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Alkyl and acyl radicals play a critical role in the advancement of chemical synthesis. The generation of acyl and alkyl radicals by activation of C–O bonds using visible-light photoredox catalysis offers a mild and environmentally benign approach to useful chemical transformations. Alcohols, carboxylic acids, anhydrides, xanthates, oxalates, N-phthalimides, and thiocarbonates are some examples of alkyl and acyl precursors that can produce reactive radicals by homolysis of the C–O bond. These radicals can then go through a variety of transformations that are beneficial for the construction of synthetic materials that are otherwise difficult to access. This study summarizes current developments in the use of organic photocatalysts, transition-metal photoredox catalysts, and metallaphotocatalysts to produce acyl and alkyl radicals driven by visible light.

The formyl C−H thiolation of aldehydes using thiosulfonates and the decatungstate anion as a photocatalyst is reported. Using this photocatalytic protocol together with a CO atmosphere, both aromatic and aliphatic thioesters can be synthesized in good yields. The transformation consists of a cascade of double SH2 reactions, HAT and an ArS group transfer. CO atmosphere effectively limits the extent of decarbonylation of acyl radicals that are generated in the reaction. [ABSTRACT FROM AUTHOR]

In these transformations, the stable and easily available -keto acids were employed as the acyl radical precursors, while iodide and nickel catalysis facilitate the acyl radical generation. Mechanistically, the Minisci-type acylation includes three key processes: acyl radical generation, radical addition of acyl radicals to N-heterocycles, and formal hydrogen atom loss. Keywords: electrosynthesis; Minisci reaction; acyl radical; -keto acids; anodic oxidation EN electrosynthesis Minisci reaction acyl radical -keto acids anodic oxidation 3026 3032 7 08/31/23 20230915 NES 230915 Graph The Minisci-type reaction constitutes a robust tactic to construct functionalized N-heterocycles via radical pathways in a single step. Electrosynthesis, Minisci reaction, -keto acids, acyl radical, anodic oxidation. [Extracted from the article]

A new way to form fluorenones via the direct excitation of substrates instead of photocatalyst to activate the C(sp2)−H bond under redox‐neutral condition is reported. Our design relies on the photoexcited aromatic aldehyde intermediates that can be intercepted by cobaloxime catalyst through single electron transfer for following β‐H elimination. The generation of acyl radical and successful interception by a metal catalyst cobaloxime avoid the use of a photocatalyst and stoichiometric external oxidants, affording a series of highly substituted fluorenones, including six‐membered ketones, such as xanthone and thioxanthone derivatives in good to excellent yields, and with hydrogen as the only byproduct. This catalytic system features a readily available metal catalyst, mild reaction conditions and broad substrate scope, in which sunlight reaction and scale‐up experiments by continuous‐flow approach make the new methodology sustainable and amenable for potentially operational procedures. [ABSTRACT FROM AUTHOR]

In this review, we highlighted the main achievements in the field of electrocatalytic generation of acyl radicals and their applications. These electrochemical strategies were introduced with an emphasis on the substrate scope, reaction limitation and underlying mechanism. The related reactions were categorized according to the pathways of acyl radical generation, including outer‐sphere electron transfer (ET), inner‐sphere ET, and hydrogen atom transfer (HAT) processes. [ABSTRACT FROM AUTHOR]

A metal- and aldehyde-free visible-light-driven photoredox-neutral alkene acylarylation with readily available cyanoarenes is described. A variety of 3-(arylmethyl)chroman-4-ones (i.e., homoisoflavonoids) and analogs are efficiently synthesized with good functional group tolerance. This mild protocol relies on a phosphoranyl radical-mediated acyl radical-initiated cyclization and selective radical-radical coupling sequence, and is also further highlighted by subsequent derivatization to chromone and 2H-chromene as well as its application in the three-component alkene acylarylation.

An intramolecular hydroacylation of olefins using carboxylic acids (CAs) has been developed. With the aid of a boronic acid, CAs can be used as acyl‐radical precursors in catalytic photoredox reactions driven by visible light. The CAs are easily converted into their corresponding cyclic ketones without the need to use any stoichiometric activating reagents. Mechanistic studies implied that the formation of an "ate" complex from the CA and boronic acid is crucial for the generation of the acyl radical equivalent from the unreactive carboxy group. [ABSTRACT FROM AUTHOR]

Alkyl and acyl radicals play a critical role in the advancement of chemical synthesis. The generation of acyl and alkyl radicals by activation of C - O bonds using visible-light photoredox catalysis offers a mild and environmentally benign approach to useful chemical transformations. Alcohols, carboxylic acids, anhydrides, xanthates, oxalates, N -phthalimides, and thiocarbonates are some examples of alkyl and acyl precursors that can produce reactive radicals by homolysis of the C - O bond. These radicals can then go through a variety of transformations that are beneficial for the construction of synthetic materials that are otherwise difficult to access. This study summarizes current developments in the use of organic photocatalysts, transition-metal photoredox catalysts, and metallaphotocatalysts to produce acyl and alkyl radicals driven by visible light., (Copyright © 2024, Roy et al.)

