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Comprehensive Summary Salimabromide, a unique and scarce marine tetracyclic polyketide, was synthesized in both racemic and optically active forms. A novel carboxylic acid‐directed method for tandem oxidative difunctionalization of olefins was developed, whereby the formation of bridged butyrolactone and enone moieties occurs concurrently. Density functional theory (DFT) calculations indicate that this reaction follows a [3+2] process rather than the [2+2] process. In the meantime, the distinctive benzo‐fused [4.3.1] carbon skeleton and highly hindered vicinal quaternary stereocenters were simultaneously constructed through a challenging intramolecular Giese‐Baran radical cyclization. Furthermore, deuterium kinetic isotopic effects were utilized to enhance the efficacy of this pivotal step. This represents a new illustration of the application of kinetic isotope effects in natural product synthesis. Then, the short asymmetric synthesis of (+)‐salimabromide (13 or 15 steps) was accomplished by combing this method with rhodium‐catalyzed enantioselective hydrogenation of a cycloheptenone derivative (97% ee) or conjugate addition of an aryl boronic acid with 2‐cyclohepten‐1‐one (> 99% ee). [ABSTRACT FROM AUTHOR]

Due to the innate highly reactive properties and short life‐time, organic free radicals can often serve as promoters or intermediates to engage in various radical transformations, which are often otherwise difficult to access by ionic pathway‐based mechanisms. With the evolvement of radical chemistry, chiral radical catalyzed‐transformations have recently emerged as an attractive and robust platform for synthesis of chiral molecules of interest. Herein, we highlight several creative and strategic advances in chiral radical catalyst design, cyclization reaction achievements, and future challenges. Key Scientists: In the 1980s, some pioneering studies by Feldman and Oshima revealed that the thiyl radical could catalyze cyclization of vinylcyclopropane with alkenes, providing access to racemic cyclopentanes. In 1996, Brian P. Roberts reported an interesting enantioselective hydrosilylation of prochiral alkenes by using thioglucose‐derived chiral thiyl radical catalysts. Since then, chiral radical catalysis has become an emerging and promising catalytic strategy in organic synthesis. However, this field has not been extensively explored further until the Maruoka group in 2014 achieved the asymmetric C—C bond formation by employing a newly designed indanol core‐based chiral thiyl radical catalyst. In this protocol, an enantioselective radical cyclization of vinylcyclopropanes with electron‐rich alkenes was developed. In 2020, Chen and Xiao disclosed a nitrogen radical‐catalyzed version of this reaction. Later, this strategy was further expanded to metalloradical catalyzed asymmetric radical cascade cyclization reactions by Zhang in 2021. Later on, Wang, Fu and Zhang et al. described a novel class of boryl radical‐catalyzed asymmetric radical cycloisomerization reactions, further showcasing enormous synthetic potential of chiral radical catalysis. This Emerging Topic has focused on asymmetric radical cyclization reactions involving diverse chiral radical catalysts. [ABSTRACT FROM AUTHOR]

Furanocoumarins are attractive targets in the synthetic organic and medicinal chemistry field because of their structural diversity and interesting biological properties. Herein, we describe the synthesis of furanocoumarin natural products from common furanocoumarin skeletons. A key step was a novel intramolecular radical cyclization onto nitrile to synthesize angular and linear franocoumarins, which was optimized by reacting iodocoumarin derivatives in the presence of (Me3Si)3SiH and oxygen. These compounds served as intermediates in the syntheses of vaginidiol, vaginidin, oroselol, multivittan D, gaudichaudine, oreoselone, peucedanin, and smyrindiol, successfully demonstrating the versatility of the intermediates and utility of the radical cyclization method for accessing furanocoumarin natural products. [ABSTRACT FROM AUTHOR]

Synthesis of poison dart frog indolizidine alkaloids (−)‐209D, (−)‐209B and (−)‐223V were accomplished, with a common tricyclic lactone skeleton as the starting compound, in overall yields of 8.8 %, 5.5 %, and 5.2 %, respectively. The construction of the C7−C8 bond in the synthesis of 209D involves simple ring closure metathesis and hydrogenation reactions. However, in the synthesis of 209B and 223V, the C7−C8 bond and the stereochemistry of C8, is achieved through radical cyclization reactions controlled by allylic 1,3‐strain. Cleavage of the excess carbon on the C5 for all the related intermediates were done by Barton decarboxylation protocol. Reduction of the corresponding indolizidin‐3‐ones by LAH completed the total synthesis of these three target molecules. The quantum mechanics calculations were performed on α‐amidyl carbon radical intermediates to account for the observed diastereomeric ratio (~9 : 1) of the key Barton decarboxylation step. Ultimately, the synthesis of 3‐epi‐(−)‐223AB was accomplished in 51.6 % through the cuprate addition to the activated lactam of a late intermediate in the synthesis of (−)‐167B. [ABSTRACT FROM AUTHOR]

