Thermal C-C bond cleavage reactions allow the construction of structurally diverse molecular skeletons via predictable and efficient bond reorganizations. Visible light photoredox-catalyzed radical-mediated C-C bond cleavage reactions have recently emerged as a powerful alternative method for overcoming the thermodynamic and kinetic barrier of C-C bond cleavage in diverse molecular scaffolds. In recent years, a plethora of elegant and useful reactions have been invented, and the products are sometimes otherwise inaccessible by classic thermal reactions. Considering the great influence and synthetic potential of these reactions, we provide a summary of the state of art visible light-driven radical-mediated C-C bond cleavage/functionalization strategies with a specific emphasis on the working models. We hoped that this review will be useful for medicinal and synthetic organic chemists and will inspire further reaction development in this interesting area.

Visible Light-Driven Radical-Mediated C-C Bond Cleavage/Functionalization in Organic Synthesis

Direct photocatalyzed hydrogen atom transfer (d-HAT) can be considered a method of choice for the elaboration of aliphatic C-H bonds. In this manifold, a photocatalyst (PCHAT) exploits the energy of a photon to trigger the homolytic cleavage of such bonds in organic compounds. Selective C-H bond elaboration may be achieved by a judicious choice of the hydrogen abstractor (key parameters are the electronic character and the molecular structure), as well as reaction additives. Different are the classes of PCsHAT available, including aromatic ketones, xanthene dyes (Eosin Y), polyoxometalates, uranyl salts, a metal-oxo porphyrin and a tris(amino)cyclopropenium radical dication. The processes (mainly C-C bond formation) are in most cases carried out under mild conditions with the help of visible light. The aim of this review is to offer a comprehensive survey of the synthetic applications of photocatalyzed d-HAT.

Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C-H Bonds Elaboration

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.

The past decade has witnessed the emergence of N-(acyloxy)phthalimides (NHPI esters) and its derivatives at the forefront of synthetic methods facilitating the construction of diverse molecular fra...

Single Electron Transfer-Induced Redox Processes Involving N-(Acyloxy)phthalimides

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

Visible-Light-Mediated, Chemo- and Stereoselective Radical Process for the Synthesis of C-Glycoamino Acids.

Synthesis of Enantioenriched α-Deuterated α-Amino Acids Enabled by an Organophotocatalytic Radical Approach.

H/D exchange at formyl groups represents the straightforward approach to C-1 deuterated aldehydes. This transformation has been recently realized by transition metal and NHC carbene catalysis. Mech...

Deuteration of Formyl Groups via a Catalytic Radical H/D Exchange Approach

A metal- and oxidant-free catalytic method for accessing structurally diverse thioesters from readily accessible, widespread aldehydes, is described. A strategy of a simple organic 9,10-phenanthrenequinone-promoted hydrogen atom transfer (HAT) with visible light was successfully implemented to selectively generate acyl radicals without inducing crossover reactivity of thioester products. The preparative power of the method was demonstrated by broad substrate scope and wide functional group tolerance, and enabled the late-stage modification of complex structures, which are difficult to achieve with the existing protocols.

Yongyi Wei

Papers

Visible-Light-Mediated, Chemo- and Stereoselective Radical Process for the Synthesis of C-Glycoamino Acids.

Synthesis of Enantioenriched α-Deuterated α-Amino Acids Enabled by an Organophotocatalytic Radical Approach.

Deuteration of Formyl Groups via a Catalytic Radical H/D Exchange Approach

Organocatalytic Transformation of Aldehydes to Thioesters with Visible Light.