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

The association of an electron-rich substrate with an electron-accepting molecule can generate a new molecular aggregate in the ground state, called an electron donor–acceptor (EDA) complex. Even w...

https://pubs.acs.org/doi/pdf/10.1021/jacs.0c01416

Synthetic Methods Driven by the Photoactivity of Electron Donor-Acceptor Complexes

The merger of photoredox catalysis with transition metal catalysis, termed metallaphotoredox catalysis, has become a mainstay in synthetic methodology over the past decade. Metallaphotoredox catalysis has combined the unparalleled capacity of transition metal catalysis for bond formation with the broad utility of photoinduced electron- and energy-transfer processes. Photocatalytic substrate activation has allowed the engagement of simple starting materials in metal-mediated bond-forming processes. Moreover, electron or energy transfer directly with key organometallic intermediates has provided novel activation modes entirely complementary to traditional catalytic platforms. This Review details and contextualizes the advancements in molecule construction brought forth by metallaphotocatalysis.

Metallaphotoredox: The Merger of Photoredox and Transition Metal Catalysis.

Radical-radical couplings are mostly nearly diffusion-controlled processes. Therefore, the selective cross-coupling of two different radicals is challenging and not a synthetically valuable transformation. However, if the radicals have different lifetimes and if they are generated at equal rates, cross-coupling will become the dominant process. This high cross-selectivity is based on a kinetic phenomenon called the persistent radical effect (PRE). In this Review, an explanation of the PRE supported by simulations of simple model systems is provided. Radical stabilities are discussed within the context of their lifetimes, and various examples of PRE-mediated radical-radical couplings in synthesis are summarized. It is shown that the PRE is not restricted to the coupling of a persistent with a transient radical. If one coupling partner is longer-lived than the other transient radical, the PRE operates and high cross-selectivity is achieved. This important point expands the scope of PRE-mediated radical chemistry. The Review is divided into two parts, namely 1) the coupling of persistent or longer-lived organic radicals and 2) "radical-metal crossover reactions"; here, metal-centered radical species and more generally longer-lived transition-metal complexes that are able to react with radicals are discussed-a field that has flourished recently.

The Persistent Radical Effect in Organic Synthesis

Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles These reactions have proven particularly useful for the coupling of sec-alkyl electrophiles to form stereogenic centers; however, the development of enantioselective variants remains challenging In this Perspective, we summarize the progress that has been made toward Ni-catalyzed enantioselective reductive cross-coupling reactions

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Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions.

Highly regio- and enantioselective allylic alkylation has been achieved enabled by the merger of photoredox and palladium catalysis. In this dual catalytic process, alkyl radicals generated from 4-alkyl-1,4-dihydropyridines act as the coupling partners of the π-allyl palladium complexes. The generality of this method has been illustrated through the reaction of a variety of allyl esters with 4-alkyl-1,4-dihydropyridines. This mechanistically novel strategy expands the scope of the traditional Pd-catalyzed asymmetric allylic alkylation reaction and serves as its alternative and potential complement.

Enantioselective Allylic Alkylation with 4-Alkyl-1,4-dihydro-pyridines Enabled by Photoredox/Palladium Cocatalysis

Transition metal catalysis is one of the most important tools to construct carbon-carbon and carbon-heteroatom bonds in modern organic synthesis. Visible-light photoredox catalysis has recently drawn considerable attention of the scientific community owing to its unique activation modes and significance for the green synthesis. The merger of photoredox catalysis with transition metal catalysts, termed metallaphotoredox catalysis, has become a popular strategy for expanding the synthetic utility of visible-light photocatalysis. This strategy has led to the discovery of novel asymmetric transformations, which are unfeasible or not easily accessible by a single catalytic system. This contemporary area of organic chemistry holds promise for the development of economical and environmentally friendly methods for the asymmetric synthesis of chiral compounds. In this review, the advances in the enantioselective metallaphotoredox catalysis (EMPC) are summarized.

A review of enantioselective dual transition metal/photoredox catalysis

Enantioselective Radical Hydroacylation of Enals with α-Ketoacids Enabled by Photoredox/Amine Cocatalysis

Visible-Light-Induced Radical Acylation of Imines with α-Ketoacids Enabled by Electron-Donor-Acceptor Complexes.

An enantioselective and branch-regioselective α-allylation of N-methyl anilines under dual palladium/photoredox catalysis is described. Readily available N-methyl anilines are used as formal “hard”...

Hong-Hao Zhang

Papers

Enantioselective Allylic Alkylation with 4-Alkyl-1,4-dihydro-pyridines Enabled by Photoredox/Palladium Cocatalysis

A review of enantioselective dual transition metal/photoredox catalysis

Enantioselective Radical Hydroacylation of Enals with α-Ketoacids Enabled by Photoredox/Amine Cocatalysis

Visible-Light-Induced Radical Acylation of Imines with α-Ketoacids Enabled by Electron-Donor-Acceptor Complexes.

Enantioselective α-Allylation of Anilines Enabled by a Combined Palladium and Photoredox Catalytic System