Nitroxides: applications in synthesis and in polymer chemistry

This Review describes the application of nitroxides to synthesis and polymer chemistry. The synthesis and physical properties of nitroxides are discussed first. The largest section focuses on their application as stoichiometric and catalytic oxidants in organic synthesis. The oxidation of alcohols and carbanions, as well as oxidative C-C bond-forming reactions are presented along with other typical oxidative transformations. A section is also dedicated to the extensive use of nitroxides as trapping reagents for C-centered radicals in radical chemistry. Alkoxyamines derived from nitroxides are shown to be highly useful precursors of C-centered radicals in synthesis and also in polymer chemistry. The last section discusses the basics of nitroxide-mediated radical polymerization (NMP) and also highlights new developments in the synthesis of complex polymer architectures.     

Enzymes as Catalysts in Synthetic Organic Chemistry [New Synthetic Methods (53)]

Enzymes have great potential as catalysts for use in synthetic organic chemistry. Applications of enzymes in synthesis have so far been limited to a relatively small number of largescale hydrolytic processes used in industry, and to a large number of small-scale syntheses of materials used in analytical procedures and in research. Changes in the technology for production of enzymes (in part attributable to improved methods from classical microbiology, and in part to the promise of genetic engineering) and for their stabilization and manipulation now make these catalysts practical for wider use in large-scale synthetic organic chemistry. This paper reviews the status of the rapidly developing field of enzyme-catalyzed organic synthesis, and outlines both present opportunities and probable future developments in this field.     

Carbene Complexes in Organic Synthesis [New Synthetic Methods (47)]

Transition metals are finding increasing use in organic synthesis on the borderline between “organic” and “inorganic” chemistry. Advantage is taken thereby of the fact that metal-induced CC bond formation often takes place with remarkable selectivity. The rapid development that has taken place in this area of chemistry is clearly demonstrated by the carbene complexes, examples of which are now known for almost all transition elements, and which have transformed from organometallic curiosities into synthetically useful reagents in less than two decades since the first studies of E. O. Fischer. They are not only suitable as carbene-transfer agents but also undergo interesting cycloadditions with other ligands in the co-ligand sphere. Their manipulation requires techniques no more complicated than those for Grignard reactions. Thus, carbene complexes can also be used in the synthesis of natural products such as vitamins or antibiotics.     

Continuous Flow Synthesis of a Zr Magnetic Framework Composite for Post-Combustion CO2 Capture

Metal-organic frameworks (MOFs) have an unprecedented ability to store gas molecules, however energy efficient regeneration remains challenging. Use of magnetic induction to aid this shows promise, but economical synthesis of the requisite composites is unresolved. Continuous flow chemistry has been reported as a rapid and reliable method of MOF synthesis, delivering step-change improvements in space time yields (STY). Here the scalable production of nanomaterials suitable for regeneration by magnetic induction is demonstrated. The zirconium MOF composite, MgFe₂O₄@UiO-66-NH₂ is prepared using continuous flow chemistry resulting in a material of comparable performance to its batch counterpart. Upscaling using flow chemistry gave STY >25 times that of batch synthesis. Magnetic induced regeneration using this mass produced MFC for carbon capture is then demonstrated.     

Preparative solid state chemistry. Recent developments

A survey of recent developments in preparative solid state chemistry shows that, with a knowledge of structural chemistry and reactivity patterns of solids, it is possible to synthesize a variety of new solids possessing novel structures. A distinction is made between synthesis ofnew solids and synthesis of solids bynew methods. Three new routes to solid state synthesis are recognized: the precursor method, and topochemical methods involving redox and ion-exchange reactions. The low-temperature topochemical methods enable synthesis of metastable phases that are inaccessible by the high temperature route. Several illustrative examples of solid state synthesis from the recent literature are presented.     

