organic amines, the method relies on the use of crystalline organic salts in which the enantioselectivity of a photochemical reaction of an achiral organic ion (for example, a carboxylate anion) is governed in the solid state by the presence of an optically pure counterion (for example, an optically active ammonium ion). Such optically pure counterions are termed ionic chiral auxiliaries. Salts containing ionic chiral auxiliaries are required to crystallize in chiral space groups, which provide the asymmetric environment necessary for chiral induction. Using this methodology, we have obtained near-quantitative optical yields in a wide variety of photochemical reactions.Key words: photochemistry, solid state, chiral auxiliaries, asymmetric synthesis, crystal structure–reactivity relationships.

A highly enantioselective acylation of silyl ketene acetals with acyl fluorides was developed to generate useful α,α-disubstituted butyrolactone products in high yield and excellent enantioselectivities. This transformation is promoted by an arylpyrrolidino thiourea catalyst and 4-pyrrolidinopyridine and represents the first example of enantioselective thiourea anion-binding catalysis with fluoride. Mechanistic investigations revealed both catalysts to be necessary for reaction to occur, suggesting the thiourea aids in the generation of the key N-acylpyridinium/fluoride ion pair. The outstanding hydrogen-bond-accepting ability of fluoride is likely important in this regard. In addition, a strong dependence on both the N-acylpyridinium counteranion and the substituents on the silicon group of the silyl ketene acetal were observed, highlighting the importance of the silicon-fluoride interaction. A cyclic oligomeric (salen)Co–OTf complex was used to catalyze a highly enantioselective addition of phenyl carbamate to meso-epoxides to afford protected trans-1,2-amino alcohols. The use of an oligomeric (salen)Co–OTf complex as the catalyst and aryl carbamates as nucleophiles was crucial to the development of this reaction protocol. This method is amenable to large-scale synthesis due to the low catalyst loadings and high concentration used, its operational simplicity, and the use of inexpensive, commercially-available starting materials. To demonstrate the synthetic utility of this protocol, optically pure trans-2-aminocyclohexanol hydrochloride and trans-2-aminocyclopentanol hydrochloride were prepared on a multigram scale using only 0.5 and 1 mol% catalyst loading, respectively.
Chemistry and Chemical Biology

Dans cette thèse les mécanismes de trois réactions catalysées par des complexes de palladium et de cuivre ont été étudiés en utilisant des méthodes expérimentales et théoriques. La première réaction est la synthèse d’amides à partir d’halogénoarènes, d’isonitriles et d’eau, qui est un exemple de couplage catalysé par le palladium impliquant l’insertion d’un isonitrile. Cette dernière molécule sert à la fois de ligand et de substrat, et son influence sur chaque étape du cycle catalytique a été mise en évidence. La deuxième réaction est l’ouverture des benzofuranes conduisant à des dérivés indoliques catalysée par des sels de palladium. Les conditions opératoires ont été optimisées et les étapes clés du mécanisme ont été élucidées.La dernière réaction étudiée, qui est le sujet principal de cette thèse, est l’addition d’amines sur des allènes catalysée par des sels de cuivre (hydroamination). La caractérisation des espèces catalytiques de cuivre(I) et l’étude théorique du mécanisme ont permis d’étendre cette réaction à différents substrats (allénamides, N-allénylazoles, N-allénylsulfamides) dans des conditions particulièrement douces et efficaces
In this thesis, the mechanism of three organic reactions catalyzed by palladium and copper complexes has been elucidated by the use of both experimental and theoretical methods. The first reaction is the synthesis of amides from haloarenes, isocyanides and water as an example of the broad family of palladium-catalyzed imidoylative couplings. Multiple roles of the isocyanide as both a ligand and a substrate in the different steps of the catalytic cycle have been disclosed. The second transformation is the palladium-catalyzed ring opening of benzofurans leading to indoles. Optimal conditions for this transformation have been found and the key aspects of its mechanism clarified. The last reaction, which is the main topic of this thesis, is the addition of amines to allenes catalyzed by copper salts (hydroamination). A characterization of the catalytically active copper(I) species and insight from theoretical calculations suggested how to extend this reaction to other substrates (allenamides, N-allenylazoles, N-allenylsulfonamides) under mild and efficient conditions

Thesis advisor: James P. Morken
This dissertation describes the development of various palladium-catalyzed syntheses of organoboron compounds with the 1,2-metallate shift of organoboron “ate” complexes as a common mechanistic feature. Chapter one discusses the history of the 1,2-metallate shift with a focus on reactions promoted by transition metals, followed by my work on the palladium-catalyzed, enantioselective, halide-tolerant conjunctive cross-coupling reaction to enable the use of Grignard reagents and arylbromides. Chapter two discusses the attempt to engage allylic electrophiles in the conjunctive cross-coupling reaction and the discovery and optimization of the vinylidenation reaction to access 1,1-disubstituted boryl alkenes. Unlike other palladium-catalyzed reactions that proceed by a 1,2-metallate shift, the vinylidenation proceeds by a β-hydride elimination rather than a reductive elimination as the final step in the catalytic cycle. Chapter three discusses the development of the enantioselective conjunctive cross-coupling of propargylic electrophiles to access enantioenriched β-boryl allenes. Methanol additive was found to improve both the yield and enantioselectivity of the reaction. 1H NMR studies show that methanol exchanges with the pinacol ligand on the boron “ate” complex
Thesis (PhD) — Boston College, 2020
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