Isocyanide is a promising synthetic reagent not only as a one-carbon homologation reagent but also as a nitrogen source for nitrogen-containing molecules. Because of their isoelectronic structure with carbon monoxide, isocyanides also react with nucleophiles, electrophiles, carbon radicals, and transition metal reagents, and are widely used in organic synthesis. On the other hand, the use of isocyanides in reactions with heteroatom radicals is limited. However, the reaction of isocyanides with heteroatom radicals is a promising synthetic tool for the construction of nitrogen-containing organic molecules modified with a variety of heteroatoms. In this Perspective, we review the addition and cyclization reactions of heteroatom radicals with isocyanides and discuss the synthetic prospects of the reaction of isocyanides with heteroatom radicals.

An iron(III)‐promoted radical fluoroalkylation of o‐alkenylaryl isocyanides has been developed using readily available perfluoroalkyl iodides as fluoroalkyl source. This cyclization reaction features broad substrate scope and provides a simple and efficient approach for regioselective construction of biologically important 2‐fluoroalkylated quinolines in 38–81 % yields. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Pseudolaric acids are a family of diterpenoid natural products that exhibit a broad spectrum of biological activities. The main structural feature of their framework is a trans‐fused perhydroazulene bearing a bridged lactone positioned at the junction of the rings. Herein, we have developed a radical cyclization strategy that allows flexible tuning of the cyclization process through diverse silicon substitutions on the substrates. This strategy can assist in constructing a series of skeletons with structural resemblance to pseudolaric acids and expedites the construction of the bridged lactone. Finally, it facilitates the synthesis of the entire skeletal structure of the pseudolaric acid family of natural products, excluding the B‐ring functionalization. [ABSTRACT FROM AUTHOR]

Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one‐carbon introduction and ring expansion operations, we have successfully converted cephalotane‐type C18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid‐type C19 norditerpenoids and intact cephalotane‐type C20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13‐oxo‐cephinoid H, 7‐oxo‐cephinoid H, fortalpinoid C, 7‐epi‐fortalpinoid C, cephanolide E, and 13‐epi‐cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between β‐oxo esters and β‐substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family. [ABSTRACT FROM AUTHOR]

The given text is a scientific research article that explores the synthesis and characterization of various compounds using different reactions and starting materials. The compounds synthesized include isoxazolines, pyrazolines, isoxazolidines, cinnamyl- and indenyl-linked moieties, and 2-phosphorylated 2,5-dihydrofurans. The document provides detailed information on the reaction conditions, yields, physical properties, and spectroscopic data of the synthesized compounds. The information presented can be useful for researchers studying the synthesis and characterization of these compounds. [Extracted from the article]

Cyclobutanes with a gem‐dimethyl group are common motifs in natural products. However, strategies for constructing enantioenriched gem‐dimethyl cyclobutanes are still underdeveloped. Herein, we report an enantioselective approach to synthesize a broad group of chiral 2,3‐disubstituted cyclobutanones through sequential 1,4‐conjugate addition/trapping/cross‐coupling of readily available cyclobutenones. The intermediate 2‐bromocyclobutanone provides a valuable synthetic handle for further coupling transformations. In addition, this strategy was successfully utilized to synthesize gem‐dimethyl cyclobutane‐containing natural products, including (+)‐β‐caryophyllene, (−)‐raikovenal, (−)‐1β,9αH‐5‐linoleoyloxy‐4,5‐secocaryophyllen‐4‐one, and (−)‐rumphellanones A−C. [ABSTRACT FROM AUTHOR]

Unique chemical structures that are often characteristic of biologically active natural products are often created by oxidative cyclizations. Many of these reactions are catalysed by 'non‐canonical' or 'thwarted' iron oxygenases that appear to involve long‐lived radicals. This perspective summarizes our group's efforts to mimic these biosynthetic transformations for the synthesis of highly oxidized dibenzocyclooctadiene lignan natural products using redox neutral photocatalysis. We describe the evolution of this research program, which hinges on the use of Okada's redox active ester, and show how multiple factors control the fate of the resulting radicals. [ABSTRACT FROM AUTHOR]

