Modulation of Prins Cyclization by Vibrational Strong Coupling

Light‐molecule strong coupling has emerged within the last decade as a new method to control chemical reactions. A few years ago it was discovered that chemical reactivity could be altered by vibrational strong coupling (VSC). Only a limited number of reactions have been investigated under VSC to date, including solvolysis and deprotection reactions. Here the effect of VSC on a series of aldehydes and ketones undergoing Prins cyclization, an important synthetic step in pharmaceutical chemistry, is investigated. A decrease of the second‐order rate constant with VSC of the reactant carbonyl stretching groups is observed. We also observe an increased activation energy due to VSC, but proportional changes in activation enthalpy and entropy, suggesting no substantive change in reaction pathway. The addition of common cycloaddition reactions to the stable of VSC‐modified chemical reactions is another step towards establishing VSC as a genuine tool for synthetic chemistry.     

Solvent Dependence on Cooperative Vibrational Strong Coupling and Cavity Catalysis**

Strong light-matter coupling offers a unique way to control chemical reactions at the molecular level. Here, we compare the solvent effect on an ester solvolysis process under cooperative vibrational strong coupling (VSC). Three reactants, para-nitrophenylacetate, 3-methyl-para-nitrophenylbenzoate, and bis-(2, 4-dinitrophenyl) oxalate are chosen to study the effect of VSC on the solvolysis reaction rates. Two solvents, ethyl acetate and cyclopentanone, are also considered to compare the cavity catalysis by coupling the C=O stretching band of the reactant and the solvent molecules to a Fabry-Perot cavity mode. Interestingly, both solvents enhance the chemical reaction rate of para-nitrophenylacetate and 3-methyl-para-nitrophenylbenzoate under cooperative VSC conditions. However, the resonance effect is observed at different temperatures for different solvents, which is further confirmed by thermodynamic studies. Bis-(2, 4-dinitrophenyl) oxalate doesn′t respond to VSC in either of the solvent systems due to poor overlap of reactant and solvent C=O vibrational bands. Cavity detuning and other control experiments suggest that cooperative VSC of the solvent plays a crucial role in modifying the activation free-energy of the reaction. These findings, along with other observations, cement the concept of polaritonic chemistry.     

Autotuning of Vibrational Strong Coupling for Site-Selective Reactions

Site-selective chemistry opens new paths for the synthesis of technologically important molecules. When a reactant is placed inside a Fabry–Perot (FP) cavity, energy exchange between molecular vibrations and resonant cavity photons results in vibrational strong coupling (VSC). VSC has recently been implicated in modified chemical reactivity at specific reactive sites. However, as a reaction proceeds inside an FP cavity, the refractive index of the reaction solution changes, detuning the cavity mode away from the vibrational mode and weakening the VSC effect. Here we overcome this issue, developing actuatable FP cavities to allow automated tuning of cavity mode energy to maintain maximized VSC during a reaction. As an example, the site-selective reaction of the aldehyde over the ketone in 4-acetylbenzaldehyde is achieved by automated cavity tuning to maintain optimal VSC of the ketone carbonyl stretch during the reaction. A nearly 50 % improvement in site-selective reactivity is observed compared to an FP cavity with static mirrors, demonstrating the utility of actuatable FP cavities as microreactors for organic chemistry.     

Trapping σ‐Alkyl–Palladium(II) Intermediates with Arynes Encompassing Intramolecular C−H Activation: Spirobiaryls through Pd‐Catalyzed Cascade Reactions

A palladium‐catalyzed cascade reaction based on the trapping of transient alkyl–Pd^II intermediates with arynes encompassing a C?H activation step has been developed. This synthetic pathway gives rise to hetero‐spirocyclic scaffolds containing a biaryl motif, and opens up new synthetic strategies in the design of cascade reactions since it gathers several aspects of Pd chemistry, i.e., intra‐ and intermolecular carbopalladation of unsaturated species, C?H activation and C?C coupling processes.     

