Robin

In this work, we report a novel light-mediated desaturation strategy enabled by electron donor–acceptor complex formation. DFT and mechanistic studies reveal that the reaction proceeds via single-electron transfer, hydrogen atom transfer, and base-mediated deprotonation sequentially with pyridinium salt serving dually as oxidant and base, and hexafluoroisopropanol functioning as solvent and radical mediator. Notably, this strategy demonstrates broad substrate scope, enabling efficient synthesis of quinolinones, coumarins, and flavones, and also facilitates the late-stage functionalization of drug molecules.

Abstract

Recently, electron donor–acceptor (EDA) complex-mediated organic synthetic strategies have emerged as powerful tools for diverse bond-forming transformations; however, their efficiency often diminishes when ionic reactants are involved. This limitation arises from the requirement of polar solvents such as DMSO or DMF to solubilize ionic species for the formation of effective EDA complex. Consequently, these solvents engage in competing EDA complex formation or disrupt ionization equilibria. In parallel, there is a pressing necessity of modern and efficient strategy to achieve dehydrogenation reactions, which are in general limited by the drawbacks of traditional approaches. To address both, herein, we disclose an innovative desaturation strategy based on the formation of an EDA complex between a dihydrogenated organic substrate and an N-methoxy pyridinium salt. In our study, solubility issues, which are associated with the pyridinium salt, are effectively addressed by using hexafluoroisopropanol (HFIP). Beyond enhancing solubility, HFIP also functions as a transient H-shuttle, significantly reducing the activation energy for this transformation. This cooperative interplay between HFIP and the pyridinium salt enables the efficient and selective desaturation of a broad range of heterocyclic carbonyl compounds—including quinolinones, coumarins, and flavones—which are valuable scaffolds in pharmaceutical and agrochemical research. At the end, detailed mechanistic studies with the aid of experiments as well as DFT studies clearly disclose the mechanism as well as the important role of HFIP in this reaction.

Nature Catalysis, Published online: 13 February 2023; doi:10.1038/s41929-023-00914-7

Hydrofunctionalization of α-olefins with mineral acids usually proceeds with Markovnikov selectivity. Now, a strategy based on synergistic phase transfer and photoredox catalysis is developed to facilitate anti-Markovnikov addition of aqueous hydrochloric and nitric acid to unactivated alkenes.

[Bis(monofluoroacetoxy)iodo]benzene, an efficient and alternative reagent for radical monofluoromethylation under visible-light copper(I) photoredox catalysis, provides access to CH₂F-containing organic compounds. The broad utility of this radical monofluoromethylating reagent in alkene oxy-monofluoromethylation reactions, including for the synthesis of fluoromethylated amino acid derivatives and heterocycles, is demonstrated.

Abstract

A simple process for the oxy-monofluoromethylation of alkenes is described. In combination with visible-light copper(I) photoredox catalysis, an easily accessible iodine(III) reagent containing monofluoroacetoxy ligands serves as a powerful source of a monofluoromethyl (CH₂F) radical, enabling the step economical synthesis of γ-fluoro-acetates from a broad range of olefinic substrates under mild conditions. Applications to late-stage diversification of alkenes derived from complex molecules, amino acids and the synthesis of fluoromethylated heterocycles are also demonstrated.

A photocatalytic carboxylation of C−N bonds in cyclic amines with CO₂ is realized by consecutive photo-induced electron transfer (ConPET). This mild and transition-metal-free protocol provides a general and practical route to valuable β-, γ-, δ- and ϵ-amino acids.

Abstract

Visible-light photocatalytic carboxylation with CO₂ is highly important. However, it still remains challenging for reluctant substrates with low reduction potentials. Herein, we report a novel photocatalytic carboxylation of C−N bonds in cyclic amines with CO₂ via consecutive photo-induced electron transfer (ConPET). It is also the first photocatalytic reductive ring-opening reaction of azetidines, pyrrolidines and piperidines. This strategy is practical to transform a variety of easily available cyclic amines to valuable β-, γ-, δ- and ϵ-amino acids in moderate-to-excellent yields. Moreover, the method also features mild and transition-metal-free conditions, high selectivity, good functional-group tolerance, facile scalability and product derivations. Mechanistic studies indicate that the ConPET might be the key to generating highly reactive photocatalysts, which enable the reductive activation of cyclic amines to generate carbon radicals and carbanions as the key intermediates.

Publication date: 11 August 2022

Source: Chem, Volume 8, Issue 8

Author(s): Xin Li, Yang Shui, Pingkang Shen, Yi-Peng Wang, Chi Zhang, Chao Feng

Nature Synthesis, Published online: 30 May 2022; doi:10.1038/s44160-022-00074-9

Methods for the hydrofluoroalkylation of alkenes often require expensive reagents and have limited reaction scope. Now, a photoinduced manganese-catalysed hydrofluoroalkylation is reported, providing an array of fluoroalkyl-containing products from fluoroalkyl halides. Mechanistic studies reveal that the bidentate phosphine ligand plays a key role in atom transfer processes and increases the stability and lifetime of the metalloradical intermediate.