Ligands are at the heart of coordination chemistry. They conjure the magic of transition metals expressed in organometallic catalysis. Phosphine or P-ligands have found vast utility in transition metal chemistry, though demanding tedious synthesis. Several N, S-based ligands also find application in organometallic chemistry. Oximes are easily derived from aldehydes and ketones by simple reactions with hydroxylamine. Thus, an extensive library of oximes is available with different structural and electronic variations essential for coordination chemistry and catalysis. Several compounds with complex structural features, unavailable for phosphorous ligands, can be readily converted into active oxime ligands in a single derivatization step. Oxime ligands and metal complexes are applied in synthesizing diverse organic molecules and thus versatile ligands in organotransition metal chemistry. [ABSTRACT FROM AUTHOR]

This article explores the use of N-Heterocyclic carbene (NHC) catalysis and photoredox catalysis in organic chemistry. It focuses on the less explored area of radical NHC catalysis and discusses the combination of NHC catalysis with photoredox catalysis to achieve reductive and oxidative pathways. The article emphasizes the generation of nitrogen-centered radicals and their significance in the synthesis of nitrogen-containing heterocycles. It concludes by presenting a specific example of aminoacylation of alkenes using cooperative NHC/photoredox catalysis, highlighting its potential applications in the synthesis of N-heterocycles. [Extracted from the article]

This article discusses the development of sustainable synthetic methods for the production of Active Pharmaceutical Ingredients (APIs) and other materials. The focus is on the synthesis of benzimidazole-fused phenanthridines, a class of heterocyclic compounds with various applications. The authors describe a new intramolecular radical C-N coupling reaction mediated by N-iodosuccinimide (NIS) in trifluoroethanol (TFE), which allows for the formation of these compounds in high yields. The document provides detailed procedures for the synthesis and characterization of specific compounds using this method, including their physical properties and spectroscopic data. The supporting information for the article is available online and includes control experiments, characterization data, and NMR spectra. [Extracted from the article]

Despite the unique reactivity of vitamin B12 and its derivatives, B12‐dependent enzymes remain underutilized in biocatalysis. In this study, we repurposed the B12‐dependent transcription factor CarH to enable non‐native radical cyclization reactions. An engineered variant of this enzyme, CarH*, catalyzes the formation γ‐ and δ‐lactams through either redox‐neutral or reductive ring closure with marked enhancement of reactivity and selectivity relative to the free B12 cofactor. CarH* also catalyzes an unusual spirocyclization by dearomatization of pendant arenes to produce bicyclic 1,3‐diene products instead of 1,4‐dienes provided by existing methods. These results and associated mechanistic studies highlight the importance of protein scaffolds for controlling the reactivity of B12 and expanding the synthetic utility of B12‐dependent enzymes. [ABSTRACT FROM AUTHOR]

An iodine‐mediated radical cyclization of o‐vinylaryl isocyanides with disulfides or diselenides was developed. The atom‐economic reaction provides a method for regioselective construction of the 2‐chalcogenated quinolines in 42–93% yields by incorporation of both chalcogen atoms of disulfides or diselenides into quinolines. [ABSTRACT FROM AUTHOR]

Phenanthridines are a privileged heterocyclic compound that exists in many natural products and has been known to exhibit a variety of pharmacological properties. In the last few decades, an incredible development has taken place to synthesise this scaffold. In this regard, 2‐isocyanobiphenyl has become one of the most exploited substrates that allow the direct formation of phenanthridine derivatives under various novel and conventional methods. The present review provides an overview of synthetic approaches for the preparation of phenanthridine, and their derivatives form 2‐isocyanobiphenyls′′. [ABSTRACT FROM AUTHOR]

A visible‐light‐driven approach towards phenanthridin‐6(5H)‐one and carbazole rings synthesis under transition‐metal‐free conditions is here reported. Phenanthridinones and carbazoles are synthesized through an intramolecular arylation of the corresponding N‐(2‐halobenzyl)‐N‐methylanilines or N‐substituted‐N‐phenyl anilines using KOtBu as base in dimethyl sulfoxide (DMSO) at room temperature (rt), employing blue light emitting diodes (LEDs) as the light source. The reaction proceeds through photo‐ and base‐promoted homolytic aromatic substitution via photoinduced electron transfer mechanism and it exhibits good tolerance to different functional groups, resulting in good to very good yields (up to 86 %). [ABSTRACT FROM AUTHOR]

