Transition-Metal-Catalyzed C-H Bond Activation for the Formation of C-C Bonds in Complex Molecules.

Site-predictable and chemoselective C-H bond functionalization reactions offer synthetically powerful strategies for the step-economic diversification of both feedstock and fine chemicals. Many transition-metal-catalyzed methods have emerged for the selective activation and functionalization of C-H bonds. However, challenges of regio- and chemoselectivity have emerged with application to highly complex molecules bearing significant functional group density and diversity. As molecular complexity increases within molecular structures the risks of catalyst intolerance and limited applicability grow with the number of functional groups and potentially Lewis basic heteroatoms. Given the abundance of C-H bonds within highly complex and already diversified molecules such as pharmaceuticals, natural products, and materials, design and selection of reaction conditions and tolerant catalysts has proved critical for successful direct functionalization. As such, innovations within transition-metal-catalyzed C-H bond functionalization for the direct formation of carbon-carbon bonds have been discovered and developed to overcome these challenges and limitations. This review highlights progress made for the direct metal-catalyzed C-C bond forming reactions including alkylation, methylation, arylation, and olefination of C-H bonds within complex targets.

Graphitic Carbon Nitride as a Photocatalyst for Decarboxylative C(sp2)-C(sp3) Couplings via Nickel Catalysis.

The development of robust and reliable methods for the construction of C(sp2)-C(sp3) bonds is vital for accessing an increased array of structurally diverse scaffolds in drug discovery and development campaigns. While significant advances towards this goal have been achieved using metallaphotoredox chemistry, many of these methods utilise photocatalysts based on precious-metals due to their efficient redox processes and tuneable properties. However, due to the cost, scarcity, and toxicity of these metals, the search for suitable replacements should be a priority. Here, we show the use of commercially available heterogeneous semiconductor graphitic carbon nitride (gCN) as a photocatalyst, combined with nickel catalysis, for the cross-coupling between aryl halide and carboxylic acid coupling partners. gCN has been shown to engage in single-electron-transfer (SET) and energy-transfer (EnT) processes for the formation of C-X bonds, and in this manuscript we overcome previous limitations to furnish C-C over C-O bonds using carboxylic acids. A broad scope of both aryl halides and carboxylic acids is presented, and recycling of the photocatalyst demonstrated. The mechanism of the reaction is also investigated.

Improving the sustainability of the ruthenium-catalysed N-directed C-H arylation of arenes with aryl halides.

Direct C-H functionalisation methodologies represent an opportunity to improve the overall 'green' credentials of organic coupling reactions, improving atom economy and reducing overall step count. Despite this, these reactions frequently run under reaction conditions that leave room for improved sustainability. Herein, we describe a recent advance in our ruthenium-catalysed C-H arylation methodology that aims to address some of the environmental impacts associated with this procedure, including solvent choice, reaction temperature, reaction time, and loading of the ruthenium catalyst. We believe that our findings demonstrate a reaction with improved environmental credentials and showcase it on a multi-gram scale within an industrial setting.

Catalysis with cycloruthenated complexes.

Cycloruthenated complexes have been studied extensively over the last few decades. Many accounts of their synthesis, characterisation, and catalytic activity in a wide variety of transformations have been reported to date. Compared with their non-cyclometallated analogues, cycloruthenated complexes may display enhanced catalytic activities in known transformations or possess entirely new reactivity. In other instances, these complexes can be chiral, and capable of catalysing stereoselective reactions. In this review, we aim to highlight the catalytic applications of cycloruthenated complexes in organic synthesis, emphasising the recent advancements in this field.