The development of operationally simple and environmentally benign synthetic strategies for constructing phosphorus-substituted heterocycles is highly valuable in organophosphorus chemistry. Herein, we report a straightforward and green radical cascade cyclization of diphenylphosphine oxide with isocyanides or heteroarenes for the synthesis of phosphorylated heteroarenes with high atom economy. With air as a green oxidant and ethanol as the solvent, without additional oxidants or bases, this one-pot protocol exemplifies the principles of green chemistry, enabling the construction of C-P and C-C bonds using an inexpensive, commercially available and low-toxicity catalyst. Studies on electron paramagnetic resonance and control experiments indicated that manganese(III) salt and O2 act in concert to achieve radical cascade cyclization, with superoxide radical anion (O2•-) contributing to this reaction.

C─H activation of toluene generates a benzyl radical that undergoes C─C coupling, converting an abundant solvent into carbon building blocks. A major challenge, however, is to direct the highly reactive benzyl radical to add regioselectively to a multi-π system in a way that initiates a cascade leading to complex products. Here, we achieved this goal for the first time, to our knowledge, and demonstrated that polysubstituted indene derivatives can be efficiently obtained through a three-component cascade radical cyclization of 1,5-enynes with toluene solvent and benzoic acids in the presence of a copper catalyst and TBHP oxidant. Notably, the same indene products were also obtained when aldehydes were used in place of benzoic acids. Our combined experimental and computational investigations fully elucidated the reaction mechanism, showing that it proceeds through a Cu(I/II/III) redox cycle. This study further revealed that benzyl radicals are generated at the outset of the reaction but are highly reactive and prone to deactivation unless they undergo rapid and regioselective addition to the multi-π system. We show that these requirements are satisfied only when both terminal carbons of the alkene moiety in the 1,5-enyne bear strong electron-withdrawing substituents such as CN or CO2Me.

Couple-close as a synthetic paradigm has the potential to change the way that synthetic organic chemists approach cyclic scaffold construction. One class of cyclic molecules that has been increasingly sought after is semisaturated cyclic scaffolds, whose specific blend of Csp2- and Csp3-hybridized components confers distinct properties to these species. However, existing methods to construct these scaffolds are limited, often relying on arene saturation or annulations that require lengthy de novo syntheses. Herein, we describe a unified and highly modular couple-close strategy for the synthesis of semisaturated scaffolds. This approach installs bifunctional linkers onto aromatic rings through a range of bond-forming reactions, and subsequent cyclization furnishes semisaturated bicyclic adducts. Key to this approach is a mechanistically distinct cobalt-catalyzed dehydrogenative radical cyclization that proceeds efficiently even on electronically unbiased arenes, enabling a broad substrate scope under mild reaction conditions.

Autoxidation pathways and stability of methyl linolenate (MLN) and methyl linoleate (ML) were compared in bulk oil and oil-in-water (O/W) emulsions under dark, sealed storage at 37 °C, using peroxide value (PV), GC, HPLC-MS/MS, and nuclear magnetic resonance (NMR) for characterization. Both esters rapidly entered the oxidation propagation stage in both systems, initially forming cis-trans monohydroperoxides (ZEMHP) via hydrogen abstraction, which was more favorable in the emulsion system. Notably, high proportions of secondary hydroperoxides formed concurrently, increasing with oxidation: MLN initially produced dominant bicyclic endoperoxides (BCEHP) and minor monocyclic endoperoxides, summing to 34.1% (CHPs at 95.6 mmol/kg); ML initially formed dominant trans-trans monohydroperoxides (EEMHPs), summing to 45.1% (CHPs at 86.7 mmol/kg), and epoxy hydroperoxides at the late oxidation stage. Moreover, MLN exhibited higher apparent oxidation stability than ML in emulsions, which might be due to higher hydrogen abstraction activation energies for cyclic peroxyl radicals (PRs) to form cyclic endoperoxides calculated by DFT calculations.

An asymmetric total synthesis of (+)-melicolone K is described for the first time. The strategy features a late-stage programmed C-H functionalization, which comprises a Rh(II)-catalyzed γ-C(sp3)-H amination and a newly formed cyclic sulfamate ester-directed γ-C(sp3)-H prenylation through a formal (4 + 2) cycloaddition/reductive ring-opening process. By incorporation of a Sharpless asymmetric dihydroxylation, a Wolff ring contraction, and a Ti(III)-mediated radical cyclization, our approach rendered concise and efficient access to this flagship prenylated natural product with good enantio- and diastereocontrol. The direct, single-step prenylation protocol developed in this work paves the way for streamlined syntheses of the prenylated natural products.

ABSTRACT A mild, efficient, and sustainable photoredox method has been developed for the synthesis of β‐aminosulfides and β‐aminosulfoxides. The transformation employs imines as readily available radical acceptors and organosilicon reagents as radical precursors, providing the desired products in good yields across a broad substrate scope. A one‐pot aerobic oxidation sequence was also established, enabling direct access to β‐aminosulfoxides under photocatalytic conditions with oxygen as the terminal oxidant. Mechanistic studies, including cyclic voltammetry, luminescence quenching, and radical inhibition experiments, revealed that α‐thiomethyl radicals are generated through a single‐electron transfer (SET) process, and that both SET and energy transfer (EnT) pathways contribute to the aerobic oxidation step.

