Electrochemical Ruthenium‐Catalysed Directed C−H Functionalization of Arenes with Boron Reagents

Ortho-directed electrochemical C−H functionalization of aromatics with boron-based coupling partners has been achieved under ruthenium catalysis through an oxidatively induced reductive elimination mechanism. Our method provides a single set of conditions delivering C−H arylation, alkenylation and methylation, yielding ortho-functionalized products with good functional group tolerance, including examples of late-stage functionalization in synthetically useful yields. By harnessing electricity as a ‘green’ oxidant, this method circumvents the need for stoichiometric quantities of chemical oxidants, enhancing our sustainability metrics

Direct ortho-Arylation of Pyridinecarboxylic Acids: Overcoming the Deactivating Effect of sp2-Nitrogen

Direct arylations of pyridines are challenging transformations due to the high Lewis basicity of the sp²-nitrogen. The use of carboxylates as directing groups is reported, facilitating the Pd-catalyzed C–H arylation of this difficult class of substrates. This methodology allows regioselective C3/C4 arylation, without the need to use solvent quantities of the pyridine, and using low-cost chloro- and bromoarenes as coupling partners. Furthermore, carboxylates could be employed as traceless directing groups through a one-pot C–H arylation/Cu­(I)-mediated decarboxylation sequence, thereby accessing directing-group-free pyridine biaryls

<i>meta</i>-Selective olefination of fluoroarenes with alkynes using CO₂ as a traceless directing group.

From Europe PMC via Jisc Publications RouterHistory: ppub 2020-03-01, epub 2020-03-31Publication status: PublishedFunder: Engineering and Physical Sciences Research Council; Grant(s): EP/L014017/2Over the last few decades C-H olefination has received significant interest, due to the importance and usefulness of aryl olefins both as synthetic targets and intermediates. While a wide range of ortho-olefination protocols have been developed, only a small number of meta-olefinations are currently available. Importantly, the most common approach to meta-olefination, using a large meta-directing template, is not suitable for substrates such as fluorobenzenes, which cannot be derivatised. We report that the meta-selective olefination of fluoroarenes can be achieved via the use of CO2 as a traceless directing group, which can be easily installed and removed in a one-pot process. Furthermore, this approach avoids the use of stoichiometric Ag(i)-salts, commonly used in C-H olefinations, and affords complete meta- over ortho/para-regioselectivity

Ruthenium-Catalyzed Mono-Selective C–H Methylation and d₃-Methylation of Arenes

[Image: see text] Site-selective installation of C–Me bonds remains a powerful and sought-after tool to alter the chemical and pharmacological properties of a molecule. Direct C–H functionalization provides an attractive means of achieving this transformation. Such protocols, however, typically utilize harsh conditions and hazardous methylating agents with poor applicability toward late-stage functionalization. Furthermore, highly monoselective methylation protocols remain scarce. Herein, we report an efficient monoselective, directed ortho-methylation of arenes using N,N,N-trimethylanilinium salts as noncarcinogenic, bench-stable methylating agents. We extend this protocol to d(3)-methylation in addition to the late-stage functionalization of pharmaceutically active compounds. Detailed kinetic studies indicate the rate-limiting in situ formation of MeI is integral to the observed reactivity

Palladium catalysed C-H arylation of pyrenes: access to a new class of exfoliating agents for water-based graphene dispersions.

From Europe PMC via Jisc Publications RouterHistory: ppub 2020-01-01, epub 2020-01-28Publication status: PublishedFunder: Engineering and Physical Sciences Research Council; Grant(s): 1781838, EP/P00119X/1A new and diverse family of pyrene derivatives was synthesised via palladium-catalysed C-H ortho-arylation of pyrene-1-carboxylic acid. The strategy affords easy access to a broad scope of 2-substituted and 1,2-disubstituted pyrenes. The C1-substituent can be easily transformed into carboxylic acid, iodide, alkynyl, aryl or alkyl functionalities. This approach gives access to arylated pyrene ammonium salts, which outperformed their non-arylated parent compound during aqueous Liquid Phase Exfoliation (LPE) of graphite and compare favourably to state-of-the-art sodium pyrene-1-sulfonate PS1. This allowed the production of concentrated and stable suspensions of graphene flakes in water

Ru-Catalyzed C-H Arylation of Fluoroarenes with Aryl Halides

We gratefully acknowledge the Engineering and Physical Sciences Research Council (EPSRC, EP/I038578/1 and EP/ K039547/1) for funding and the European Research Council for a Starting Grant (to I.L.).

Defect-free graphene enhances enzyme delivery to fibroblasts derived from patients with lysosomal storage disorders

Enzyme replacement therapy shows remarkable clinical improvement in treating lysosomal storage disorders. However, this therapeutic approach is hampered by limitations in the delivery of the enzyme to cells and tissues. Therefore, there is an urgent, unmet clinical need to develop new strategies to enhance the enzyme delivery to diseased cells. Graphene-based materials, due to their dimensionality and favourable pattern of interaction with cells, represent a promising platform for the loading and delivery of therapeutic cargo. Herein, the potential use of graphene-based materials, including defect-free graphene with positive or negative surface charge and graphene oxide with different lateral dimensions, was investigated for the delivery of lysosomal enzymes in fibroblasts derived from patients with Mucopolysaccharidosis VI and Pompe disease. We report excellent biocompatibility of all graphene-based materials up to a concentration of 100 μg mL in the cell lines studied. In addition, a noticeable difference in the uptake profile of the materials was observed. Neither type of graphene oxide was taken up by the cells to a significant extent. In contrast, the two types of graphene were efficiently taken up, localizing in the lysosomes. Furthermore, we demonstrate that cationic graphene flakes can be used as carriers for arylsulfatase B enzyme, for the delivery of the lacking enzyme to the lysosomes of Mucopolysaccharidosis VI fibroblasts. Arylsulfatase B complexed with cationic graphene flakes not only retained the enzymatic activity, but also exerted biological effects almost twice as high as arylsulfatase B alone in the clearance of the substrate in Mucopolysaccharidosis VI fibroblasts. This study lays the groundwork for the potential use of graphene-based materials as carriers for enzyme replacement therapy in lysosomal storage disorders