The aim of this project was to utilize chiral cation-directed catalysis in the asymmetric synthesis of novel hererocycles. This goal was initially realized by the synthesis of azaindolines in high yields and enantioselectivities (Chapter 2). Extension of this methodology to substrates bearing two stereogenic centres was successful, although control over both diastereoselectivity and enantioselectivity in this process was modest. Finally the synthesis of heterocycles utilizing cation-directed rearrangement processes was examined, with proof of concept obtained for a novel asymmetric cyclization to form xanthenes.

A set of mild conditions for the pentafluorophenylation of carbonyl compounds employing copper-bisphosphine catalysis have been developed. The optimised conditions allow access to a wide range of pentafluorophenyl benzyl alcohols in high yields. The reaction of aliphatic aldehydes and particularly electrophilic ketones to give products in moderate yields is also disclosed. An investigation into the reactivity of β-fluoroalkyl-α ,β -unsaturated carbonyl compounds was conducted. Asymmetric copper hydride reduction of β -fluoroalkyl-α , β-unsaturated ketones was found to preferentially give the allylic alcohol product resulting from 1,2 attack in up to 62% ee. Reaction of β-fluoroalkyl-α , β-unsaturated esters under similar conditions gave the product of conjugate reduction in higher enantiomeric excess; up to 99% was observed. Rhodium-catalysed arylation of β -fluoroalkyl-α , β-unsaturated ketones was also found to give the product of direct carbonyl attack. Conditions for the racemic reaction are described along with those for the enantioselective reaction of methyl ketones in up to 74% ee. Ruthenium catalysed arylation of β-fluoroalkyl-α ,β -unsaturated aldehydes employing Me-Bipam as ligand gave the desired secondary allylic alcohols in good yields and good to excellent enantiomeric excesses (14 examples, 76-87% ee).

The synthesis of heterocycles using radical intermediates has become an important area of research in recent years. The aim of our research was to develop radical methodologies to construct heterocycles on solid-support. Tri-cyclic benzimidazole derivatives are desirable synthetic targets with a range of biological activity and are part of certain anti-tumour agents. Solid-supported radical reactions with substituted benzimidazoles were performed under different experimental conditions, including different solvents, three different resins (Wang, Merrifield and Rink) and different radical reagents. 4-Mercaptobenzoic acid moiety served as a traceless linker in radical ipso-substitution reactions of benzimidazole precursors attached to solid-support to construct tri-cyclic and tetracyclic benzimidazole adducts. The solution-phase radical ipso-substitution protocol was quite successfully translated onto solid-support.

In the following thesis, new methodologies towards the synthesis of a range of sulfonyl (-SO₂-) containing functional groups are documented. These methods utilise easy-to-handle sulfur dioxide surrogates, such as DABSO (vide infra), and exploit palladium catalysis as a new mechanistic protocol for the incorporation of the -SO2- unit. Chapter 1 is a literature review surveying sulfur dioxide in organic synthesis, the established uses of SO₂ surrogates and the importance of the sulfonyl moiety in chemistry. Palladium-catalysed (carbonylative) cross-couplings are also broadly discussed as they provide inspiration for, and mechanistic similarities with, the proposed chemistry. Chapter 2 describes a de novo synthesis of the sulfonamide functional group; a three-component and convergent methodology coupling (hetero)aryl and alkenyl halides with sulfur dioxide (provided by easy-to-handle surrogates such as DABSO) and hydrazine nucleophiles, is documented. This is achieved through the action of a readily available palladium catalytic system and is the first example of a metal-catalysed sulfonylative cross-coupling of halide based electrophiles. Chapter 3 presents a new method of generating (hetero)aryl and alkenyl sulfones. The ability of organometallic reagents to add to sulfur dioxide (supplied via DABSO) is applied to deliver the corresponding metal sulfinate salt. This in situ derived sulfinate is coupled with an (hetero)aryl or alkenyl (pseudo)halide using palladium catalysis to form the desired sulfone. An electronically modified XantPhos-type ligand was designed for the reaction in order to suppress unwanted aryl-aryl exchange. Chapter 4 documents the generation of (hetero)aryl and alkenyl sulfinates from the corresponding halide and DABSO through a palladium-catalysed sulfination protocol, obviating the need for organometallic reagents. A mild set of conditions using IPA as both a solvent and reductant together with a low loading of palladium catalyst offers an attractive route to sulfonyl compounds thanks to the in situ derived sulfinates being converted into a broad variety of functional groups via established onwards reactivity. Chapter 5 discusses the conclusion of the research and the potential for future work. Chapter 6 presents the experimental data.