[1] After two decades, GDA was isolated from another dinoflagellate, I Alexandrium hiranoi i , and its full structure and relative configuration were reported by Murakami et al. [2][3] GDA was also isolated from I Alexandrium monilatium i by Moeller et al. in 2006. The structure of GDA consists of six ether rings, including 6,6-spiroketal, four I exo i -methylenes, and 17 chiral centers. Keywords: radical cyclization; Pummerer rearrangement; cyclic ether; goniodomin A EN radical cyclization Pummerer rearrangement cyclic ether goniodomin A 1795 1798 4 08/29/23 20230915 NES 230915 Graph Goniodomin A (GDA, Figure 1), a 32-membered polycyclic macrolide, was reported by Sharma et al. in 1968 as an unidentified structural metabolite isolated from dinoflagellates of the I Alexandrium i genus. [Extracted from the article]

In this mini-review, we present our concepts for designing multicomponent reactions with reference to a series of sequential radical reactions that we have developed. Radical reactions are well suited for the design of multicomponent reactions due to their high functional group tolerance and low solvent sensitivity. We have focused on the photolysis of interelement compounds with a heteroatom–heteroatom single bond, which readily generates heteroatom-centered radicals, and have studied the photoinduced radical addition of interelement compounds to unsaturated compounds. First, the background of multicomponent radical reactions is described, and basic concepts and methodology for the construction of multicomponent reactions are explained. Next, examples of multicomponent reactions involving two interelement compounds and one unsaturated compound are presented, as well as examples of multicomponent reactions involving one interelement compound and two unsaturated compounds. Furthermore, multicomponent reactions involving intramolecular cyclization processes are described. [ABSTRACT FROM AUTHOR]

[2] Following our interest in Ugi reactions and the use of the latter in radical reactions, [9] we envisioned that a variant of the intramolecular Buchner reaction could be devised using a twofold Mn(III) oxidation of malonic acid derivatives. Keywords: manganese acetate; Ugi reaction; radical cyclization; cyclopropanation EN manganese acetate Ugi reaction radical cyclization cyclopropanation 1581 1586 6 07/31/23 20230815 NES 230815 Graph Already known in the 19 SP th sp century, the Buchner ring expansion of aromatic compounds involves as key steps the ring opening of transient cyclopropanes formed under addition of carbenes onto the aromatic rings. [9] As the two cyclization steps which are required to reach the expected Buchner-type cyclopropanes entail a global 4-electron oxidation, at least 4 equiv of Mn(OAc) SB 3 sb had to be used. [Extracted from the article]

The upsurge in interest in the development of methodologies for the synthesis of sulfur‐containing compounds via the use of visible‐light has been established as a sustainable tool in organic chemistry. Particularly, visible‐light mediated C−S bond formation has gained popularity due to its operational simplicity, minimized by‐products, easy handling, mild reaction conditions, etc. Photochemistry not only provides a sustainable way to synthesize complex molecules but also has the ability to overcome many challenges which are difficult to attain by conventional thermal pathways. Owing to the biological importance of sulfur‐containing compounds, the present review focused on the C−S bond formation under metal‐free conditions mediated by visible‐light. The objective of the current review is to bring out the unearthing collection regarding C−S bond formation via photoredox catalysis. For better understanding, the review is categorized according to the mode of reactions viz, C−S bond formation via difunctionalization of alkenes and alkynes, C−S bond formation via C−H functionalization, and C−S bond formation via radical cyclization. All the reactions in each of the sections are described with selected examples with a proper explanation of the proposed mechanism. [ABSTRACT FROM AUTHOR]

A mild, efficient, photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity in metal-free conditions, using low-cost Rose Bengal as a catalyst and sustainable air as a terminal oxidant at room temperature and providing the desired products in moderate to good yields. [ABSTRACT FROM AUTHOR]

Amide‐type 1,6‐enyne compounds, readily available from unsaturated N‐Boc acyl amide and propargylic mesylate, underwent a radical cascade reaction upon treatment with Bu3SnH, giving bicyclic 2,3‐dihydrostannole lactams in good yields. Regioselectivity of the reaction depended on the presence or absence of alkyne substituents; alkyl‐substituted internal alkynes selectively gave 2,3‐dihydrostannoles in good yields, while terminal alkynes gave a mixture of piperidine and 2,3‐dihydrostannole. The reaction promoted the radical cascade process starting from the addition of tin radical to the alkenyl terminal followed by 5‐exo‐dig radical cyclization. The resulting vinyl radical attack the tin atom, and direct radical substitution progressed, giving bicyclic 2,3‐dihydrostannoles in good yields. [ABSTRACT FROM AUTHOR]

A novel method for synthesizing 3‐arylselanyl benzothiophenes through visible‐light‐mediated radical cyclization was developed. Diaryl selenides were used as aryl selenium sources under the irradiation of white‐light‐emitting diodes (5 W). The reactions were conducted under mild conditions, where the desired products were obtained at room temperature (23 °C) without the need for catalysts or additives. This simple method allows for an efficient route for synthesizing benzothiophene derivatives, which are crucial scaffolds in organic synthesis. [ABSTRACT FROM AUTHOR]