Modification of Enzyme Activity by Vibrational Strong Coupling of Water

Vibrational strong coupling (VSC) has recently emerged as a completely new tool for influencing chemical reactivity. It harnesses electromagnetic vacuum fluctuations through the creation of hybrid states of light and matter, called polaritonic states, in an optical cavity resonant to a molecular absorption band. Here, we investigate the effect of vibrational strong coupling of water on the enzymatic activity of pepsin, where a water molecule is directly involved in the enzyme's chemical mechanism. We observe an approximately 4.5‐fold decrease of the apparent second‐order rate constant k_cat/K_m when coupling the water stretching vibration, whereas no effect was detected for the strong coupling of the bending vibration. The possibility of modifying enzymatic activity by coupling water demonstrates the potential of VSC as a new tool to study biochemical reactivity.     

Cavity Catalysis by Cooperative Vibrational Strong Coupling of Reactant and Solvent Molecules

Here, we report the catalytic effect of vibrational strong coupling (VSC) on the solvolysis of para‐nitrophenyl acetate (PNPA), which increases the reaction rate by an order of magnitude. This is observed when the microfluidic Fabry–Perot cavity in which the VSC is generated is tuned to the C=O vibrational stretching mode of both the reactant and solvent molecules. Thermodynamic experiments confirm the catalytic nature of VSC in the system. The change in the reaction rate follows an exponential relation with respect to the coupling strength of the solvent, indicating a cooperative effect between the solvent molecules and the reactant. Furthermore, the study of the solvent kinetic isotope effect clearly shows that the vibrational overlap of the C=O vibrational bands of the reactant and the strongly coupled solvent molecules is critical for the catalysis in this reaction. The combination of cooperative effects and cavity catalysis confirms the potential of VSC as a new frontier in chemistry.     

On‐Surface Bottom‐Up Synthesis of Azine Derivatives Displaying Strong Acceptor Behavior

On‐surface synthesis is an emerging approach to obtain, in a single step, precisely defined chemical species that cannot be obtained by other synthetic routes. The control of the electronic structure of organic/metal interfaces is crucial for defining the performance of many optoelectronic devices. A facile on‐surface chemistry route has now been used to synthesize the strong electron‐acceptor organic molecule quinoneazine directly on a Cu(110) surface, via thermally activated covalent coupling of para‐aminophenol precursors. The mechanism is described using a combination of in situ surface characterization techniques and theoretical methods. Owing to a strong surface‐molecule interaction, the quinoneazine molecule accommodates 1.2 electrons at its carbonyl ends, inducing an intramolecular charge redistribution and leading to partial conjugation of the rings, conferring azo‐character at the nitrogen sites.     

Microreaction Technology for Synthetic Chemistry

Microreaction technology as an emerging tool for synthetic chemistry has been extensively applied in academic and industrial researches. Normally, synthetic chemists used to running reactions in the classical glassware for centuries are unfamiliar and unaccustomed to use microreaction technology for routine synthetic work. This review tries to give a general introduction of the capabilities of microreaction technology. After introducing the origin and history of microreaction technology, we review and discuss mainly several synthetic examples of high T‐P reactions, hazardous reactions, flash chemistry, polymerization, photochemistry, electrochemistry and multistep API's syntheses to demonstrate the capabilities of microreactors. A summary and perspectives on microreactor technology are also given in this paper. It is anticipated that more and more chemists will understand the capabilities and limitations of microreaction technology, and could work together with chemical engineers for the synergic development of chemistry and chemical engineering.     

金催化的环化反应与钯催化的炔醇偶联/环化反应相结合用于合成多取代呋喃衍生物:串联反应的应用范围(英文)

开发了一种由金和钯催化π-活化由炔醇合成呋喃衍生物的集成方法.该合成策略是最显著的特点适用于带环辛基的底物,其适用范围比之前报道的有很大扩展.在Sonogashira反应条件下,由相应底物可直接得到环辛基呋喃.Pd在这些反应中起到2个重要作用:底物发生偶联反应的关键催化剂;通过π-活化促进炔醇中间体成环反应.该方法在一步合成3-碘呋喃反应中作用很突出,使通过偶联法进一步官能团化成为可能.我们还将AuBr_3用于多米诺成环/C-H键活化反应和无环前体的成环反应.本文结果表明,在该类成环反应中金和钯催化剂相辅相成.     