Chemistry
Ph.D.
This thesis describes the synthesis of functionalized spiroligomers and their applications in metal binding, metal-mediated catalysis, and organocatalysis. By synthesizing a family of functionalized bis-amino acids achieved from reductive alkylation, the Schafmeister group has developed access to highly functionalized and shape programmable structures named “spiroligomers.” The rigid backbones of spiroligomers are good at organizing the orientations of functional groups on their side chains. This property enables them as promising candidates for catalysts. Firstly we synthesized a few spiroligomer dimers presenting metal-binding groups such as terpys and bipys. With the right orientation of metal binding groups controlled by adjusting the stereocenter of the spiroligomer, macrocyclic “square” complexes with metals were obtained. The crystal structures of these intriguing complexes were solved. This work rendered the first structurally, spectroscopically and electronically characterized metal-spiroligomer complexes as well as the first crystal structure of spiroligomer. Secondly, the question of whether metal-binding spiroligomers are able to catalyze certain reactions became our major concern. We developed a binuclear copper catalyst that could accelerate a phosphate ester rearrangement, and that demonstrated that when the two copper binding terpyridine groups were best able to approach each other, they accelerated the rearrangement more than 1,000 times faster than the background reaction. Other molecules that did not properly organize the two copper atoms demonstrate considerably slower reaction rates. At last, catalysts based on spiroligomers without metals are also of interests. By displaying two hydrophobic groups in various directions on a monomeric spiroligomer (also can be regarded as a proline derivative), we observed variable activities and enantioselectivities in the catalysis of asymmetric Michael addition (up to 94% ee at -40 °C for one organocatalyst).
Temple University--Theses

Total synthesis of the pyrrolizidine alkaloid NP25302: (+)-NP25302 is an unusual vinylogous urea containing pyrrolizidine alkaloid shown to exhibit cell adhesion inhibition. It was envisaged that this natural product could be accessed by a novel 5-endo-dig cyclisation to construct the pyrrolizidine core, and a Curtius rearrangement to install the vinylogous urea motif. This methodology was first tested on a model system, furnishing nor-NP25302 from L-proline in 12 steps and 9% overall yield. The total synthesis of (±)-NP25302 was completed in 9 steps and 26% overall yield from ethyl 2-nitropropionate using similar methodology. Studies into the stereospecificity of the Au(I)-catalysed cyclisation of monoallylic diols: During the synthesis of (+)-isoaltholactone in the Robertson group, the key Au(I)-catalysed cyclisation was observed to occur with some stereospecificity. Further investigations were therefore conducted into the stereochemical outcome of this reaction using stereodefined allylic alcohols, and from the combined results a mnemonic was proposed to predict the stereochemistry of the products of this reaction. Studies into the total synthesis of ascospiroketals A and B: Investigations were conducted into the total synthesis of the recently isolated natural products ascospiroketals A and B. A second generation synthesis was used to construct advanced intermediates 1 and 2.

Polymer Chemistry: A Practical Approach in Chemistry has been designed for both chemists working in and new to the area of polymer synthesis. It contains detailed instructions for preparation of a wide-range of polymers by a wide variety of different techniques, and describes how this synthetic methodology can be applied to the development of new materials. It includes details of well-established techniques, e.g. chain-growth or step-growth processes together with more up-to-date examples using methods such as atom-transfer radical polymerization. Less well-known procedures are also included, e.g. electrochemical synthesis of conducting polymers and the preparation of liquid crystalline elastomers with highly ordered structures. Other topics covered include general polymerization methodology, controlled/"living" polymerization methods, the formation of cyclic oligomers during step-growth polymerization, the synthesis of conducting polymers based on heterocyclic compounds, dendrimers, the preparation of imprinted polymers and liquid crystalline polymers. The main bulk of the text is preceded by an introductory chapter detailing some of the techniques available to the scientist for the characterization of polymers, both in terms of their chemical composition and in terms of their properties as materials. The book is intended not only for the specialist in polymer chemistry, but also for the organic chemist with little experience who requires a practical introduction to the field.