The alkynylbenziodoxole derivatives are recently developed alkynylation reagents in organic synthesis, which demonstrate excellent radical alkynylation reactivity in photoredox catalysis reactions. Herein we report the synthesis of alkynylbenziodoxole derivatives with difluoro, monofluoro, monomethoxy, and dimethoxy substitution on the benziodoxole moiety, and investigated their radical alkynylation reactivity for the first time. A series of mechanistic experiments were conducted to study the radical acceptor and oxidative quencher reactivity of alkynylbenziodoxoles, in which unsubstituted alkynylbenziodoxoles played balancing roles in both processes, while electron-rich benziodoxole derivatives demonstrate synthetic advantages in some cases.

Nitro(hetero)arene derivatives are essential commodity chemicals used in various products, such as drugs, polymers, and agrochemicals. In this study, we leverage the excited-state reactivities of copper catalysts and nitro(hetero)arenes, and the Umpolung reactivity of acyl radicals to convert readily available nitro(hetero)arenes directly to valuable 2-aminophenol derivatives, which are important scaffolds in many top-selling pharmaceuticals. This reaction is applicable to a variety of nitro(hetero)arenes, acyl chlorides, and late-stage modifications of complex molecules, making it a useful tool for the discovery of new functional molecules. Mechanistic studies, including radical trapping experiments, Stern Volmer quenching studies, light ON/OFF experiments, and 18 O-labeling studies, suggest a reaction mechanism involving photoexcitation of a copper complex, diradical couplings, and an in-cage contact ion pair (CIP) migration. Our findings offer a streamlined protocol for synthesizing essential pharmacophores from nitro(hetero)arenes while simultaneously advancing knowledge in excited-state and radical chemistry and stimulating new reaction design and development., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

A visible‐light‐induced cascade radical cyclization of aroyl chlorides with 2‐(allyloxy)‐benzaldehyde derivatives has been developed. The method takes advantages of unactivated C=C bonds as the acyl radical acceptors and offers a mild and green approach for the synthesis of 1,4‐diketones bearing biologically important chroman‐4‐one skeletons with moderate to good yields. [ABSTRACT FROM AUTHOR]

Visible light photocatalytic radical carbonylation has been established as a robust tool for the efficient synthesis of carbonyl-containing compounds. Acyl radicals serve as the key intermediates in these useful transformations and can be generated from the addition of alkyl or aryl radicals to carbon monoxide (CO) or various acyl radical precursors such as aldehydes, carboxylic acids, anhydrides, acyl chlorides or α-keto acids. In this review, we aim to summarize the impact of visible light-induced acyl radical carbonylation reactions on the synthesis of oxygen and nitrogen heterocycles. The discussion is mainly categorized based on different types of acyl radical precursors.

Abstract: A photoredox‐mediated acylation reaction of electron deficient heteroarenes with terminal alkynes is reported. The method relies on oxidative cleavage of phenylacetylenes for generation of acyl radicals as a key enabling feature. The reaction is regioselective with broad substrate scope. Quantum yield investigations support a radical chain mechanism. [ABSTRACT FROM AUTHOR]

A highly efficient and straightforward approach for the synthesis of spiroepoxy chroman-4-one derivatives was developed using a visible light-enabled tandem radical strategy. The reaction is initiated by the formation of an acyl radical that undergoes intramolecular radical cyclization and epoxidation. The optimal result was obtained with 1 mol% of Ru(bpy)3Cl2⋅6H2O, TBHP, and K2CO3 in i-PrOAc at room temperature with irradiation from a blue LED. This unprecedented tandem approach utilizes a broad range of substrates, and provides a convenient and powerful synthetic tool for accessing the synthetically useful spiroepoxy chroman-4-ones and their nitrogen-containing derivatives. [ABSTRACT FROM AUTHOR]

