The late stage functionalization (LSF) of complex biorelevant compounds is a powerful tool to speed up the identification of structure-activity relationships (SARs) and to optimize ADME profiles. To this end, visible-light photocatalysis offers unique opportunities to achieve smooth and clean functionalization of drugs by unlocking site-specific reactivities under generally mild reaction conditions. This review offers a critical assessment of current literature, pointing out the recent developments in the field while emphasizing the expected future progress and potential applications. Along with paragraphs discussing the visible-light photocatalytic synthetic protocols so far available for LSF of drugs and drug candidates, useful and readily accessible synoptic tables of such transformations, divided by functional groups, will be provided, thus enabling a useful, fast, and easy reference to them.

Visible light photocatalysis in the late-stage functionalization of pharmaceutically relevant compounds.

Cross-coupling reaction between two C–H bonds has become a fundamental strategy in synthetic organic chemistry. With its increasing importance in green chemistry, atom economy, and step economy, it...

En Route to Intermolecular Cross-Dehydrogenative Coupling Reactions.

Organic compounds that show Thermally Activated Delayed Fluorescence (TADF) have become wildly popular as next-generation emitters in organic light emitting diodes (OLEDs). Since 2016, a subset of these have found increasing use as photocatalysts. This review comprehensively highlights their potential by documenting the diversity of the reactions where an organic TADF photocatalyst can be used in lieu of a noble metal complex photocatalyst. Beyond the small number of TADF photocatalysts that have been used to date, the analysis conducted within this review reveals the wider potential of organic donor–acceptor TADF compounds as photocatalysts. A discussion of the benefits of compounds showing TADF for photocatalysis is presented, which paints a picture of a very promising future for organic photocatalyst development.

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Organic thermally activated delayed fluorescence (TADF) compounds used in photocatalysis

Alkylation of arenes is one of the most fundamental transformations in chemical synthesis and leads to privileged scaffolds in many areas of science. Classical methods for the introduction of alkyl groups to arenes are mostly based on the Friedel-Crafts reaction, radical additions, metalation, or prefunctionalization of the arene: these methods, however, suffer from limitations in scope, efficiency, and selectivity. Moreover, they are based on the innate reactivity of the starting arene, favoring the alkylation at a certain position and rendering the introduction of alkyl chains at other positions much more challenging. This can be addressed by the use of a directing group that facilitates, in the presence of a metal catalyst, the regioselective alkylation of a C-H bond. These directed alkylations of C-H bonds in arenes will be comprehensively summarized in this Review.

Beyond Friedel and Crafts: Directed Alkylation of C-H Bonds in Arenes.

The highly regioselective electrophotocatalytic C–H functionalization of ethers is described. These reactions are catalyzed by a trisaminocyclopropenium (TAC) ion at mild electrochemical potential ...

Electrophotocatalytic C-H Functionalization of Ethers with High Regioselectivity.

An important challenge in the Cα-heteroarylation of ethers is the requirement of a large excess amount of ethers (that are used as solvents in many cases) to achieve effective transformations. This drawback has significantly restricted the Cα-heteroarylation of ethers to the use of simple and easily accessible ether substrates. To overcome this limitation, a new, efficient, N-hydroxysuccinimide (NHS) mediated, mild and metal-free CDC strategy for the direct Cα-heteroarylation of diverse ethers has been developed. Different to our previous benzaldehyde mediated photoredox Cα-heteroarylation, we have identified NHS as a new and efficient mediator without using light. A distinct non-photoredox engaged hydrogen-atom-transfer (HAT) mechanism that used a nitrogen-centered radical cation produced from NHS is initially revealed. Notably, only 5–10 equivalents of ethers as coupling partners are used, which allows for structurally diverse and complex ethers to engage in this process, to create highly medicinally relevant Cα-heteroarylated ethers. Furthermore, more structurally diverse heterocyclics can serve as reactants for this process.

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Direct Cα-heteroarylation of structurally diverse ethers via a mild N-hydroxysuccinimide mediated cross-dehydrogenative coupling reaction.

Failure analysis of the boiler water-wall tube

The efficient and selective C-H silylation of heteroarenes, especially the pharmaceutically relevant electron-deficient heteroarenes, represents a great challenge in organic synthesis. Herein we wish to report a distinctive visible light-promoted photocatalytic C-H silylation approach that enables the direct coupling of trialkylhydrosilanes with both electron-deficient and -rich heteroarenes as well as with cyano-substituted arenes in moderate to high yields and with good regioselectivity. The protocol features operational simplicity, mild reaction conditions, and the use of safe and readily available Na2S2O8, bis(trimethylsilyl) peroxide (BTMSPO) or iPr3SiSH as the radical initiators. Notably, the challenging bulky and inert trialkylhydrosilanes, such as (t-butyldimethyl)silane ( t BuMe2SiH) and (triisopropyl)silane (iPr3SiH), work smoothly with the protocol. Moreover, despite the higher stability of t BuMe2Si silylation products, our studies revealed their great reactivity and versatility in diverse C-Si-based chemical transformations, providing an operationally simple, low-cost, and environmentally benign synthetic technology for molecule construction and elaboration.

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Shihui Liu

Papers

Direct Cα-heteroarylation of structurally diverse ethers via a mild N-hydroxysuccinimide mediated cross-dehydrogenative coupling reaction.

Failure analysis of the boiler water-wall tube

Photocatalytic C–H silylation of heteroarenes by using trialkylhydrosilanes

Highly stereoselective synthesis of aryl/heteroaryl-C-nucleosides via the merger of photoredox and nickel catalysis

Graphitic Carbon Nitride Polymer as a Recyclable Photoredox Catalyst for Decarboxylative Alkynylation of Carboxylic Acids