Bones are multifunctional passive organs of movement that supports soft tissue and directly attached muscles. They also protect internal organs and are a reserve of calcium, phosphorus and magnesium. Each bone is covered with periosteum, and the adjacent bone surfaces are covered by articular cartilage. Histologically, the bone is an organ composed of many different tissues. The main component is bone tissue (cortical and spongy) composed of a set of bone cells and intercellular substance (mineral and organic), it also contains fat, hematopoietic (bone marrow) and cartilaginous tissue. Bones are a tissue that even in adult life retains the ability to change shape and structure depending on changes in their mechanical and hormonal environment, as well as self-renewal and repair capabilities. This process is called bone turnover. The basic processes of bone turnover are: • bone modeling (incessantly changes in bone shape during individual growth) following resorption and tissue formation at various locations (e.g. bone marrow formation) to increase mass and skeletal morphology. This process occurs in the bones of growing individuals and stops after reaching puberty • bone remodeling (processes involve in maintaining bone tissue by resorbing and replacing old bone tissue with new tissue in the same place, e.g. repairing micro fractures). It is a process involving the removal and internal remodeling of existing bone and is responsible for maintaining tissue mass and architecture of mature bones. Bone turnover is regulated by two types of transformation: • osteoclastogenesis, i.e. formation of cells responsible for bone resorption • osteoblastogenesis, i.e. formation of cells responsible for bone formation (bone matrix synthesis and mineralization) Bone maturity can be defined as the completion of basic structural development and mineralization leading to maximum mass and optimal mechanical strength. The highest rate of increase in pig bone mass is observed in the first twelve weeks after birth. This period of growth is considered crucial for optimizing the growth of the skeleton of pigs, because the degree of bone mineralization in later life stages (adulthood) depends largely on the amount of bone minerals accumulated in the early stages of their growth. The development of the technique allows to determine the condition of the skeletal system (or individual bones) in living animals by methods used in human medicine, or after their slaughter. For in vivo determination of bone properties, Abstract 10 double energy X-ray absorptiometry or computed tomography scanning techniques are used. Both methods allow the quantification of mineral content and bone mineral density. The most important property from a practical point of view is the bone’s bending strength, which is directly determined by the maximum bending force. The most important factors affecting bone strength are: • age (growth period), • gender and the associated hormonal balance, • genotype and modification of genes responsible for bone growth • chemical composition of the body (protein and fat content, and the proportion between these components), • physical activity and related bone load, • nutritional factors: – protein intake influencing synthesis of organic matrix of bone, – content of minerals in the feed (CA, P, Zn, Ca/P, Mg, Mn, Na, Cl, K, Cu ratio) influencing synthesis of the inorganic matrix of bone, – mineral/protein ratio in the diet (Ca/protein, P/protein, Zn/protein) – feed energy concentration, – energy source (content of saturated fatty acids - SFA, content of polyun saturated fatty acids - PUFA, in particular ALA, EPA, DPA, DHA), – feed additives, in particular: enzymes (e.g. phytase releasing of minerals bounded in phytin complexes), probiotics and prebiotics (e.g. inulin improving the function of the digestive tract by increasing absorption of nutrients), – vitamin content that regulate metabolism and biochemical changes occurring in bone tissue (e.g. vitamin D3, B6, C and K). This study was based on the results of research experiments from available literature, and studies on growing pigs carried out at the Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences. The tests were performed in total on 300 pigs of Duroc, Pietrain, Puławska breeds, line 990 and hybrids (Great White × Duroc, Great White × Landrace), PIC pigs, slaughtered at different body weight during the growth period from 15 to 130 kg. Bones for biomechanical tests were collected after slaughter from each pig. Their length, mass and volume were determined. Based on these measurements, the specific weight (density, g/cm3) was calculated. Then each bone was cut in the middle of the shaft and the outer and inner diameters were measured both horizontally and vertically. Based on these measurements, the following indicators were calculated: • cortical thickness, • cortical surface, • cortical index. Abstract 11 Bone strength was tested by a three-point bending test. The obtained data enabled the determination of: • bending force (the magnitude of the maximum force at which disintegration and disruption of bone structure occurs), • strength (the amount of maximum force needed to break/crack of bone), • stiffness (quotient of the force acting on the bone and the amount of displacement occurring under the influence of this force). Investigation of changes in physical and biomechanical features of bones during growth was performed on pigs of the synthetic 990 line growing from 15 to 130 kg body weight. The animals were slaughtered successively at a body weight of 15, 30, 40, 50, 70, 90, 110 and 130 kg. After slaughter, the following bones were separated from the right half-carcass: humerus, 3rd and 4th metatarsal bone, femur, tibia and fibula as well as 3rd and 4th metatarsal bone. The features of bones were determined using methods described in the methodology. Describing bone growth with the Gompertz equation, it was found that the earliest slowdown of bone growth curve was observed for metacarpal and metatarsal bones. This means that these bones matured the most quickly. The established data also indicate that the rib is the slowest maturing bone. The femur, humerus, tibia and fibula were between the values of these features for the metatarsal, metacarpal and rib bones. The rate of increase in bone mass and length differed significantly between the examined bones, but in all cases it was lower (coefficient b <1) than the growth rate of the whole body of the animal. The fastest growth rate was estimated for the rib mass (coefficient b = 0.93). Among the long bones, the humerus (coefficient b = 0.81) was characterized by the fastest rate of weight gain, however femur the smallest (coefficient b = 0.71). The lowest rate of bone mass increase was observed in the foot bones, with the metacarpal bones having a slightly higher value of coefficient b than the metatarsal bones (0.67 vs 0.62). The third bone had a lower growth rate than the fourth bone, regardless of whether they were metatarsal or metacarpal. The value of the bending force increased as the animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. The rate of change in the value of this indicator increased at a similar rate as the body weight changes of the animals in the case of the fibula and the fourth metacarpal bone (b value = 0.98), and more slowly in the case of the metatarsal bone, the third metacarpal bone, and the tibia bone (values of the b ratio 0.81–0.85), and the slowest femur, humerus and rib (value of b = 0.60–0.66). Bone stiffness increased as animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. Abstract 12 The rate of change in the value of this indicator changed at a faster rate than the increase in weight of pigs in the case of metacarpal and metatarsal bones (coefficient b = 1.01–1.22), slightly slower in the case of fibula (coefficient b = 0.92), definitely slower in the case of the tibia (b = 0.73), ribs (b = 0.66), femur (b = 0.59) and humerus (b = 0.50). Bone strength increased as animals grew. Regardless of the growth point tested, bone strength was as follows femur > tibia > humerus > 4 metacarpal> 3 metacarpal> 3 metatarsal > 4 metatarsal > rib> fibula. The rate of increase in strength of all examined bones was greater than the rate of weight gain of pigs (value of the coefficient b = 2.04–3.26). As the animals grew, the bone density increased. However, the growth rate of this indicator for the majority of bones was slower than the rate of weight gain (the value of the coefficient b ranged from 0.37 – humerus to 0.84 – fibula). The exception was the rib, whose density increased at a similar pace increasing the body weight of animals (value of the coefficient b = 0.97). The study on the influence of the breed and the feeding intensity on bone characteristics (physical and biomechanical) was performed on pigs of the breeds Duroc, Pietrain, and synthetic 990 during a growth period of 15 to 70 kg body weight. Animals were fed ad libitum or dosed system. After slaughter at a body weight of 70 kg, three bones were taken from the right half-carcass: femur, three metatarsal, and three metacarpal and subjected to the determinations described in the methodology. The weight of bones of animals fed aa libitum was significantly lower than in pigs fed restrictively All bones of Duroc breed were significantly heavier and longer than Pietrain and 990 pig bones. The average values of bending force for the examined bones took the following order: III metatarsal bone (63.5 kg) <III metacarpal bone (77.9 kg) <femur (271.5 kg). The feeding system and breed of pigs had no significant effect on the value of this indicator. The average values of the bones strength took the following order: III metatarsal bone (92.6 kg) <III metacarpal (107.2 kg) <femur (353.1 kg). Feeding intensity and breed of animals had no significant effect on the value of this feature of the bones tested. The average bone density took the following order: femur (1.23 g/cm3) <III metatarsal bone (1.26 g/cm3) <III metacarpal bone (1.34 g / cm3). The density of bones of animals fed aa libitum was higher (P<0.01) than in animals fed with a dosing system. The density of examined bones within the breeds took the following order: Pietrain race> line 990> Duroc race. The differences between the “extreme” breeds were: 7.2% (III metatarsal bone), 8.3% (III metacarpal bone), 8.4% (femur). Abstract 13 The average bone stiffness took the following order: III metatarsal bone (35.1 kg/mm) <III metacarpus (41.5 kg/mm) <femur (60.5 kg/mm). This indicator did not differ between the groups of pigs fed at different intensity, except for the metacarpal bone, which was more stiffer in pigs fed aa libitum (P<0.05). The femur of animals fed ad libitum showed a tendency (P<0.09) to be more stiffer and a force of 4.5 kg required for its displacement by 1 mm. Breed differences in stiffness were found for the femur (P <0.05) and III metacarpal bone (P <0.05). For femur, the highest value of this indicator was found in Pietrain pigs (64.5 kg/mm), lower in pigs of 990 line (61.6 kg/mm) and the lowest in Duroc pigs (55.3 kg/mm). In turn, the 3rd metacarpal bone of Duroc and Pietrain pigs had similar stiffness (39.0 and 40.0 kg/mm respectively) and was smaller than that of line 990 pigs (45.4 kg/mm). The thickness of the cortical bone layer took the following order: III metatarsal bone (2.25 mm) <III metacarpal bone (2.41 mm) <femur (5.12 mm). The feeding system did not affect this indicator. Breed differences (P <0.05) for this trait were found only for the femur bone: Duroc (5.42 mm)> line 990 (5.13 mm)> Pietrain (4.81 mm). The cross sectional area of the examined bones was arranged in the following order: III metatarsal bone (84 mm2) <III metacarpal bone (90 mm2) <femur (286 mm2). The feeding system had no effect on the value of this bone trait, with the exception of the femur, which in animals fed the dosing system was 4.7% higher (P<0.05) than in pigs fed ad libitum. Breed differences (P<0.01) in the coross sectional area were found only in femur and III metatarsal bone. The value of this indicator was the highest in Duroc pigs, lower in 990 animals and the lowest in Pietrain pigs. The cortical index of individual bones was in the following order: III metatarsal bone (31.86) <III metacarpal bone (33.86) <femur (44.75). However, its value did not significantly depend on the intensity of feeding or the breed of pigs.