The dehydrodimerization of 2-butanone or 3-pentanone by lead dioxide leads to 3,4-dimethyl-2,5-hexanedione or 4,5-dimethyl-3,6-octanedione in nearly quantitative yield. This very clean and efficient reaction has been studied from mechanistic and stereochemical points of view. Dehydrodimerization of a 1:1 molar mixture of 2-butanone and 3-pentanone leads to 3,4-dimethyl-2,4-heptanedione in ∼50% yield. From these γ -diketones, 2,3,4-trimethylcyclopentenone, 3,4,5-trimethylcyclopentenone, 2,3,4,5-tetramethylcyclopentenone or 3-ethyl-2,4,5-trimethylcyclopentenone were obtained. [ABSTRACT FROM AUTHOR]

A new way to form fluorenones via the direct excitation of substrates instead of photocatalyst to activate the C(sp 2 )-H bond under redox-neutral condition is reported. Our design relies on the photoexcited aromatic aldehyde intermediates that can be intercepted by cobaloxime catalyst through single electron transfer for following β-H elimination. The generation of acyl radical and successful interception by a metal catalyst cobaloxime avoid the use of a photocatalyst and stoichiometric external oxidants, affording a series of highly substituted fluorenones, including six-membered ketones, such as xanthone and thioxanthone derivatives in good to excellent yields, and with hydrogen as the only byproduct. This catalytic system features a readily available metal catalyst, mild reaction conditions and broad substrate scope, in which sunlight reaction and scale-up experiments by continuous-flow approach make the new methodology sustainable and amenable for potentially operational procedures., (© 2022 Wiley-VCH GmbH.)

A metal- and aldehyde-free visible-light-driven photoredox-neutral alkene acylarylation with readily available cyanoarenes is described. A variety of 3-(arylmethyl)chroman-4-ones (i.e., homoisoflavonoids) and analogs are efficiently synthesized with good functional group tolerance. This mild protocol relies on a phosphoranyl radical-mediated acyl radical-initiated cyclization and selective radical-radical coupling sequence, and is also further highlighted by subsequent derivatization to chromone and 2 H -chromene as well as its application in the three-component alkene acylarylation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Yu, Ren, Lu, Fu, Zhang, Wang, Bai, Hao, Yang, Wei, Yi and Wei.)

Abstract: 2-Formylphenoxy quinones can be converted into xanthones via an acyl radical intermediate with NBS and AIBN. [Copyright &y& Elsevier]

Abstract: The addition of the acetyl radical to benzene, aniline, trifluoromethylbenzene and naphthalene has been investigated using DFT calculations. Addition to benzene is calculated to have an energy barrier of 63.6kJmol−1 at the BHandHLYP/6-311G(d,p)+ZPE level of theory. This reaction is associated with simultaneous SOMO→π∗ and π→SOMO interactions with the latter interaction dominating, suggesting that acetyl reacts predominantly as an electrophilic radical in its interaction with benzene. Addition to the ortho and para positions of aniline is calculated to be slightly less favourable, while attack at the meta position is predicted to be unaffected in relation to the chemistry involving benzene. Inclusion of the electron-withdrawing substituent, trifluoromethyl, is predicted to accelerate reactions slightly at the ortho and para positions, while attack at the C1 position of naphthalene is calculated to involve a barrier of 50.3kJmol−1 (BHandHLYP/6-311G(d,p)+ZPE). [ABSTRACT FROM AUTHOR]

In order to synthesize new tricyclic β-lactams we have studied the reactivity of 4-alkenylepoxy-N-(1-cyano-1-dimethylethyl)-2-azetidinones with Cp2TiCl. The desired trilactams were not formed at all but an unsaturated nitrile and an aldehyde were obtained instead. Under similar reaction conditions, the treatment of styrylnitrile with Cp2TiCl afforded the styrylaldehyde. The formation of aldehydes in these reactions suggest the generation of acyl radicals from nitriles mediated by Cp2TiCl. [ABSTRACT FROM AUTHOR]

The addition of the acetyl radical at the various positions in both pyridine and the pyridinium ion has been investigated using DFT calculations. Additions at the 2-, 3- and 4-positions in these systems are associated with simultaneous SOMO→π* and π→SOMO interactions, with the former interaction dominating in the case of pyridine, and that latter in the case of pyridinium. Simultaneous SOMO→π*, LPN→SOMO and LPN→π*c=o interactions are predicted for the addition at the nitrogen atom in pyridine. The energy barrier for attack at the nitrogen atom in pyridine is calculated to be 54 kJ mol−1 at the BHandHLYP/6-311G(d,p) level of theory, some 6 kJ mol−1 lower than for the analogous attack at any other atom in pyridine, or at any position in the pyridinium ion. Multiorbital interactions are responsible this preference, resulting in an unusual motion vector in the transition state for attack at the nitrogen atom in pyridine. [Copyright &y& Elsevier]

