Selective C(sp2)−H Halogenation of "click" 4-Aryl-1,2,3-triazoles

Selective bromination reactions of “click compounds” are described. Electron-neutral and electron-deficient arenes selectively undergo unprecedented Pd-catalyzed C–H ortho-halogenations assisted by simple triazoles as modular directing groups, whereas electron-rich arenes are regioselectively halogenated following an electrophilic aromatic substitution reaction pathway. These C–H halogenation procedures exhibit a wide group tolerance, complement existing bromination procedures, and represent versatile synthetic tools of utmost importance for the late-stage diversification of “click compounds”. The characterization of a triazole-containing palladacycle and density functional theory studies supported the mechanism proposal.We are grateful to Gobierno Vasco (ELKARTEK_KK-2015/0000101; IT_1033-16) and UPV/EHU (GIU15/31) for financial support. A. C. thanks MINECO for a Ramón y Cajal research contract (RYC-2012-09873). Cost-CHAOS action is also acknowledged

Insights into enzymatic halogenation from computational studies

The halogenases are a group of enzymes that have only come to the fore over the last 10 years thanks to the discovery and characterization of several novel representatives. They have revealed the fascinating variety of distinct chemical mechanisms that nature utilizes to activate halogens and introduce them into organic substrates. Computational studies using a range of approaches have already elucidated many details of the mechanisms of these enzymes, often in synergistic combination with experiment. This Review summarizes the main insights gained from these studies. It also seeks to identify open questions that are amenable to computational investigations. The studies discussed herein serve to illustrate some of the limitations of the current computational approaches and the challenges encountered in computational mechanistic enzymology

Enzymatic functionalization of carbon-hydrogen bonds

The development of new catalytic methods to functionalize carbon–hydrogen (C–H) bonds continues to progress at a rapid pace due to the significant economic and environmental benefits of these transformations over traditional synthetic methods. In nature, enzymes catalyze regio- and stereoselective C–H bond functionalization using transformations ranging from hydroxylation to hydroalkylation under ambient reaction conditions. The efficiency of these enzymes relative to analogous chemical processes has led to their increased use as biocatalysts in preparative and industrial applications. Furthermore, unlike small molecule catalysts, enzymes can be systematically optimized via directed evolution for a particular application and can be expressed in vivo to augment the biosynthetic capability of living organisms. While a variety of technical challenges must still be overcome for practical application of many enzymes for C–H bond functionalization, continued research on natural enzymes and on novel artificial metalloenzymes will lead to improved synthetic processes for efficient synthesis of complex molecules. In this critical review, we discuss the most prevalent mechanistic strategies used by enzymes to functionalize non-acidic C–H bonds, the application and evolution of these enzymes for chemical synthesis, and a number of potential biosynthetic capabilities uniquely enabled by these powerful catalysts (110 references)

Functionalization of Pyrene To Prepare Luminescent Materials—Typical Examples of Synthetic Methodology

Pyrene-based π-conjugated materials are considered to be an ideal organic electro-luminescence material for application in semiconductor devices, such as organic light-emitting diodes (OLEDs), organic field-effect transistors (OFETs) and organic photovoltaics (OPVs), and so forth. However, the great drawback of employing pyrene as an organic luminescence material is the formation of excimer emission, which quenches the efficiency at high concentration or in the solid-state. Thus, in order to obtain highly efficient optical devices, scientists have devoted much effort to tuning the structure of pyrene derivatives in order to realize exploitable properties by employing two strategies, 1) introducing a variety of moieties at the pyrene core, and 2) exploring effective and convenient synthetic strategies to functionalize the pyrene core. Over the past decades, our group has mainly focused on synthetic methodologies for functionalization of the pyrene core; we have found that formylation/acetylation or bromination of pyrene can selectly lead to functionalization at K-region by Lewis acid catalysis. Herein, this Minireview highlights the direct synthetic approaches (such as formylation, bromination, oxidation, and de-tert-butylation reactions, etc.) to functionalize the pyrene in order to advance research on luminescent materials for organic electronic applications. Further, this article demonstrates that the future direction of pyrene chemistry is asymmetric functionalization of pyrene for organic semiconductor applications and highlights some of the classical asymmetric pyrenes, as well as the latest breakthroughs. In addition, the photophysical properties of pyrene-based molecules are briefly reviewed. To give a current overview of the development of pyrene chemistry, the review selectively covers some of the latest reports and concepts from the period covering late 2011 to the present day

Halogenases:a palette of emerging opportunities for synthetic biology–synthetic chemistry and C–H functionalisation

The enzymatic generation of carbon–halogen bonds is a powerful strategy used by both nature and synthetic chemists to tune the bioactivity, bioavailability and reactivity of compounds, opening up the opportunity for selective C–H functionalisation. Genes encoding halogenase enzymes have recently been shown to transcend all kingdoms of life. These enzymes install halogen atoms into aromatic and less activated aliphatic substrates, achieving selectivities that are often challenging to accomplish using synthetic methodologies. Significant advances in both halogenase discovery and engineering have provided a toolbox of enzymes, enabling the ready use of these catalysts in biotransformations, synthetic biology, and in combination with chemical catalysis to enable late stage C–H functionalisation. With a focus on substrate scope, this review outlines the mechanisms employed by the major classes of halogenases, while in parallel, it highlights key advances in the utilisation of the combination of enzymatic halogenation and chemical catalysis for C–H activation and diversification

Catalytic electrophilic halogenation of silyl-protected and terminal alkynes: trapping gold(I) acetylides vs. a bronsted acid-promoted reaction

In the presence of a cationic gold(I) catalyst and N-halosuccinimide, both trimethylsilyl-protected and terminal alkynes are converted into alkynyl halides. Further experiments showed that silyl-protected alkynes undergo electrophilic iodination and bromination under Brønsted acid catalysis, whilst terminal alkynes require a cationic gold catalyst. The former reactions probably proceed via activation of the electrophile, whilst the latter reactions proceed via a gold(I) acetylide intermediate. Gold-catalysed halogenation was further combined with gold-catalysed hydration and subsequent annulation to provide convenient routes to iodomethyl ketones and five-membered aromatic heterocycles

Halo acids and DMSO: Electrophilic aromatic substitution at room temperature conditions

A simple, safe and cost effective experiment to demonstrate electrophilic aromatic substitution in the undergraduate laboratory can be accomplished by placing a small amount of N,N Dimethyl Aniline or a few crystals of Phenol in an NMR tube containing an appropriate level of deutero DMSO. After observation of the expanded proton NMR spectrum of the aromatic region, a few drops of concentrated HBr and HC1 aqueous acids are added and the NMR spectrum recorded after one hour. Observation of an A,A\u27 B,B\u27 typical four line pattern in the aromatic region of NMR spectrum is direct evidence for the halogenation on the aromatic ring at para position. Addition of gaseous hydrogen chloride provides a faster and cleaner reaction. A mechanism for the reaction, GC/MS data to support the NMR results, along with other examples are presented. Application of the reaction for halogenation of complex biomolecules in an attempt to enhance their activity is plausible because room temperature experimental conditions should prevent structural degradation of sensitive molecules and produce fewer non-toxic byproducts