Catalysis by soluble complexes of transition metals is a rapidly gaining mode of catalysis in organic synthesis. These metals form bonds with one or more carbons in an organic reactant resulting in complexes that are known as organometallic complexes. Catalysis by these complexes is often referred to as homogeneous catalysis. Among the important applications of homogeneous catalysis in organic synthesis are isomerization of olefins; hydrogenation of olefins (carried out using Wilkinson type catalysts); oligomerization; hydroformylation of olefins to aldehydes with CO and H2 (the oxo process); carbonylation of unsaturated hydrocarbons and alcohols with CO (and coreactants such as water); oxidation of olefins to aldehydes, ketones, and alkenyl esters (Wacker process); and metathesis of olefins (a novel kind of disproportionation). Enantioselective catalysis that rivals enzymes in selectivity is a major development in homogeneous catalysis. As a result, many earlier processes in the pharmaceutical and perfumery industries are being replaced by more elegant syntheses using soluble catalysts in which “handedness” is introduced in the critical step of the process, thus avoiding the costly separation of racemic mixtures. In view of its importance in organic synthesis, enantioselective (or asymmetric) catalysis was briefly introduced in Chapter 6 and is again considered as a powerful synthetic tool in Chapter 9. This chapter is concerned with the use in general of homogeneous catalysis in organic synthesis (including asymmetric synthesis). Among the several books and reviews written on the subject, the following may be mentioned: Halpern (1975, 1982), Bau et al. (1978), Parshall (1980), Masters (1981), Collman and Hegedus (1980), Eby and Singleton (1983), Chaudhari (1984), Davidson (1984), Kegley and Pinhas (1986), Collman et al. (1987), Parshall and Nugent (1988), Noyori and Kitamura (1989), Parshall and Ittel (1992), Gates (1992), Chan (1993), Akutagawa (1995). Gas (or liquid)-phase reactions on solid catalysts are among the most common industrial reactions. However, homogeneous catalysis is rapidly catching up. Excluding applications in petroleum refining, the dollar value of organic chemicals produced worldwide by homogeneous catalysis (more than $35 billion) is quite impressive compared to that by heterogeneous catalysis (more than $45 billion). Attempts are now under way to find an integrated approach to homogeneous and heterogeneous catalyses (Moulijn et al., 1993).