Dehydroaromatization of quinoxalines: one-step syntheses of trinuclear 1,6,7,12,13,18-hexaazatrinaphthylene titanium complexes

We report the spontaneous coupling of N-heterocycles, initiated by C-H bond activation reactions. The reaction of quinoxalines and the titanocene acetylene complex Cp2Ti{eta2-C2(SiMe3)2}, as an excellent titanocene source, results in the formation of trinuclear 1,6,7,12,13,18-hexaazatrinaphthylene (HATN) titanium complexes. These HATN titanium complexes are thermally stable but sensitive to air and moisture. A three-fold dehydrogenative C-C coupling is proposed as the main step in the presented synthetic procedure. Particularly using commercial starting materials, an efficient route for the dehydrogenative coupling of N-heterocycles, leading to multidentate ligands, has been established.     

光/电化学氧化诱导C–H键官能团化

C–H键活化及其官能团化一直被认为是合成化学的圣杯,光/电氧化诱导C–H键官能团化反应为追求更为绿色、原子经济性、步骤经济性更高的现代合成化学提供了新思路.我们借助可见光或电化学氧化诱导策略实现了直接C–H键官能团化,即底物无需预官能团化,无需外加氧化剂,可直接实现碳–碳以及碳–杂键的构建.通过光/电化学氧化诱导策略使得反应在更为温和的条件下进行,能够兼容更多官能团,并且为合成化学提供一条新的途径.近些年,该策略已经应用于不同化学环境C–H官能团化构建多种化学键.本文结合该领域的代表性工作,重点介绍本课题组近些年在光/电氧化诱导C–H键官能团化反应上的研究进展,并对这一领域的前景进行了展望.     

On the Role of Symmetry in Vibrational Strong Coupling: The Case of Charge-Transfer Complexation

It is well known that symmetry plays a key role in chemical reactivity. Here we explore its role in vibrational strong coupling (VSC) for a charge-transfer (CT) complexation reaction. By studying the trimethylated-benzene–I₂ CT complex, we find that VSC induces large changes in the equilibrium constant K_DA of the CT complex, reflecting modifications in the ΔG° value of the reaction. Furthermore, by tuning the microfluidic cavity modes to the different IR vibrations of the trimethylated benzene, ΔG° either increases or decreases depending only on the symmetry of the normal mode that is coupled. This result reveals the critical role of symmetry in VSC and, in turn, provides an explanation for why the magnitude of chemical changes induced by VSC are much greater than the Rabi splitting, that is, the energy perturbation caused by VSC. These findings further confirm that VSC is powerful and versatile tool for the molecular sciences.     

Oxidation‐Induced C—H Functionalization: A Formal Way for C—H Activation

Cross‐coupling reactions have developed widely and provided a powerful means to synthesize a variety of compounds in each chemical field. The compounds which have C—H bonds are widespread in fossil fuels, chemical raw materials, biologically active molecules, etc. Using these readily‐ available substances as substrates is high atom‐ and step‐economy for cross‐coupling reactions. Over the past decades, our research group focused on finding and developing new strategies for C—H functionalization. Compared with classical C—H activation methods, for example, C—H bonds are deprotonated by strong base or converted into C—M bonds, oxidation‐induced C—H functionalization would be another pathway for C—H bond activation. This perspective shows a brief introduction of our recent works in this oxidation‐induced C—H functionalization. We categorized this approach of these C—H bond activations by the key intermediates, radical cations, radicals and cations.     

Chemical Oscillations

Under constant external conditions, chemical reactions may also proceed in a rhythmic manner. The kinetic mechanisms responsible for such oscillations prove to be unexpectedly complicated. It can nevertheless be demonstrated that chemical periodicity is caused by certain kinds of coupling between simultaneous reactions or transport processes. A general survey of the chemistry and phenomenology of the principal chemical oscillations is followed by a discussion of the situations leading to periodic reactions on the basis of the multivariable kinetics of feedback systems. Autocatalysis and autoinhibition play an important role, as also do kinetic instability and spatial propagation.     

On the Role of Symmetry in Vibrational Strong Coupling: The Case of Charge‐Transfer Complexation

It is well known that symmetry plays a key role in chemical reactivity. Here we explore its role in vibrational strong coupling (VSC) for a charge‐transfer (CT) complexation reaction. By studying the trimethylated‐benzene–I₂ CT complex, we find that VSC induces large changes in the equilibrium constant K_DA of the CT complex, reflecting modifications in the ΔG° value of the reaction. Furthermore, by tuning the microfluidic cavity modes to the different IR vibrations of the trimethylated benzene, ΔG° either increases or decreases depending only on the symmetry of the normal mode that is coupled. This result reveals the critical role of symmetry in VSC and, in turn, provides an explanation for why the magnitude of chemical changes induced by VSC are much greater than the Rabi splitting, that is, the energy perturbation caused by VSC. These findings further confirm that VSC is powerful and versatile tool for the molecular sciences.     

