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

Visible-light photoredox catalysis offers a distinct activation mode complementary to thermal transition metal catalyzed reactions. The vast majority of photoredox processes capitalizes on precious metal ruthenium(II) or iridium(III) complexes that serve as single-electron reductants or oxidants in their photoexcited states. As a low-cost alternative, organic dyes are also frequently used but in general suffer from lower photostability. Copper-based photocatalysts are rapidly emerging, offering not only economic and ecological advantages but also otherwise inaccessible inner-sphere mechanisms, which have been successfully applied to challenging transformations. Moreover, the combination of conventional photocatalysts with copper(I) or copper(II) salts has emerged as an efficient dual catalytic system for cross-coupling reactions.

Copper's rapid ascent in visible-light photoredox catalysis.

The first highly enantioselective catalytic protocol for the reductive coupling of ketones and hydrazones is reported. These reactions proceed through neutral ketyl radical intermediates generated via a concerted proton-coupled electron transfer (PCET) event jointly mediated by a chiral phosphoric acid catalyst and the photoredox catalyst Ir(ppy)2(dtbpy)PF6. Remarkably, these neutral ketyl radicals appear to remain H-bonded to the chiral conjugate base of the Brønsted acid during the course of a subsequent C-C bond-forming step, furnishing syn 1,2-amino alcohol derivatives with excellent levels of diastereo- and enantioselectivity. This work provides the first demonstration of the feasibility and potential benefits of concerted PCET activation in asymmetric catalysis.

Enantioselective photoredox catalysis enabled by proton-coupled electron transfer

In recent years, visible light-induced transition metal catalysis has emerged as a new paradigm in organic photocatalysis, which has led to the discovery of unprecedented transformations as well as the improvement of known reactions. In this subfield of photocatalysis, a transition metal complex serves a double duty by harvesting photon energy and then enabling bond forming/breaking events mostly via a single catalytic cycle, thus contrasting the established dual photocatalysis in which an exogenous photosensitizer is employed. In addition, this approach often synergistically combines catalyst-substrate interaction with photoinduced process, a feature that is uncommon in conventional photoredox chemistry. This Review describes the early development and recent advances of this emerging field.

Visible Light-Induced Transition Metal Catalysis.

ConspectusCross-coupling reactions have been established as potential tools for manufacture of complex molecular frameworks of diversified interests by connecting two simple molecules through the formation of a carbon–carbon (C–C) or a carbon–heteroatom (C–X) bond. Conventional cross-couplings are transition metal-catalyzed reactions between electrophiles and nucleophiles. Generally, the electrophilic partner is an aryl or alkenyl halide, the nucleophile is an organometallic reagent, and both are obtained from prefunctionalization of their corresponding hydrocarbons. During the past decade, transition metal-catalyzed dehydrogenative cross-couplings between two carbon–hydrogen (C–H) bonds and between one C–H bond and one heteroatom–hydrogen (X–H) bond, which build a C–C and a C–X linkage respectively, have emerged as an attractive strategy in synthetic chemistry. Such straightforward couplings allow use of less functionalized reagents, thus reducing the number of steps to the target molecule and minimizing...

Photocatalytic Activation of Less Reactive Bonds and Their Functionalization via Hydrogen-Evolution Cross-Couplings.

Transition-metal-catalyzed C-N bond-forming reactions have emerged as fundamental and powerful tools to construct arylamines, a common structure found in drug agents, natural products, and fine chemicals. Reported herein is an alternative access to heteroarylamine via radical-radical cross-coupling pathway, powered by visible light catalysis without any aid of external oxidant and reductant. Only by visible light irradiation of a photocatalyst, such as a metal-free photocatalyst, does the cascade single-electron transfer event for amines and heteroaryl nitriles occur, demonstrated by steady-state and transient spectroscopic studies, resulting in an amine radical cation and aryl radical anion in situ for C-N bond formation. The metal-free and redox economic nature, high efficiency, and site-selectivity of C-N cross-coupling of a range of available amines, hydroxylamines, and hydrazines with heteroaryl nitriles make this protocol promising in both academic and industrial settings.

Metal-Free, Redox-Neutral, Site-Selective Access to Heteroarylamine via Direct Radical-Radical Cross-Coupling Powered by Visible Light Photocatalysis.

Copper compounds involved in photocatalysis have recently spurred considerable interest for their novel transformations. However, mechanistic investigations are still in infancy. We find a new type of reaction, that is, Cu(II) salt-catalyzed C-H functionalization of aromatic amines triggered by visible light irradiation. An array of mechanistic observations, including high-resolution mass spectrometry, ultraviolet-visible absorption spectrum, electron spin resonance, x-ray absorption near-edge structure, and density functional theory calculation, have identified the key intermediates generated in situ in the transformation. Integration of single-electron transfer, singlet oxygen (1O2), and new absorption species, intermediate I and intermediate II formed in situ from Cu(II) salts and substrate amines or imines, respectively, is responsible for the N-H and C-H bond activation of secondary amines to couple with nucleophiles in air, thereby leading to the formation of quinoline, indolo[3,2-c]quinoline, β-amino acid, and 1,4-dihydropyridine derivatives in moderate to good yields under visible light irradiation at room temperature.

https://advances.sciencemag.org/content/advances/3/8/e1700666.full.pdf

Identifying key intermediates generated in situ from Cu(II) salt-catalyzed C-H functionalization of aromatic amines under illumination.

As one of the most ubiquitous bulk reagents available, the intrinsic chemical inertness of tetrahydrofuran (THF) makes direct and site-selective C(sp 3 )-H bond activation difficult, especially under redox neutral condition. Here, we demonstrate that semiconductor quantum dots (QDs) can activate α-C-H bond of THF via forming QDs/THF conjugates. Under visible light irradiation, the resultant alkoxyalkyl radical directly engages in radical cross-coupling with α-amino radical from amino C-H bonds or radical addition with alkene or phenylacetylene, respectively. In contrast to stoichiometric oxidant or hydrogen atom transfer reagents required in previous studies, the scalable benchtop approach can execute α-C-H bond functionalization of THF only by a QD photocatalyst under redox-neutral condition, thus providing a broad of value added chemicals starting from bulk THFs reagent. The high step- and atom-economy, high efficiency and broad substrate scope make the photocatalysis with QDs and visible light promising in both academic and industrial setting.

Direct, Site-Selective and Redox-Neutral α-C−H Bond Functionalization of Tetrahydrofurans via Quantum Dots Photocatalysis

Photoredox Oxo-C(sp3)-H Bond Functionalization via in Situ Cu(I)-Acetylide Catalysis.

Photo[2+2]cycloaddition of olefins is a sought-after tool for making cyclobutanes, which are the building blocks for a wide range of biologically active molecules and natural products. However, the...

https://www.chinesechemsoc.org/doi/pdf/10.31635/ccschem.019.201900049

Zan Liu

Papers

Metal-Free, Redox-Neutral, Site-Selective Access to Heteroarylamine via Direct Radical-Radical Cross-Coupling Powered by Visible Light Photocatalysis.

Identifying key intermediates generated in situ from Cu(II) salt-catalyzed C-H functionalization of aromatic amines under illumination.

Direct, Site-Selective and Redox-Neutral α-C−H Bond Functionalization of Tetrahydrofurans via Quantum Dots Photocatalysis

Photoredox Oxo-C(sp3)-H Bond Functionalization via in Situ Cu(I)-Acetylide Catalysis.

Aggregation-Enabled Intermolecular Photo[2+2]cycloaddition of Aryl Terminal Olefins by Visible-Light Catalysis