AbstractThe combination of transition-metal catalysis and visible-light photocatalysis offers opportunities for the development of unique new forms of reactivity. Presented in this chapter is an overview of the various strategies that can be used to design these dual catalytic transformations. Emphasis is placed on understanding the specific role that a photocatalyst can play in augmenting the reactivity of a substrate or cocatalyst to achieve otherwise challenging transformations.

Erick M. Carreira at ETH Zürich reported (Science 2013, 340, 1065) the enantiose­lective α-allylation of aldehyde 1 with alcohol 2 to produce 3 using a dual catalytic system involving a chiral iridium complex and amine 5. This stereodivergent method allows access to all of the possible stereoisomers of 3. In a conceptually related proc­ess, John F. Hartwig at the University of California, Berkeley reported (J. Am. Chem. Soc. 2013, 135, 2068) the highly stereoselective allylic alkylation of azlactone 6 with allylic carbonate 7 catalyzed by a combination of Ir(cod)Cl₂, ligand 9, and racemic silver phosphate 10. An enantioselective three-component Mannich-type reaction of tert-butyl diazo­acetate, aniline, and imine 11 to produce α,β-bis(arylamino) acid derivative 13 under dual catalysis with Rh₂(OAc)₄ and acid 12 was developed (Synthesis 2013, 45, 452) by Wenhao Hu at the Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development. Keiji Maruoka at Kyoto University reported (Chem. Commun. 2013, 49, 1118) a one-pot cross double-Mannich reaction of acetylalde­hyde 14, and imines 16 and 17 using axially chiral amino sulfonamide 15 to obtain densely functionalized 1,3-diamine 18 as a single stereoisomer. Jeffrey S. Johnson at the University of North Carolina at Chapel Hill reported (Org. Lett. 2013, 15, 2446) the asymmetric synthesis of enantioenriched anti-α-hydroxy-β-amino acid derivative 21 from 19 by treatment with oxone followed by catalytic hydrogenation using Ru(II) complex 20. Naoya Kumagai and Masakatsu Shibasaki at the Institute of Microbial Chemistry found (Org. Lett. 2013, 15, 2632) that a sil­ver complex of bisphosphine 24 effected a syn-selective and highly enantioselective Mannich-type reaction of aldimine 22 and α-sulfanyl lactone 23 to furnish the stereo­diad 25 with very high ee. The enantioselective homocrotylation of octanal 26 with cyclopropylcarbinylbo­ronate 27 to produce alcohol 28 with high ee was disclosed (J. Am. Chem. Soc. 2013, 135, 82) by Isaac J. Krauss at Brandeis University with computational studies pro­vided by Kendall N. Houk at UCLA. Benjamin List at the Max-Planck-Institut für Kohlenforschung reported (J. Am. Chem. Soc. 2013, 135, 6677) the enantioselective epoxidation of cyclohexenone 29 utilizing cinchona alkaloid- derived catalyst 30.