A novel metal-free photoredox-catalyzed cyclization reaction of N-aryl acrylamide is herein reported that provides synthetically valuable oxindole derivatives through the bis-mediation of H2O and aldehyde. In this work, sustainable visible light was used as the energy source, and the organic light-emitting molecule 4CzIPN served as the efficient photocatalyst. The main characteristics of this reaction are environmentally friendly and high yields. [ABSTRACT FROM AUTHOR]

A mild and versatile cerium‐mediated decarboxylative strategy for sequential alkylation/cyclization was developed for the synthesis of quaternary oxindoles and benzimidazo[2,1‐a]isoquinolin‐6(5H)‐ones via photoinduced‐LMCT. This operationally simple procedure relies on inexpensive and feedstock carboxylic acids as alkyl radical surrogates and aerial molecular oxygen as the terminal oxidant. This mild and atom economical protocol showed viability with a wide range of alkyl carboxylic acids (1° to 3° acids) as coupling partners and also allows the late‐stage modification of pharmaceutically‐important acids. Mechanistic studies revealed the reaction to follow radical pathway, while the decarboxylative event was studied by in situ FTIR. [ABSTRACT FROM AUTHOR]

The cycloaddition reaction of o‐diisocyanoarenes with interelement compounds under light is a very important reaction system to clarify whether this reaction proceeds by radical cyclization or by aza‐Bergman cyclization. In this study, a series of diphosphines with phosphorus‐phosphorus single bonds were selected as interelement compounds, and their cycloaddition reactions with o‐diisocyanoarenes under light were investigated in detail to achieve a novel photoinduced synthesis of bisphosphinated quinoxalines via the radical cyclization pathway. In addition, the photoinduced reaction of diphosphines with isocyanides having o‐functional groups such as cyano and ethenyl groups allowed us to elucidate the reaction pathway and product selectivity of this bisphosphination. Furthermore, the one‐pot synthesis of PdII‐quinoxaline complex was successfully achieved by applying the developed reaction. [ABSTRACT FROM AUTHOR]

Ent‐kaurenes consist of an ABC‐ring based on a trans‐anti‐hydrophenanthrene skeleton and a D ring with an exomethylene. Highly oxygen‐functionalized ent‐kauren‐15‐ones have promising antiinflammatory pharmacological activity. In this study, we developed a novel diastereoselective synthesis of trans‐anti‐hydrophenanthrenes via a Ti‐mediated reductive radical cyclization. We also demonstrated the applicability of this method by developing the first total synthesis of (±)‐kamebanin (longest linear sequence; 17 steps, overall yield; 6.5 %). Furthermore, this synthesis provided a formal semi‐pinacol rearrangement for the construction of the quaternary carbon at C8 and a novel Thorpe‐Ziegler‐type reaction for the construction of the D‐ring. [ABSTRACT FROM AUTHOR]

An alkoxycarbonyl radical cyclization-cross-coupling cascade has been developed that allows functionalized γ-butyrolactones to be prepared in one step from simple tertiary alcohol-derived homoallylic oxalate precursors. The reaction succeeds with aryl and vinyl electrophiles and is compatible with heterocyclic fragments in both coupling partners. This chemistry allows for the rapid construction of spirolactones, which are of interest in drug discovery endeavors.

An efficient radical cyclization of suitably functionalized ynamides to nitrogen-containing heterocycles is reported. Upon reaction with tributyltin hydride in the presence of catalytic amounts of AIBN in toluene at 80 °C, a range of ynamides bearing a N -iodopropyl chain could be smoothly cyclized, in a highly regio- and stereoselective manner, to the corresponding 2-arylidenepyrrolidines in good to excellent yields. The exocyclic double bond was in addition shown to be an excellent anchor for further chemical diversification and the generality of this radical cyclization could be highlighted by its extension to the synthesis of other nitrogen heterocycles including piperidines, azepanes, pyrazolidines and hexahydropyridazines. [ABSTRACT FROM AUTHOR]

Samarium is an efficient reducing agent, a radical generator in cyclization and a cascade addition reaction. Interestingly, samarium metal has crucial impact on numerous C-C and C-X (X = hetero atom) bond forming transformations. It has been established as an exceptional chemo-selective and stereoselective reagent. The reactivity of the samarium catalyst/reagent is remarkably enhanced in the presence of various additives, ligands and solvents through effective coordination and an increase in reduction potential. It has inherent character to act as electron donor for a wide range of transformations including the asymmetric version of various reactions. This review accentuates the developments in samarium-mediated/catalyzed asymmetric organic synthesis over the past 12 years, where the chirality has been induced from ligand, a nearby asymmetric center within the substrate or through coordination directed stereospecific reactions. [ABSTRACT FROM AUTHOR]