Cu(OTf)2/NBS Promoted Cyclization of 1-Cinnamyl Alcohol-o-Carboranes: An Efficient Approach for Synthesis of o-Carboranes Substituted Oxetanes

The Cu(OTf)₂/NBS promoted cyclization of 1-cinnamyl alcohol-o-carboranes for synthesis of o-carborane substituted oxetanes has been developed. A series of substituted oxetanes has been synthesized with moderate to good yields, which would be an important synthon for design novel reactions in oxetane chemistry as well as carborane chemistry.     

Flash chemistry: fast chemical synthesis by using microreactors

This concept article provides a brief outline of the concept of flash chemistry for carrying out extremely fast reactions in organic synthesis by using microreactors. Generation of highly reactive species is one of the key elements of flash chemistry. Another important element of flash chemistry is the control of extremely fast reactions to obtain the desired products selectively. Fast reactions are usually highly exothermic, and heat removal is an important factor in controlling such reactions. Heat transfer occurs very rapidly in microreactors by virtue of a large surface area per unit volume, making precise temperature control possible. Fast reactions often involve highly unstable intermediates, which decompose very quickly, making reaction control difficult. The residence time can be greatly reduced in microreactors, and this feature is quite effective in controlling such reactions. For extremely fast reactions, kinetics often cannot be used because of the lack of homogeneity of the reaction environment when they are conducted in conventional reactors such as flasks. Fast mixing using micromixers solves such problems. The concept of flash chemistry has been successfully applied to various organic reactions including a) highly exothermic reactions that are difficult to control in conventional reactors, b) reactions in which a reactive intermediate easily decomposes in conventional reactors, c) reactions in which undesired byproducts are produced in the subsequent reactions in conventional reactors, and d) reactions whose products easily decompose in conventional reactors. The concept of flash chemistry can be also applied to polymer synthesis. Cationic polymerization can be conducted with an excellent level of molecular-weight control and molecular-weight distribution control.     

Analysis of Low Molecular Weight Homologues of Fiber-Forming Polycondensates

Oligomers belong to the gray area between low molecular weight chemistry and macromolecular chemistry. Although they represent an undesirable “natural impurity” in fiber-forming polycondensates, they serve as useful model compounds for the corresponding polymers in fundamental research. Whereas for many years new classes of oligomers were being made preparatively accessible and the isolation of higher oligomers in pure form was being pursued, at the present time the emphasis is on analysis. By a combination of classical chemical and instrumental methods of analysis from polymer and organic chemistry, the identification of oligomers of unknown structure, the analytical control of their synthesis and the determination of their content in technical polymers has meanwhile become a routine task.     

Cyclotriphosphate: A Brief History,Recent Developments,and Perspectives in Synthesis

There has been a recent upsurge in the study and application of approaches utilizing cyclotriphosphate 1 (cyclo-TP, also known as trimetaphosphate, TMP) and/or proceeding through its analogues in synthetic chemistry to access modified oligo- and polyphosphates. This is especially useful in the area of chemical nucleotide synthesis, but by no means restricted to it. Enabled by new high yielding and easy-to-implement methodologies, these approaches promise to open up an area of research that has previously been underappreciated. Additionally, refinements of concepts of prebiotic phosphorylation chemistry have been disclosed that ultimately rely on cyclo-TP 1 as a precursor, placing it as a potentially central compound in the emergence of life. Given the importance of such concepts for our understanding of prebiotic chemistry in combination with the need to readily access modified polyphosphates for structural and biological studies, this paper will discuss selected recent developments in the field of cyclo-TP chemistry, briefly touch on ultraphosphate chemistry, and highlight areas in which further developments can be expected.     

Perspectives in total synthesis: a personal account

Endeavors in total synthesis provide unique opportunities to discover and invent new strategies and tools for constructing organic molecules and they shape the art, science, and technology of chemical synthesis. In this article, the author reflects back on his career highlighting a number of lucrative campaigns in this field and their impact on chemistry, biology and medicine.     