Abstract: The product of the reaction of muonium with tert-butylisocyanate was previously assigned as the muoniated tert-butylaminyl radical (I. McKenzie, J.-C. Brodovitch, K. Ghandi, S. Kecman, P. W. Percival, Physica B 326 (2003) 76). This assignment is incorrect since the muon and 14N hyperfine-coupling constants (hfcc) of this radical would have the opposite sign, which is in conflict with the experimental results. The radical is now reassigned as the muoniated N-tert-butylcarbamoyl radical, based on the similarities between the experimental muon and 14N hfcc and hfcc calculated at the UB3LYP/6-311G(d,p)//UB3LYP/EPR-III level. The large zero-point energy in the N–Mu bond results in the dissociation barrier of the muoniated N-tert-butylcarbamoyl radical being above the combined energy of the reactants, in contrast to the N-tert-butylcarbamoyl radical where the dissociation barrier lies below the combined energy of the reactants. The reaction of muonium with tert-butylisothiocyanate produced both conformers of the muoniated N-tert-butylthiocarbamoyl radical and their assignment was based on the similarities between the experimental and calculated muon hfcc. These are the first acyl and thioacyl radicals to be directly detected by muon spin spectroscopy. [Copyright &y& Elsevier]

Glyoxal is a key compound involved in glyoxal oxidase (GLOX)-dependent production of glyoxylate, oxalate and H2O2 by lignin-degrading basidiomycetes. In this paper, we report that glyoxal was produced from a metabolite of ligninolytic fungi, linoleic acid, by manganese peroxidase (MnP)-dependent lipid peroxidation. In the absence of the parent substrate of linoleic acid, the dialdehyde was oxidized by MnP and Mn(III) chelate to start free radical reactions with emission of chemiluminescence at 700–710 nm. The spectroscopic profile of the light emission is distinguishable from (a) singlet oxygen, (b) triplet carbonyls from dioxetane and α-hydroxyperoxyl radicals, and (c) biacyl triplet formed by the coupling of two acyl radicals. The photon emission of glyoxal by MnP was activated by co-oxidation of tartrate. The MnP-dependent oxidation of glyoxal in tartrate buffers continued for 10 days without addition of exogenous H2O2. The importance of these results is discussed in relation to the free radical chemistry of lignin biodegradation by wood rot fungi. [ABSTRACT FROM AUTHOR]

Lipid peroxidation by managanese peroxidase (MnP) is reported to decompose recalcitrant polycyclic aromatic hydrocabon (PAH) and nonphenolic lignin models. To elucidate the oxidative process, linoleic acid and 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid [13(S)-HPODE] were reacted with MnPs from Ceriporiopsis subvermispora and Bjerkandera adusta and the free radicals produced were analyzed by ESR. When the MnPs were reacted with 13(S)-HPODE in the presence of Mn(II), H2O2 and tert-nitrosobutane (t-NB), the ESR spectrum contained a sharp triplet of acyl radical (aN = 0.81 mT). Formation of acyl radical was also observed in the reactions of Mn(III)-tartrate with 13(S)-HPODE and with linoleic acid, but the latter reaction occurred explosively after an induction period of around 30 min. Reactions of MnP with linoleic acid in the presence of Mn(II), H2O2 and t-NB gave no spin adducts while addition of t-NB after preincubation of linoleic acid with MnP/Mn(II)/H2O2 for 2 h gave spin adducts of carbon-centered (aN = 1.53 mT, aH = 0.21 mT) and acyl (aN = 0.81 mT) radicals. In contrast to linoleic acid, methyl linoleate and oleic acid were not peroxidized by MnP and chelated Mn(III) within a few hours, indicating that structures containing both the 1,4-pentadienyl moiety and a free carboxyl group are necessary for inducing the peroxidation in a short reaction time. These results indicate that MnP-dependent lipid peroxidation is not initiated by direct abstraction of hydrogen from the bis-allylic position during turnover but proceeds by a Mn(III)-dependent hydrogen abstraction from enols and subsequent propagation reactions involving the formation of acyl radical from lipid hydroperoxide. This finding expands the role of chelated Mn(III) from a phenol oxidant to a strong generator of free radicals from lipids and lipid hydroperoxides in lignin biodegradation. [ABSTRACT FROM AUTHOR]