We report a new iron‐catalyzed I/Zn‐exchange allowing to convert primary or tailored secondary alkyl iodides into the corresponding alkylzinc iodides. In the presence of a remote double bond at position 5, diastereoselective ring closures are observed. Quenching of these zinc reagents, after transmetalation to copper species (with CuCN ⋅ 2LiCl) or under Pd‐catalysis, with typical electrophiles (allyl bromides, acid chlorides or aryl iodides) gave various polyfunctional products. [ABSTRACT FROM AUTHOR]

A method for radical cyclization of N -methacryloyl-2-arylbenzoimidazoles with nitriles, ketones, and tert -butyl nitrite (TBN) for the preparation of benzimidazo[2,1- a ]isoquinolin-6(5 H)-ones with the advantage of mild reaction conditions, excellent functional group compatibility, and broad substrate scope is reported. The present strategy has favorable characteristics: (1) the use of cheap metal catalysis; (2) N -radical-initiated cyclization of N -methacryloyl-2-arylbenzoimidazoles; and (3) rare example of radical C(sp3)–H functionalization in this cyclization. [ABSTRACT FROM AUTHOR]

In this mini-review, we present our concepts for designing multicomponent reactions with reference to a series of sequential radical reactions that we have developed. Radical reactions are well suited for the design of multicomponent reactions due to their high functional group tolerance and low solvent sensitivity. We have focused on the photolysis of interelement compounds with a heteroatom–heteroatom single bond, which readily generates heteroatom-centered radicals, and have studied the photoinduced radical addition of interelement compounds to unsaturated compounds. First, the background of multicomponent radical reactions is described, and basic concepts and methodology for the construction of multicomponent reactions are explained. Next, examples of multicomponent reactions involving two interelement compounds and one unsaturated compound are presented, as well as examples of multicomponent reactions involving one interelement compound and two unsaturated compounds. Furthermore, multicomponent reactions involving intramolecular cyclization processes are described.

Electro‐reductive radical cyclisation of aryl halides affords the corresponding hetero‐ and carbo‐cycles in an undivided flow reactor equipped with steel and carbon electrodes using an organic mediator. A dissolving metal anode is not needed, and the mediator can be employed in a sub‐stoichiometric amount (0.05 equiv), increasing the practical utility of cathodic radical cyclisation. The methodology is applied to O‐, N‐, and C‐tethers, yielding tricyclic fused and spiro systems. In the absence of mediator, the major pathway is hydrogenolysis of the C−X bond, a 2 e− process occurring at the cathode. Predominance of the radical pathway in presence of a strongly reducing mediator (M) is consistent with homogeneous electron‐transfer in a reaction layer detached from the cathode surface, where the flux of M.− leaving the electrode is such that little aryl halide reaches the cathode. [ABSTRACT FROM AUTHOR]

We report the preparation of nor‐bisabolyl epoxide 13 and its use as a common biomimetic intermediate for the synthesis of nor‐sesquiterpenoids. Through a cationic cyclization cascade pathway, we prepared nor‐isozizaenol 25, ultimately constituting an eight‐step access to this complex sesquiterpenoid from inexpensive and abundant starting materials. Using a radical cyclization cascade pathway, we prepared nor‐cedryl alcohol 26 from the same intermediate. Derivatization of these two products led to the discovery of two potent woody odorants of interest in perfumery. [ABSTRACT FROM AUTHOR]

O‐substituted derivatives of N‐hydroxyphthalimide (NHPI) have attracted much attention recently as synthetically available, stable, and convenient reagents for the generation of free radicals under mild conditions. The single‐electron reduction by a photoredox catalyst or another reagent results in the N−O bond cleavage of an NHPI derivative with the release of free radicals that undergo selective synthetic transformations. Whereas N‐acyloxyphtalimides (NHPI esters) are well known as a convenient C‐radical source due to the facile one‐electron reduction followed by the decarboxylation, N‐alkoxyphtalimides are much less studied as radical precursors. The present review shows that N‐alkoxyphtalimides are effective reagents for free‐radical transformations starting from the generation of alkoxy free radicals. Visible light induced reactions are discussed first, these processes are classified according to the way how intermediate alkoxy radicals transformed to C‐centered radicals: via hydrogen atom transfer to oxygen atom (HAT, including 1,5‐HAT, 1,2‐HAT, and intermolecular HAT) or via β‐scission. Other photochemical radical reactions of alkoxyphthalimides and non‐photochemical tin‐mediated processes are discussed separately. [ABSTRACT FROM AUTHOR]