NaN3 can facilitate the bromine atom transfer radical cyclization (ATRC) of N-allyl-2-bromoamides under visible light irradiation. The beneficial effect of NaN3 is attributable to the activating interaction between the azide anion and the C-Br bond in N-allyl-2-bromoamides. The reaction provides a metal-free approach toward γ-lactams.

Polycyclic scaffolds are central to numerous natural products and pharmaceuticals, motivating concise, stereocontrolled routes to their construction. We report a photoredox-enabled synthesis of trans-fused [n.3.0] bicyclic ketones (n = 4, 5, 10) from malonate-derived enol ethers. α-Brominated intermediates, formed by acylation with 2-bromo-2-methylpropanoyl bromide, undergo radical cyclization under two complementary conditions: (i) acridinium orange (AOH+) with Hantzsch ester (HE) at 455 nm, or (ii) photoexcited HE alone at 365 nm. Both modes trigger 6-endo-trig Giese addition, C-O bond fragmentation, and hydrogen-atom transfer to α-branched cyclic ketones that ring-close under mild Brønsted or Lewis acid activation to trans-fused products with exclusive junction control. Mechanistic studies (Stern-Volmer, UV-Vis, electrochemistry) support two activation pathways-AOH+* quenching by HE or direct HE excitation-each generating the same radical intermediates in fine. DFT calculations validate mechanistic pathways and regioselectivity in favor of philicity matching of the electrophilic radical and the polar electron-rich enol ether. The method accommodates ring-size diversity, accesses trans-hydrindanone architectures, and outcompetes 5-exo-trig spirocyclization.

A hypervalent iodine( iii ) reagent-assisted imidate radical cyclization strategy for the synthesis of diverse N -heterocycles has been developed.

We report copper-catalyzed dichloroalkyl-arylation of terminal alkenes containing a pendant aryl group bearing trichloroalkyl compounds as radical precursors. Tandem radical cyclization proceeded with high regioselectivity, short reaction times, and tolerance for a broad array of functional groups and complex substrates, yielding fused azaheterocycles such as pyrrolizidines and indolizidines, which serve as important intermediates in total synthesis. This reaction sequence affords the installation of the gem-dichloroalkyl group, a potent pharmacophore and versatile building block in organic synthesis.

The development of efficient methods for the construction of medium-sized carbocycles is extremely important in organic synthesis since many pharmaceutical agents contain these frameworks. Herein, we report an efficient strategy for the synthesis of seven- and eight-membered carbocycles via the intramolecular radical cyclization of 1,8- and 1,9-enynes. The reaction is proposed to proceed through a short-lived excited species derived from a copper acetylide complex, which engages the tethered π-system to generate a reactive intermediate capable of cyclization. The synthetic utility of this method is demonstrated through derivatizations leading to structurally diverse polycyclic compounds. This transformation offers a pratical approach to access strained medium-ring system under mild, visible-light-mediated conditions.

Herein, a novel photocatalytic ring expansion reaction of aziridines to δ‐sultams through intramolecular radical cyclization is reported. In particular, versatile N‐sulfonyl‐protected α‐ketoaziridines were envisioned to undergo a ring opening–expansion through a photoredox‐mediated radical–polar crossover (RPC) process to provide six‐membered sultams bearing an unprecedented 2,3‐disubstitution pattern. The generality of the reaction was explored with a wide variety of substrates, showing a good functional group tolerance. Moreover, the robustness of the method allows a 10‐fold upscaling, providing similar yield or diastereomeric preference for the trans‐disubstituted products. Mechanistic investigations supported the postulated radical–polar crossover pathway, involving aziridine ring opening by photocatalytic single‐electron reduction via a carbonyl radical anion, followed by intramolecular cyclization with the aryl unit of the N‐sulfonyl group and re‐aromatization. Thus, this strategy opens new possibilities for the construction of highly decorated heterocycles by photoredox‐mediated RPC ring expansion reactions.

A metal-free selective selenylation and sulfonylation of 1,7-dienes with selenosulfonates for divergent synthesis of seleno-/sulfonyl-benzoxepines has been developed. This reaction was conducted under mild conditions without any catalysts, oxidants, or additives. The choice of solvent plays a crucial role in determining the formation of seleno-/sulfonyl-benzoxepines. Preliminary mechanistic studies suggest that both the selenylation and sulfonylation are accomplished through a selenyl radical and a sulfonyl radical cyclization process.

The Cp2TiCl-mediated opening of epoxides in α,β-unsaturated ester-appended substrates leads to a cascading 5-exo-trig radical cyclization followed by lactonization yielding bicyclic lactone rings. Leveraging this strategic approach has become crucial in the construction of the core structure of many terpenoid natural products. In our present study, this methodology is further extended to the maleate/fumerate diester–appended substrates to give selectively only the 5-exo ring closure products with the [5,5] bicyclic lactone framework. This arranged the basis of a facile approach to attempt the synthesis of lingzhilactone B, an important Ganoderma meroterpenoid with two all-carbon quaternary chiral centers in the ring junction, from easily available starting materials. The modular strategy developed here can pave the synthetic pathways for many other natural products of this genre.