Encrypting Chemical Reactivity in Protein Sequences toward Information‐Coded Reactions†

Controlling chemical reactivity has been the central theme in chemistry. Herein, we review the recent progress on the development of genetically encoded protein coupling reactions and their potential applications. The chemical reactivity is encoded in the protein sequences. The information is read out by folding and molecular recognition between two reactive components and subsequently translated into chemical bonding via autocatalysis. It has emerged as a unique way to tune the chemical reactivity and is regarded as one type of information‐coded reactions. Not only has it received many applications such as protein topology engineering, bioconjugation, biomaterials and synthetic biology, but also its principle may be extended beyond protein chemistry to enable new modes of supramolecular interactions that promote chemical bonding and that are simultaneously reinforced by covalent bonds.     

The Increasing Value of Biomass: Moving From C6 Carbohydrates to Multifunctionalized Building Blocks via 5-(hydroxymethyl)furfural

Recent decades have been marked by enormous progress in the field of synthesis and chemistry of 5-(hydroxymethyl)furfural (HMF), an important platform chemical widely recognized as the “sleeping giant” of sustainable chemistry. This multifunctional furanic compound is viewed as a strong link for the transition from the current fossil-based industry to a sustainable one. However, the low chemical stability of HMF significantly undermines its synthetic potential. A possible solution to this problem is synthetic diversification of HMF by modifying it into more stable multifunctional building blocks for further synthetic purposes.     

N-heterocyclic carbene catalyzed domino reactions

While organocatalyzed domino reactions or "organocascade catalysis" developed into an important tool in synthetic chemistry during the past decade, the utility of N-heterocyclic carbenes (NHCs) as catalysts in domino reactions has only received growing attention in the past three years. Taking into account the unique activation modes of the substrates by NHC catalysts, it is often difficult to distinguish between a single chemical transformation and a sequential one-pot transformation. Therefore, herein we present a critical consideration of domino, cascade, and tandem catalysis in the case of NHC catalysts and highlight recent publications in this area.     

Protein Film Voltammetry: Revealing the Mechanisms of Biological Oxidation and Reduction

One of the most intriguing and important aspects of biological chemistry is how the deceptively simple process of electron transfer (ET) is utilized and organized by macromolecules that perform some of the most sophisticated chemistry known to man. The fundamental principles of ET are now fairly well understood, and interest is being focused instead on the mechanisms by which ET in proteins is coupled to chemical reactions such as ion transport and catalysis. Protein film voltammetry provides a powerful way to investigate these problems. The protein is immobilized on an electrode as an absorbed electroactive film and by applying a potential, electrons are driven in and out of the active sites. Signals are obtained from extremely small sample quantities (monolayer coverage or less), and from these it is possible to detect and characterize active sites and to resolve complex reactions. Experiments may be carried out over a wide dynamic range: for example, with cyclic voltammetry scan rates exceeding 1000 V/s can be used to observe coupling reactions that occur in the sub-millisecond time domain. For enzymes, fast cycles can be used to trap intermediates; alternatively steady-state catalysis and redox-linked activation can be studied using slow scan rates or potential step methods. This paper explains the concept of protein film voltammetry and illustrates how it can be applied to some complex problems in biological redox chemistry.     

Photochemical C–N bond forming reactions for the synthesis of five-membered fused N-heterocycles

Abstract

Few conversions cannot take place with ground-state reactions even with the help of a catalyst, therefore they are made to occur under photochemical conditions. The transfer of electrons took place even with the photochemical excitement of one molecule where redox reaction cannot occur at the ground state. The ground-state reactions resulted in the formation of side products. The substrates did not require any sort of chemical activation for C–N bond construction in the course of photochemical reactions. The source of energy; light has always been the interest of researchers in order to induce chemical reactions ever since the starting of scientific chemistry. The present review encloses the chemistry of photochemical transformations with a focus on their synthetic uses. The organic photochemical reactions prevent the polluting or harmful reagents thus, provides a possibility for sustainable procedures as well as green chemistry. This review article displays the formation of numerous of five-membered fused nitrogen-heterocyclic compounds.