Ring-closing metathesis as a basis for the construction of aromatic compounds

The use of metathesis, especially in the context of ring-closing metathesis (RCM) to form five- and six-membered rings, is widespread in organic chemistry today. However, there are surprisingly few examples of the reaction being used to form aromatic compounds. The central place of aromatic compounds in both medicinal chemistry and natural products synthesis, coupled with the efficiency and functional group tolerance of RCM catalysts, means that there is now an interesting opportunity to use RCM for the synthesis of arenes. Although the formation of an aromatic compound was viewed in many early examples as an undesirable degradation product, several rationally designed methods towards the preparation of aromatic compounds by RCM have recently been developed.     

Recent Advances in Transition‐Metal‐Free Oxygenation of Alkene C=C Double Bonds for Carbonyl Generation

Carbonyl‐forming reactions are a class of fundamental transformations in organic chemistry. Guided by the current importance of environmentally benign metal‐free catalysis and synthesis, herein we review recent advances in carbonyl‐generation reactions based on alkene C=C double oxygenation as well as related cascade reactions in the synthesis of diverse organic products. The content of this focus review consists of two important but different reaction models: oxygenation based on full C=C double‐bond cleavage and oxygenation based on partial C=C double‐bond cleavage.     

Continuous Flow Organic Synthesis under High‐Temperature/Pressure Conditions

Microreactor technology and continuous flow processing in general are key features in making organic synthesis both more economical and environmentally friendly. When preformed under a high‐temperature/pressure process intensification regime many transformations originally not considered suitable for flow synthesis owing to long reaction times can be converted into high‐speed flow chemistry protocols that can operate at production‐scale quantities. This Focus Review summarizes the state of the art in high‐temperature/pressure microreactor technology and provides a survey of successful applications of this technique from the recent synthetic organic chemistry literature.     

Inverse‐Electron‐Demand Diels–Alder Reactions: Principles and Applications

Inverse‐electron‐demand Diels–Alder (iEDDA) reactions are an intriguing class of cycloaddition reactions that have attracted increasing attention for their application in bioorthogonal chemistry, the total synthesis of natural products, and materials science. In many cases, the application of the iEDDA reaction has been demonstrated as an innovative approach to achieve target structures. The theoretical aspects of this class of reactions are of particular interest for scientists as a means to understand the various factors, such as steric strain and electron density of the attached groups, that govern the reaction and thus to elucidate the reaction mechanism. This review aims to summarize both theoretical investigations and application‐driven research work on the iEDDA reaction. First, the historical aspects and the theoretical basis of the reaction, especially recent advances in time‐dependent density functional theory (TD‐DFT) calculations, as well as catalysis strategies will be highlighted and discussed. Second, the applications of this novel reaction in the context of materials science, bioorthogonal chemistry, and total synthesis of natural products will be elaborated with selected recent examples. The challenges and opportunities of the iEDDA reaction will be highlighted to give more insight into its potential applications in many other research areas.     

聚羧酸系高性能超塑化剂的研究进展

聚羧酸系超塑化剂由含磺酸基团、羧酸基团、聚氧烷基烯基团等不饱和单体在引发剂作用下合成的梳型高分子类聚合物,具有掺量低、减水率高以及增强效果显著等优点,是高性能混凝土中不可缺少的组分。随着高分子合成化学和高分子设计理论不断取得新的进展,成为高性能超塑化剂领域的研究热点。本文综述了国内外聚羧酸系超塑化剂的最新研究概况,对聚羧酸系超塑化剂的合成及作用机理进行了探讨,介绍了聚羧酸系超塑化剂所面临的问题,并对未来研究与应用发展方向进行了预测。     

Transition Metals in the Synthesis and Functionalization of Indoles [New Synthesis Methods (72)]