Here we present a transition‐metal‐free radical cyclization of 2‐arylbenzoimidazoles with unactivated alkanes. By using di‐tert‐butyl peroxide (DTBP) to promote the C(sp3)−H bond functionalization, this approach enables assembly of various benzimidazo[2,1‐a]isoquinolin‐6(5H)‐ones in aqueous media. This strategy can not only well tolerate a wide range of cyclic alkanes, straight‐chain alkanes, toluene derivatives, as well as pharmaceutical molecule eudesmol, but also provides an approach for the functionalization of unactivated C(sp3)−H bonds in aqueous media under transition‐metal‐free systems. [ABSTRACT FROM AUTHOR]

A wide range of derivatives with new pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline skeleton was synthesized by free-radical intramolecular cyclization of o-bromophenyl-substituted pyrrolylpyridinium salts using the (TMS)3SiH/AIBN system. The cyclization provides generally good yields of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline hydrobromides having no additional radical-sensitive substituents. The free bases can be obtained from the synthesized hydrobromides in quantitative yield by basification at room temperature. The selectivity control of intramolecular arylation was achieved by replacing the halogen: the use of 1-(2-(ortho-bromophenyl)-4-(ortho-iodophenyl)pyrrol-3-yl)pyridinium bromide makes it possible to obtain a monocyclization product, and the bicyclization product from the dibromo derivative. The procedure is also applicable to obtain 3-arylpyrido[2,1-a]pyrrolo[3,2-c]isoquinoline derivatives including 2-unsubstituted skeletons that are inaccessible via Pd-catalyzed cyclization.

In this work, we present the details of the first unified chemical synthesis of cephalotaxus diterpenoids with three distinct carbon skeleton structures. Drawing on our previous synthesis of cephalotane-type C18 dinorditerpenoid and inspired by the proposed biosynthetic synthesis pathway, we formulated a biosynthetic reversed chemical synthetic strategy. This strategy facilitated the conversion of C18 dinorditerpenoid into troponoid-type C19 norditerpenoid and intact cephalotane-type C20 diterpenoid through pivotal one-carbon introduction and ring expansion reactions. In the synthesis of troponoid-type C19 norditerpenoid, we utilized TMSCHN 2 as one-carbon unit and meticulously examined the selective regulatory effect of halogen substituents in ring expansion and rearrangement reactions. This endeavor culminated in the successful synthesis of natural product molecules within this subclass, notably including cephinoid H and fortalpinoid C, marking the first chemical total synthesis in this line of research. In the investigation of intact cephalotane-type C20 diterpenoid synthesis, while adhering to the overall synthesis strategy, we initially pursued a ring expansion before carbon introduction approach, which proved unsuccessful. Subsequently, we explored a synthetic route of introducing carbon first and then expanding the ring, leading to a successful outcome and resulting in the first chemical total synthesis of the representative molecule cephanolide E within this subclass. Various challenges such as establishing crucial quaternary carbon stereocenters, selecting appropriate one-carbon units, and controlling ring expansion reactions were effectively addressed throughout this process. Moreover, enantioselective synthesis of natural products within this family was achieved through the development of asymmetric Michael reactions. A detailed research summary is presented for introducing the unified total synthesis of three subgroups of cephalotaxus diterpenoids, with a novel synthetic route possessing a reverse order with potential biosynthetic route. The troponoid-type C19 norditerpenoids cephinoid H and fortalpinoid C could be synthesized from cephalotane-type C18 dinorditerpenoid-cephanolide B through regioselective ring expansion modulated by introducing a chlorine atom at the C15 site. For intact cephalotane-type C20 diterpenoids, we develop two synthetic routes to explore their syntheses from cephalotane-type C18 dinorditerpenoid-cephanolide B, involving ring expansion/C17-introduction and its reverse process. The first synthetic route is unsuccessful due to the great difficulty of C17-introduction and the first total synthesis cephalotane-type C20 diterpenoid cephanolide E is finally realized via the second synthetic route. [Display omitted] [ABSTRACT FROM AUTHOR]

An efficient photo‐induced direct oxidative radical cascade cyclization of N‐arylacrylamides with aliphatic alcohols at ambient temperature was developed. The present reaction exhibits a wide substrate scope, and various valuable oxindoles can be effectively accessed through the direct sp3 C−H functionalization of alcohols, ethers, cyclohexane, toluene and acetonitrile. Importantly, this cascade reaction proceeds photocatalyst‐free, at room temperature, utilizes readily available starting materials, and has a broad substrate scope. [ABSTRACT FROM AUTHOR]