Nabyl Merbouh and Robert Britton of Simon Fraser University developed (Eur. J. Org. Chem. 2013, 3219) a general route to a 2,5-disubstituted furan 3 by taking advantage of the ready α-chlorination of an aldehyde 1, followed by coupling with a ketone eno­late 2. Jérôme Waser of the Ecole Polytechnique Fédérale de Lausanne used (Angew. Chem. Int. Ed. 2013, 52, 6743) 5 to oxidize the allene 4 to the furan 6. Qian Zhang and Xihe Bi of Northeast Normal University used (Angew. Chem. Int. Ed. 2013, 52, 6953) Ag catalysis to prepare the pyrrole 9 by coupling the alkyne 7 with the isonitrile 8. Aiwen Lei of Wuhan University reported (Angew. Chem. Int. Ed. 2013, 52, 6958) similar results. Professor Lei also developed (Chem. Commun. 2013, 49, 5853) the Pd-catalyzed oxidation of the allyl imine 10 to the pyrrole 11. Kamal K. Kapoor of the University of Jammu reduced (Tetrahedron Lett. 2013, 54, 5699) the Michael adduct 12 to the pyrrole 13 with triethyl phosphite. Edgar Haak of the Otto-von-Guericke-Universität, Magdeburg condensed (Eur. J. Org. Chem. 2013, 7354) the alkynyl carbinol 14 with aniline to give the N-phenyl pyrrole 15. Jean Rodriguez and Thierry Constantieux of Aix-Marseille Université prepared (Eur. J. Org. Chem. 2013, 4131) the pyridine 18 by combining the ketone 16 and the unsaturated aldehyde 17 with NH4OAc. Teck-Peng Loh of the University of Sciences and Technology of China and Nanyang Technological University found (Angew. Chem. Int. Ed. 2013, 52, 8584) that TMEDA was an effective organocatalyst for the assembly of the pyridine 21 from 19 and 20. Andrew D. Smith of the University of St Andrews showed (Angew. Chem. Int. Ed. 2013, 52, 11642) that the pyridyl tosylate 24, avail­able by the combination of 22 and 23, readily coupled with both carbon and amine nucleophiles. In a related development, D. Tyler McQuade of Florida State University prepared (Org. Lett. 2013, 15, 5298) the 2-bromopyridine 26 from the alkylidene malononitrile 25. Two versatile approaches to substituted indoles were recently described. David F. Wiemer of the University of Iowa cyclized (J. Org. Chem. 2013, 78, 9291) the Stobbe product 27 to the 3-bromo indole 28.

Like zeolites that combine shape selectivity with catalysis, membranes combine separation with catalysis to enhance reaction rates. The dual functionality of zeolites derives from the nature of the catalytic material, whereas that of membranes derives from the nature of the reactor material. The catalyst in the membrane reactor can be a part of the membrane itself or be external to it (i.e., placed inside the membrane tube). The chief property of a membrane is its ability for selective permeation or permselectivity with respect to certain compounds. Organic membrane reactions are best carried out in reactors made of inorganic membranes, such as from palladium, alumina, or ceramics. Good descriptions of these reactions and the membranes used are available in many reviews, for example, Gryaznov (1986, 1992), Stoukides (1988), Armor (1989), Govind and Ilias (1989), Bhave (1991), Zaspalis and Burggraaf (1991), Hsieh (1989, 1991), Shu et al. (1991), Shieh (1991), Gellings and Bouwmeister (1992), Tsotsis et al. (1993b), Harold et al. (1994), Saracco and Specchia (1994), Sanchez and Tsotsis (1996). A recent trend has been to develop polymeric-inorganic composite type membranes formed by the deposition of a thin dense polymeric film on an inorganic support (Kita et al., 1987; Rezac and Koros, 1994, 1995; Zhu et al., 1996). Another class of membranes under development for organic synthesis is the liquid membrane (Marr and Kopp, 1982; Eyal and Bressler, 1993). The permselective barrier in this type of membrane is a liquid phase, often containing a dissolved “carrier” or “transporter” that selectively reacts with a specific permeate to enhance its transport rate through the membrane. Our main concern in this chapter will be with inorganic membrane reactors. We commence our treatment with an introduction to the exploitable features of membrane reactors (with no attempt to describe membrane synthesis). Then we describe the main variations in design and operating mode of these reactors, develop performance equations for the more important designs, and compare the performances of some important designs with those of the traditional mixed- and plug-flow reactors. Finally, we present a summary of the applications of membrane reactors in enhancing the rates of organic reactions.

The search for cost-effective and environmental benign practices for the production of bioactive compounds has gained considerable attention since last decade, due to increasing demand of eco-friendly processes. Many industries have started adopting routes for the development of green chemistry by employing enzymatic approaches to overcome the limitations of physico-chemical methods and environmental concerns. Laccase is one such enzyme which has gained considerable attention in recent years as a biocatalyst in organic synthesis. Laccases possess versatile biochemical properties and the reactions catalyzed by laccase require only molecular oxygen with concomitant release of water as a byproduct. They have been widely used for reactions such as dimerization, polymerization, coupling, and grafting reactions and for antibiotic modifications. This chapter summarizes the advances that have been made in developing technologies based on laccase mediated reactions in the field of medicine, agriculture, food, and pharmaceuticals.

Nowadays Carbon Nanomaterials (CNMs) are important in the applied nanoscience development, due to their extraordinary chemical and physical properties. The present research proposes a Taguchi methodology to obtain CNMs with high carbon concentration using hexane as carbon source, and stainless steel core as catalysis by Chemical Vapor Deposition (CVD). The Taguchi experimental design identified the optimal variable and level. Flow rate, temperature and time synthesis were studied. Scanning Electronic Microscopy (SEM) depicted different carbon morphologies. Energy Dispersive Spectroscopy (EDS) demonstrated a carbon atomic percentage concentration above 97. Temperature was the most significant variable according to Taguchi analysis.