[Display omitted] Acylation of Baylis-Hillman carbonates by visible light catalysis has been reported. Acyl radical is produced by decarboxylation of α-keto acid. This method has mild conditions, wide substrate scope, good functional group tolerance, and moderate to good yield, which provides a new route for the acylation of Baylis-Hillman derivatives. [ABSTRACT FROM AUTHOR]

Abstract: Oxygen activation using an aldehyde as a sacrificial reductant and mediated by metalloporphyrins is a radical process with a variable induction period in which the macrocycle function is to generate the acyl radicals to initiate a chain mechanism. This function can be also efficiently promoted by simple metal salts, which leads to a very simple and practical oxidative system that is able to epoxidize alkenes in good yields. [Copyright &y& Elsevier]

In this account, we describe our recent developments on the four‐types of hypervalent iodine(III)‐mediated radical reactions in organic synthesis. Firstly, the activation of aldehydic C−H bonds can be successfully effected with hypervalent iodine(III) reagents, thereby allowing the synthesis of various ketones with high efficiency. Secondly, the site‐selective oxidation of unactivated C(sp3)−H bonds of hydrocarbon substrates was realized with designer hypervalent iodine(III) reagents. Thirdly, various perfluoroalkyl and α‐aminoalkyl radicals can be generated from sodium perfluoroalkanesulfinates and sodium α‐aminoalkanesulfinates, respectively, under the influence of hypervalent iodine(III) reagents. Finally, the efficient generation of difluoromethyl radical from hypervalent difluoroacetoxyliodine(III) reagent was realized by photolysis. These four different strategies are illustrated by using various selective radical approaches. [ABSTRACT FROM AUTHOR]

Visible light photocatalytic radical carbonylation has been established as a robust tool for the efficient synthesis of carbonyl-containing compounds. Acyl radicals serve as the key intermediates in these useful transformations and can be generated from the addition of alkyl or aryl radicals to carbon monoxide (CO) or various acyl radical precursors such as aldehydes, carboxylic acids, anhydrides, acyl chlorides or α-keto acids. In this review, we aim to summarize the impact of visible light-induced acyl radical carbonylation reactions on the synthesis of oxygen and nitrogen heterocycles. The discussion is mainly categorized based on different types of acyl radical precursors. [ABSTRACT FROM AUTHOR]

Visible light photoredox catalysis has enabled easy access to acyl radicals under mild reaction conditions. Reactive acyl radicals, generated from various acyl precursors such as aldehydes, α-ketoacids, carboxylic acids, anhydrides, acyl thioesters, acyl chlorides, or acyl silanes, can undergo a diverse range of synthetically useful transformations, which were previously difficult or inaccessible. This review summarizes such recent progress of visible-light-driven acyl radical generation using transition metal photoredox catalysts, metallaphotocatalysts, hypervalent iodine catalysts or organic photocatalysts.

The inside cover picture, provided by Sungwoo Hong and co ‐ workers, illustrates a highly efficient and straightforward approach for the synthesis of spiroepoxy chroman ‐ 4 ‐ one derivatives with light irradiation using a blue LED under mild reaction conditions. During the reaction, the aldehyde generated in situ from the benzyl alcohol could further undergo visible light ‐ mediated internal radical cyclization and epoxidation, allowing the rapid generation of valuable and synthetically useful spiroepoxy chroman ‐ 4 ‐ ones and their nitrogen ‐ containing derivatives. Details of this work can be found in the communication on pages 3945 – 3949 (S. Jung, J. Kim, S. Hong, Adv. Synth. Catal. 2017, 359, 3945 – 3949; DOI: 10.1002/adsc.201701072). [ABSTRACT FROM AUTHOR]

The alkynylbenziodoxole derivatives are recently developed alkynylation reagents in organic synthesis, which demonstrate excellent radical alkynylation reactivity in photoredox catalysis reactions. Herein we report the synthesis of alkynylbenziodoxole derivatives with difluoro, monofluoro, monomethoxy, and dimethoxy substitution on the benziodoxole moiety, and investigated their radical alkynylation reactivity for the first time. A series of mechanistic experiments were conducted to study the radical acceptor and oxidative quencher reactivity of alkynylbenziodoxoles, in which unsubstituted alkynylbenziodoxoles played balancing roles in both processes, while electron-rich benziodoxole derivatives demonstrate synthetic advantages in some cases.