Formal β-C−H (hetero)arylation of aldehydes and ketones via their readily prepared silyl enol ethers has been achieved by dual nickel and photoredox catalysis. This reaction features broad scope and excellent functional group tolerance.

Abstract

α-C−H-functionalization of ketones and aldehydes has been intensively explored in organic synthesis. The functionalization of unactivated β-C−H bonds in such carbonyl compounds is less well investigated and developing a general method for their β-C−H arylation remains challenging. Herein we report a method that uses cooperative nickel and photoredox catalysis for the formal β-C−H arylation of aldehydes and ketones with (hetero)aryl bromides. The method features mild conditions, remarkable scope and wide functional group tolerance. Importantly, the introduced synthetic strategy also allows the β-alkenylation, β-alkynylation and β-acylation of aldehydes under similar conditions. Mechanistic studies revealed that this transformation proceeds through a single electron oxidation/Ni-mediated coupling/reductive elimination cascade.

Abstract

An photosensitizer- and additive-free, visible-light-induced decarboxylative aminoalkylation/C−O coupling cyclization of enaminones with N-arylglycine for the synthesis of 3-aminoalkyl chromones has been achieved. This synthetic method features good functional-group tolerance, mild reaction conditions and no request of photocatalyst or additive, thus making this protocol more practical and sustainable.

Abstract

A visible-light-mediated intermolecular radical insertion of isocyanides to electron-deficient o-alkenylanilines leading to isoindolinone is reported. Deuterium (D₂O) and H₂O¹⁸ labelling experiments suggest H and O incorporation in the product. The formation of an N-centered radical (NCR) via stepwise PT/ET process was confirmed by radical trapping experiments, photoluminescence, cyclic voltammetry and DFT studies. This photo cascade methodology is overall a redox neutral process featuring metal-free condition and broad substrate scope (32 examples). The synthesis of analogue of GABA receptor antagonist shows the practical utility of this method.

A visible-light-driven base-enabled free radical reaction of 1,6-enynes and ICF₂COOEt was developed via cascade difluoroalkylation/5-exo-dig cyclization/iodination without catalyst and oxidants. The reaction provided difluoroalkylated and vinyl C−I bonds containing pyrrolidines and tetrahydrofuran derivatives in good yields and excellent Z/E stereoselectivity.

Abstract

A visible-light-driven base-promoted radical cascade difluoroalkylation/5-exo-dig cyclization/iodination of 1,6-enynes with ethyl difluoroiodoacetate was developed under catalyst-free and oxidant-free conditions. The difluoroalkylated pyrrolidines and tetrahydrofuran derivatives were generated with good functional group tolerance and high Z/E stereoselectivity. This reaction provided an alternative and mild method for the preparation of highly functionalized and vinyl C−I bonds containing five-membered heterocyclic products.

A highly enantioselective hydroaminoalkylation of alkenyl azaarenes is described as the first successful catalytic asymmetric conjugate addition of radicals to activated olefins to directly forge stereocenters at their β-position. The stereoselective transformation was made possible by the introduction of cooperative nonclassical H-bonding interactions, thus enabling the chiral catalyst to provide sufficient stereocontrol.

Abstract

Chiral hydrogen-bonding (H-bonding) catalytic asymmetric conjugate addition to activated olefins has been widely used to access enantioenriched molecules containing stereocenters at the β-position of the olefin activating groups. Herein, we report the first highly enantioselective radical-based manifold. Under a dual organocatalyst system involving a chiral phosphoric acid and DPZ as the photoredox sensitizer, transformations of N-arylglycines, in which aryls with CF₃ substituents are introduced, with alkenyl azaarenes afforded valuable hydroaminoalkylation adducts with satisfactory results. In addition to the diversity of azaarenes, the method can be used to construct aryl-, alkyl- and silyl-substituted stereocenter. Control experiments and density functional theory calculations were performed to elucidate a plausible reaction mechanism and the origin of stereoselectivity, wherein nonclassical H-bonding interactions were found to assist chiral catalysts in offering sufficient enantiocontrol.

Polyethylene terephthalate (PET) and CO₂, two chemical wastes that urgently need to be transformed in our environment, are converted simultaneously in a one-pot catalytic process. The process for dual-promoted conversion overcomes the original thermodynamic equilibrium limits of methanol synthesis and PET methanolysis, leading to a significantly enhanced yield of PET.

Abstract

Polyethylene terephthalate (PET) and CO₂, two chemical wastes that urgently need to be transformed in the environment, are converted simultaneously in a one-pot catalytic process through the synergistic coupling of three reactions: CO₂ hydrogenation, PET methanolysis and dimethyl terephthalate (DMT) hydrogenation. More interestingly, the chemical equilibria of both reactions were shifted forward due to a revealed dual-promotion effect, leading to significantly enhanced PET depolymerization. The overall methanol yield from CO₂ hydrogenation exceeded the original thermodynamic equilibrium limit since the methanol was in situ consumed in the PET methanolysis. The degradation of PET by a stoichiometric ratio of methanol was significantly enhanced because the primary product, DMT was hydrogenated to dimethyl cyclohexanedicarboxylate (DMCD) or p-xylene (PX). This synergistic catalytic process provides an effective way to simultaneously recycle two wastes, polyesters and CO₂, for producing high-value chemicals.