It is nowadays admitted that microwaves are frequently used in organic chemistry labs [1] (even if not as much as it was predicted 20 years ago, one must say [2]). On the other side it is also certain that this technology has not yet found its place in chemical industry: application at a production scale are very scarce [3][4] and this despite the potential advantages of the technology (selective heating, high heating rate, low thermal inertia…). The point is that mastering all the aspects of microwaves assisted synthesis at industrial scale demands a lot of different skills to work together: chemistry, process engineering, microwave engineering, materials science. This is so challenging that tools and methodologies for quantification of industrial microwave interest and scaling-up of lab results are missing. In this work we present our contributions to the deployment of microwaves for synthesis in the chemical industry which are mainly The development of small pilot reactors (1 L) in stainless steel, capable to withstand temperature and pressureThe application of a chemical engineering methodology to microwave assisted synthesisAn example of intensification (see table) of an industrially interesting reaction using microwave to access NPW (high temperature and pressure)A tentative of rationalization of process criteria to identify a priori the interest of microwave heating for a specific application [1]. Diaz-Ortiz et al., Chem. Rec. 2019, 19, 85–97 [2]. Kappe, Chem. Rec. 2019, 19, 15–39 [3]. Aldivia, brevet WO2004/066683A1 [4]. https://cen.acs.org/articles/94/i36/Microwaving-ton.html

Работа представляет собой продолжение комплексных исследований в целом сформировавшейся ландшафтной школы профессора В.Т. Старожилова (doi:10.24411/1728-323Х-2020-13079, doi:10.18411/lj-05-2020-26). Рассматриваются районирование и структурная организация ландшафтных областей Тихоокеанского ландшафтного пояса России (doi: 10.18411/lj-01-2021-32), включающего Сихотэ-Алинскую, Нижнеамурскую, Камчатско-Курильскую, Сахалинскую и другие ландшафтные области и сопряженные с ними окраинные моря. Констатируется, что на основе применения ландшафтной методологии, на основе сопряженного анализа и синтеза межкомпонентных и межландшафтных связей с учетом окраинно-континентальной дихотомии и данных по орогеническому, орографическому, климатическому и фиторастительному факторам формирования географически единых территорий в рамках горного ландшафтоведения, проведено районирование ландшафтных областей и выделены горные и равнинные провинции. В Сихотэ-Алинской области - Самаргинская, Северо-Сихотэ-Алинская, Восточно-Сихотэ-Алинская, Центрально-Сихотэ-Алинская, Западно-Сихотэ-Алинская, Западно-Приморская равнина, Восточно-Маньчжурская, Южно-Приморская; в Сахалинской - Восточно-Сахалинская, Западно-Сахалинская, Центрально-Сахалинская и Северо-Сахалинская; в Камчатско – Курильской - Западно-Камчатская, Срединно-Камчатская, Центрально-Камчатская, Восточно-Камчатская провинции. Они является одной из базовых моделей «фундаментом» для построения гармонизированных с природой и связанных с океаном экологических, сельскохозяйственных и других отраслевых моделей освоения, в целом пространственного развития областей и их провинций. Отмечается, что при исследовании применялись компьютерные технологии векторно-слоевого ландшафтного метода, которые в свою очередь создают платформу для разработки планов и проектов освоения. Они также является платформой для обучения студентов. Приводятся данные о картографической обеспеченности современными векторно-слоевыми цифровыми материалами. Work is a continuation of comprehensive studies in general formed by the Landscape School of Professor V.T. Old-timer (DOI: 10.24411 / 1728-323x-2020-13079, DOI: 10.18411 / LJ-05-2020-26). The zoning and structural organization of the landscape areas of the Pacific Landscaping Belt of Russia are considered (DOI: 10.18411 / LJ-01-2021-32), which includes Sikhote-Alin, Nizhnemur, Kamchatka-Kuril, Sakhalin and other landscape areas and conjugate seas. It is stated that, on the basis of the use of landscape methodology, based on the conjugate analysis and synthesis of intercompontent and intercompound and intercompoundal dichotomy and orogenic, orographic, climatic data and the formation of geographically unified territories in the framework of mountain landscape, the landscape regions and Mountain and flat provinces are highlighted. In the Sikhote-Alina region - Samaginskaya, North-Sikhote-Alinsky, East-Sikhote-Alinsky, Central-Sikhote-Alinskaya, West Sikhote-Alinskaya, West Primorskaya Plain, East Manchu, South Primorskaya; in Sakhalin - East Sakhalin, West Sakhalin, Central Sakhalin and North-Sakhalin; In Kamchatsko - Kuril - West Kamchatka, Mid-Kamchatka, Central Kamchatka, East Kamchatka provinces. They are one of the basic models "foundation" to build harmonized with nature and the ocean-related environmental, agricultural and other sectoral models of development, in general, the spatial development of areas and their provinces. It is noted that the study used computer technology of the vector-layered landscape method, which in turn create a platform for developing plans and development projects. They are also a platform for students learning. The data on the cartographic provision of modern vector-layer digital materials are given.