Total syntheses of two Isodon diterpenes, isorosthin L and isoadenolin I, are reported. The synthetic strategy features a quick assembly of two simple building blocks through a diastereoselective intermolecular aldol reaction and a subsequent radical cyclization for efficient construction of a rather complex advanced intermediate bearing a quaternary stereocenter present in all Isodon diterpenes. Oxidative cleavage of the C−C bond in the cyclopentane enabled the conversion to a lactone moiety which is desired for the construction of the molecular skeleton through reductive coupling with an aldehyde carbonyl group. [ABSTRACT FROM AUTHOR]

A photocatalyzed and highly efficient trifluoromethylation of N -arylvinylsulfonamides using commercially available CF3 SO2 Cl as the trifluoromethyl radical source under blue LEDs is reported. The reaction proceeds through radical cyclization under mild conditions. An investigation of the substrate scope is performed to establish a general, synthetically useful protocol for the synthesis of novel trifluoromethylated 1,3-dihydrobenzo[ c ]isothiazole 2,2-dioxides in moderate to high yields. This method is also successfully applied for the synthesis of difluoromethylated and trifluoroethylated 1,3-dihydrobenzo[ c ]isothiazole 2,2-dioxides in good to excellent yields. [ABSTRACT FROM AUTHOR]

Coumarins (2H‐1‐benzopyran‐2‐one) are a class of natural products extracted from plant with a broad range of biological activities like antitubercular, anti‐inflammatory, anticancer, anticonvulsant, neuroprotective, antiviral, antifungal, antibacterial, antihyperglycemic, anticoagulant, antihypertensive, antiadipogenic, and antioxidant, effects. Therefore, the synthesis of coumarin and its derivatives has become amongst the most attractive compounds over the last two decades in the growth of improved synthetic methods to form various coumarins derivatives. Amongst the reported methods for the construction of coumarins, the pendant arylpropiolate scaffolds served as a highly appealing precursor for coumarins in a single step. This review article describes recent updates on the construction of coumarins using arylpropiolate as substrates. [ABSTRACT FROM AUTHOR]

A variety of chroman-4-ones bearing phosphine oxide motifs were conveniently synthesized from readily available diphenylphosphine oxides and alkenyl aldehydes via a metal-free tandem phosphinoylation/cyclization protocol. The reaction utilizes K2S2O8 as oxidant and proceeds in DMSO/H2O at environmentally benign conditions with a broad substrate scope and afforded the title compounds in moderate yields.

Isocyanide is a promising synthetic reagent not only as a one-carbon homologation reagent but also as a nitrogen source for nitrogen-containing molecules. Because of their isoelectronic structure with carbon monoxide, isocyanides also react with nucleophiles, electrophiles, carbon radicals, and transition metal reagents, and are widely used in organic synthesis. On the other hand, the use of isocyanides in reactions with heteroatom radicals is limited. However, the reaction of isocyanides with heteroatom radicals is a promising synthetic tool for the construction of nitrogen-containing organic molecules modified with a variety of heteroatoms. In this Perspective, we review the addition and cyclization reactions of heteroatom radicals with isocyanides and discuss the synthetic prospects of the reaction of isocyanides with heteroatom radicals., (Copyright © 2024, Ogawa and Yamamoto.)

Novel acrylamide and methacryloyl carrying piperazine-dihydrofuran derivatives (3a-p) were designed and obtained from radical cyclizations of unsaturated piperazine derivatives (1a-f) with 1,3-dicarbonyl compounds (2a-c) mediated by Mn(OAc)3. Obtained compounds were characterized by spectroscopic methods. In vitro AChE inhibitory activites of 3a-p were evaluated against AChE (Acetylcholinesterase) by Ellman method and test results showed that 3a, 3c, 3j, and 3l are the most active AChEI's (AChE inhibitors) of our work with IC50 (half-maximal inhibitory concentration) values of 2.62, 5.29, 1.17, and 3.90 µM, respectively. Furthermore, ligand-protein interactions and inhibitory activity mechanisms of 3a and 3j were investigated by molecular docking. Finally, in silico molecular property and ADME predictions (absorption, distribution, metabolism and excretion) of potential AChEI's were predicted by PreADMET and Molinspiration webservers. It can be concluded that the lead compound 3j show excellent inhibiton and satisfactory druglike characteristics. [ABSTRACT FROM AUTHOR]