Bicyclo[1.1.0]butanes have attracted significant attention from synthetic chemists for their strain-release functionalization, enabling access to complex molecular architectures. This study demonstrates a photocatalyzed, strain-release-driven radical cyclization for efficiently synthesizing heteroarylated spirocyclobutyl oxindoles. By strategically incorporating redox-active functionalities into the substrate design, we achieve an unusual/reverse mode of reactivity in bicyclo[1.1.0]butanes (BCB). This approach enables the broad and efficient installation of diverse heterocycles onto spirocyclobutyl oxindoles under mild, operationally simple conditions, making it suitable for the late-stage functionalization of drug-like molecules.

The fungal-derived natural product curvularol (3) and its relative 8β-hydroxycurvularol (4) are a type of trichothecene with unique molecular skeletons and potential as anticancer agents. On the foundation of a known substituted cyclohexenone, 11-step stereocontrolled syntheses of compounds 3 and 4 were achieved. The adjacent quaternary stereocenters and crowded C5-C6 bonds in these compounds thwarted several seemingly promising strategies for synthesis. Ultimately, the combination of an intramolecular Darzens glycidic ester condensation with a stereoselective lactone propargylation/OH silylation sequence and a pivotal 5-exo dig radical cyclization gave rise to a concise strategy for constructing the curvularol-type molecular framework. In the course of this undertaking, bromo diepoxide 14 emerged as an appropriate precursor to both curvularol (3) and 8β-hydroxycurvularol (4). A zinc metal-mediated reduction of the carbon-bromine bond in 14 provided a satisfactory route to 4, while Ding and Bentrude's radical debromo-deoxygenation method was needed to transform 14 into 3 and overcome the surprising reluctance of homoallylic alcohol 13 to undergo a hydroxyl-directed epoxidation.

The traditional radical tandem cyclization of 1,6-enynes with silyl radicals happens through silyl radicals first adding to the triple bond to get alkenylsilyl compounds. Herein we disclosed a different regioselective silyl radical cyclization with 1,6-enynes to access alkenyl and silyl difunctionalized (E)-γ-lactams. Notably, the previous radical synthesis methods for γ-lactams are mostly of (Z)-configuration. This method can readily provide a series of (E)-γ-lactam derivatives through the radical cascade cyclization of the in situ generated silyl radicals with 1,6-enynes. Furthermore, this metal-free strategy proceeds under mild reaction conditions, exhibits excellent regioselectivity and stereoselectivity and 100% atom economy, as well as enables the efficient construction of Csp3-Si bonds.

We report the visible-light-induced trifluoromethylative cyclization of alkenoic thioesters, enabling the synthesis of CF3-substituted sulfur heterocycles without metals. Organophotocatalysts promote efficient radical cyclization with a broad substrate scope and high diastereoselectivity. Mechanistic studies indicate an oxidative quenching pathway initiated by photocatalyst-reagent interactions, and theoretical calculations reveal that the conformational bias of the carbocation intermediate governs the stereoselectivity. This strategy for synthesizing fluorinated sulfur heterocycles expands the synthetic utility of alkenyl thioesters in photoredox catalysis.

A transition-metal-free radical annulation strategy enabled by halogen atom transfer (XAT) has been developed for the direct construction of phenanthrene-derived polycyclic aromatic hydrocarbons (PAHs) from 2-iodobiaryls and terminal alkynes. This visible-light-mediated protocol proceeds under mild conditions and exhibits broad substrate scope, high regioselectivity, and excellent functional group tolerance. Importantly, the method can be applied iteratively to achieve homologative aromatic extension, allowing efficient access to structurally diverse and complex PAHs in just a few steps. Mechanistic studies support a radical pathway involving α-aminoalkyl radical-mediated XAT, vinyl radical cyclization, and a quantum tunneling-enabled aromatization process. This work provides a practical and scalable approach to PAHs that circumvents the limitations of conventional transition metal catalysis.

An efficient access to 6‐( γ ‐ketoalkylsulfonyl)methyl phenanthridines and 6‐(arylsulfonyl)methyl phenanthridines has been demonstrated under visible‐light photoredox‐catalyzed conditions. Exposure of biphenyl vinyl azides to strained 3°‐cyclopropanols in the presence of Ru(bpy) 3 Cl 2 and SO 2 surrogate DABSO under blue‐LED irradiation triggers a cascade radical cyclization to provide entry to the γ ‐ketosulfones–tethered phenanthridines in moderate to good yields. On the other hand, entry to the 6‐(arylsulfonyl)methyl phenanthridines is demonstrated via a complementary cascade radical cyclization event involving biphenyl vinyl azides and thianthrenium salts in the presence of Na 2 S 2 O 5 and fac ‐Ir(ppy) 3 catalyst under blue‐LED irradiation. The efficiency of the developed reactions has been established through broad substrate‐scope studies, and the mechanistic proposal is backed by incisive mechanistic probing studies.