General photoactivation of electron donor–acceptor (EDA) complexes between arylsulfonium salts and 1,4-diazabicyclo[2.2.2]octane with visible light or natural sunlight was discovered. This practical and efficient mode enables the production of aryl radicals under mild conditions, providing an unrealized opportunity for two-step para-selective C–H functionalization of complex arenes. The novel mode for generating aryl radicals via an EDA complex was well supported by UV-vis absorbance measurements, nuclear magnetic resonance titration experiments, and density functional theory (DFT) calculations. The method was applied to the regio- and stereo-selective arylation of various N-heterocycles under mild conditions, yielding an assembly of challengingly linked heteroaryl–(hetero)aryl products. Remarkably, the meaningful couplings of bioactive molecules with structurally complex drugs or agricultural pharmaceuticals were achieved to display favorable in vitro antitumor activities, which will be of great value in academia or industry.

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A general electron donor–acceptor complex for photoactivation of arenes via thianthrenation

https://arts.units.it/bitstream/11368/3018791/1/Org.%20Lett.%202022_HAS%20fenoli.pdf

The Photochemical Activity of a Halogen-Bonded Complex Enables the Microfluidic Light-Driven Alkylation of Phenols

We developed organocatalyst systems to promote the cleavage of stable C-H bonds, such as formyl, α-hydroxy, and benzylic C-H bonds, through a hydrogen atom transfer (HAT) process without the use of exogenous photosensitizers. An electronically tuned thiophosphoric acid, 7,7'-OMe-TPA, was assembled with substrate or co-catalyst N-heteroaromatics through hydrogen bonding and π-π interactions to form electron donor-acceptor (EDA) complexes. Photoirradiation of the EDA complex induced stepwise, sequential single-electron transfer (SET) processes to generate a HAT-active thiyl radical. The first SET was from the electron-rich naphthyl group of 7,7'-OMe-TPA to the protonated N-heteroaromatics and the second proton-coupled SET (PCET) from the thiophosphoric acid moiety of 7,7'-OMe-TPA to the resulting naphthyl radical cation. Spectroscopic studies and theoretical calculations characterized the stepwise SET process mediated by short-lived intermediates. This organocatalytic HAT system was applied to four different carbon-hydrogen (C-H) functionalization reactions, hydroxyalkylation and alkylation of N-heteroaromatics, acceptorless dehydrogenation of alcohols, and benzylation of imines, with high functional group tolerance.

Identification of a Self-Photosensitizing Hydrogen Atom Transfer Organocatalyst System.

Synthesis of β-hydroxysulfides via visible-light-driven and EDA complex-promoted hydroxysulfenylation of styrenes with heterocyclic thiols in EtOH under photocatalyst-free conditions

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C-H functionalization approaches that make use of low energy photons as a controllable energy source. Compared to traditional late-stage functionalization strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- and chemoselectivities. Merging the compelling benefits of photocatalysis with the late-stage functionalization workflow offers a potentially unmatched arsenal to tackle drug development campaigns and beyond. This Review highlights the photocatalytic late-stage C-H functionalization strategies of small-molecule drugs, agrochemicals, and natural products, classified according to the targeted C-H bond and the newly formed one. Emphasis is devoted to identifying, describing, and comparing the main mechanistic scenarios. The Review draws a critical comparison between established ionic chemistry and photocatalyzed radical-based manifolds. The Review aims to establish the current state-of-the-art and illustrate the key unsolved challenges to be addressed in the future. The authors aim to introduce the general readership to the main approaches toward photocatalytic late-stage C-H functionalization, and specialist practitioners to the critical evaluation of the current methodologies, potential for improvement, and future uncharted directions.

Photocatalytic Late-Stage C-H Functionalization.

Thiophenol was discovered to form an EDA complex with iodobenzene through halogen bonding interactions upon treatment with KOH. A direct photochemical thiolation of C(sp3)–H bond-containing etheric, allylic, and benzylic substrates with thiophenol was developed. The reaction proceeded on the basis of the in situ generation of a thiyl radical and aryl radical through single electron transfer between the photoexcited thiophenolate anion and aryl iodide EDA complex. Then a C(sp3) centred-radical was formed by aryl radical-mediated hydrogen atom transfer and the thiolation products were delivered via a radical–radical cross-coupling with the thiyl radical.

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Correction: A photoexcited halogen-bonded EDA complex of the thiophenolate anion with iodobenzene for C(sp3)–H activation and thiolation

A formylation of aryl iodides at room temperature using a weaker base KOMe instead of BuLi was developed. The TMS-TMS disilane was discovered to play crucial roles in this formylation. It was found that the MeO− group of KOMe coordinated with two silyl groups of disilane to generate a hypercoordinate silane species. This hypercoordinate silane species reacted with aryl iodide to give an aryl carbanion, which underwent formylation with DMF to give an aryl aldehyde.

Jiaying Tang

Papers

Correction: A photoexcited halogen-bonded EDA complex of the thiophenolate anion with iodobenzene for C(sp3)–H activation and thiolation

Potassium methoxide/disilane-mediated formylation of aryl iodides with DMF at room temperature