The use of transition-metal complexes as reagents for the synthesis of complex organic compounds has been under development for at least several decades, and many extraordinary organic transformations of profound potential have been realized. However, adoption of this chemistry by the practicing synthetic organic chemist has been inordinately slow, and only now are transition-metal reagents beginning to achieve their rightful place in the arsenal of organic synthesis. Several factors contributed to the initial reluctance of synthetic organic chemists to use organometallic reagents. Lacking education and experience in the ways of elements having d electrons, synthetic chemists viewed organometallic processes as something mysterious and unpredictable, and not to be discussed in polite society. Organometallic chemists did not help matters by advertising their latest advances as useful synthetic methodology, but restricting their studies to very simple organic systems lacking any serious functionality (e.g., the “methyl, ethyl, butyl, futile” syndrome). Happily, things have changed. Organometallic chemists have turned their attention to more complex systems, and more recently trained organic chemists have benefited from exposure to the application of transition metals. This combination has set the stage for major advances in the use of transition metals in the synthesis of complex organic compounds. This review deals with one aspect of this area, the use of transition metals in the synthesis of indoles.     

A Biocompatible Alkene Hydrogenation Merges Organic Synthesis with Microbial Metabolism

Organic chemists and metabolic engineers use orthogonal technologies to construct essential small molecules such as pharmaceuticals and commodity chemicals. While chemists have leveraged the unique capabilities of biological catalysts for small‐molecule production, metabolic engineers have not likewise integrated reactions from organic synthesis with the metabolism of living organisms. Reported herein is a method for alkene hydrogenation which utilizes a palladium catalyst and hydrogen gas generated directly by a living microorganism. This biocompatible transformation, which requires both catalyst and microbe, and can be used on a preparative scale, represents a new strategy for chemical synthesis that combines organic chemistry and metabolic engineering.     

Rapid Vortex Fluidics: Continuous Flow Synthesis of Amides and Local Anesthetic Lidocaine

Thin film flow chemistry using a vortex fluidic device (VFD) is effective in the scalable acylation of amines under shear, with the yields of the amides dramatically enhanced relative to traditional batch techniques. The optimized monophasic flow conditions are effective in ≤80 seconds at room temperature, enabling access to structurally diverse amides, functionalized amino acids and substituted ureas on multigram scales. Amide synthesis under flow was also extended to a total synthesis of local anesthetic lidocaine, with sequential reactions carried out in two serially linked VFD units. The synthesis could also be executed in a single VFD, in which the tandem reactions involve reagent delivery at different positions along the rapidly rotating tube with in situ solvent replacement, as a molecular assembly line process. This further highlights the versatility of the VFD in organic synthesis, as does the finding of a remarkably efficient debenzylation of p‐methoxybenzyl amines.     

Modern Electrochemical Aspects for the Synthesis of Value‐Added Organic Products

The use of electricity instead of stoichiometric amounts of oxidizers or reducing agents in synthesis is very appealing for economic and ecological reasons, and represents a major driving force for research efforts in this area. To use electron transfer at the electrode for a successful transformation in organic synthesis, the intermediate radical (cation/anion) has to be stabilized. Its combination with other approaches in organic chemistry or concepts of contemporary synthesis allows the establishment of powerful synthetic methods. The aim in the 21st Century will be to use as little fossil carbon as possible and, for this reason, the use of renewable sources is becoming increasingly important. The direct conversion of renewables, which have previously mainly been incinerated, is of increasing interest. This Review surveys many of the recent seminal important developments which will determine the future of this dynamic emerging field.     

New Generation of Biocatalysts for Organic Synthesis

The use of enzymes as catalysts for the preparation of novel compounds has received steadily increasing attention over the past few years. High demands are placed on the identification of new biocatalysts for organic synthesis. The catalysis of more ambitious reactions reflects the high expectations of this field of research. Enzymes play an increasingly important role as biocatalysts in the synthesis of key intermediates for the pharmaceutical and chemical industry, and new enzymatic technologies and processes have been established. Enzymes are an important part of the spectrum of catalysts available for synthetic chemistry. The advantages and applications of the most recent and attractive biocatalysts—reductases, transaminases, ammonia lyases, epoxide hydrolases, and dehalogenases—will be discussed herein and exemplified by the syntheses of interesting compounds.