The stereodivergent coupling via photoredox/transition metal catalysis has emerged as a powerful tool to construct diverse alkenes in both E and Z configurations. Despite well-established catalytic systems involving late transition metals, the early transition metal catalyzed stereodivergent synthesis of alkenes still remains underdeveloped. Herein in this work, a stereodivergent reductive C(sp2)-C(sp3) coupling between cycloketone oximes and vinyl halides has been achieved by tunable photoredox/Ti dual catalysis, providing a facile access to a broad scope of cyano-substituted (fluoro)alkenes with high efficiency and controlled E/Z selectivity. Several products exhibited promising antifungal activities.

Hydroalkylation of alkynes serves as a pivotal strategy for the construction of polysubstituted alkenes. However, its reaction efficiency, substrate scope, and regioselectivity are highly dependent on the structures and reactivities of both the alkynylation reagent and the hydrogen-transfer reagent. This dependence leads to common bottlenecks such as poor structural tunability, low atom economy, and side reactions often caused by the hydrogen-transfer reagent. Herein, we develop a method that combines hydroalkylation of alkynes with decarboxylative ring-opening of cyclic carboxylic acids, where the cyclic carboxylic acid simultaneously serves as the alkynylation reagent and the proton donor. By tuning the substituents and ring size of the cyclic carboxylic acid, diverse substituents can be introduced into the products. In this transformation, the cyclic carboxylic acid undergoes decarboxylative ring-opening via the ligand-to-metal charge transfer (LMCT) process to generate a long-chain alkyl radical, which subsequently adds to an alkyne to give an alkenyl radical. The alkenyl radical is then reduced to an alkenyl anion by Ce(III), and final protonation delivers polysubstituted alkenes. Through cyclic voltammetry, UV-vis absorption spectroscopy, radical trapping, intermediate conversion, and H/D exchange experiments, we demonstrate the involvement of the LMCT process and that the carboxylic acid acts as the sole proton donor.

Single-atom exchange skeleton editing serves as a central strategy for molecular reconstruction, yet achieving precise control over ring opening and atom substitution remains a significant challenge. Herein, we present a novel cobalt/photoredox dual catalytic system that enables O to N atom transmutation skeleton editing. The transformation commences with the in situ condensation of furanones and anilines to form enamine intermediates. A desaturation process, driven by sequential single-electron transfer (SET) and hydrogen atom transfer (HAT), then forges the critical O-β-aminated furan intermediates. Subsequently, under the promotion of Sc(OTf)3, nucleophilic addition and ring opening of anilines to the furan-derived intermediates occur, followed by proton transfer tautomerization and intramolecular cyclization and oxidation to afford α,β-unsaturated γ-lactams. This method precisely orchestrates a one-pot sequential O-heterocycle ring opening, O to N atom transmutation, and skeletal reorganization, enabling modular access to otherwise challenging α,β-unsaturated γ-lactams. Furthermore, the reaction operates under mild conditions with commercially available substrates. The density functional theory (DFT) calculations demonstrate that the 1,3-H shift leading to an O-β-amino-substituted furan intermediate and controllable furan nucleophilic addition-ring opening direction are pivotal to the success of this transformation.

Two-component alkene coupling reactions serve as an efficient platform for the synthesis of complex molecular architectures. Leveraging the differences in activation energy barriers among carbon radical precursors and the polarity matching between radicals, this work reports the first example of radical 1,4-acylcyanoalkylation to synthesize challenging-to-access zeta-ketonitriles using two identical alkenes. In the metal-free system, 2-(tert-butylperoxy)-2-methylpropane (DTBP) respectively activates alpha-C-H bonds of aldehydes and alkyl nitriles to generate acyl and cyanoalkyl radicals. The reaction sequence involves selective radical addition of the acyl radical to two identical alkenes, followed by radical-radical coupling with the cyanoalkyl radical, thereby constructing three C-C bonds under simple conditions. Remarkably, when tertiary alkyl aldehydes are employed, decarbonylation preferentially occurs to form alkyl radicals, enabling 1,4-alkylcyanoalkylation of alkenes. Mechanistic studies and density functional theory (DFT) calculations reveal that the success of this 1,4-acylcyanoalkylation process is governed by both the preferential addition of acyl radicals to alkenes and the thermodynamic stability associated with the two-component alkene addition cascade.

Radical-mediated trifunctionalization of alkenes, by enabling the rapid introduction of multiple functional groups, has emerged as one of the most effective strategies for the construction of functionally diverse and structurally complex molecules. Herein, we present a novel potassium peroxomonosulfate (Oxone)-mediated 1,2-ester migration strategy for the radical trifunctionalization of allyl carboxylates. This is the first case of achieving 1,3-hydroxyselenation or 1,3-hydroxysulfurization of allyl carboxylates via 1,2-ester migration, and Oxone served as both the oxidant and the hydroxyl source. The reaction efficiently constructs a C-Se/S bond and two C-O bonds in one step. Furthermore, combined experimental and density functional theory (DFT) calculations elucidate the reaction mechanism, revealing that the 1,2-ester migration can be realized through dual pathways, the three-membered (with an activation energy of 13.7 kcal/mol) and five-membered (with an activation energy of 14.6 kcal/mol) ring transition states.

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.

Herein, we report a three-component radical cascade cyclization reaction for the synthesis of iodo- and nitro-di-functionalized 4-enyl-2-pyrrolidones with 1,6-enynes under metal-free and catalyst-free conditions. In this reaction, the (Z) configuration products with high stereoselectivity are obtained. Meanwhile, this strategy is useful for the synthesis of di-functionalized lactams, and heterocyclic products have huge potential biological activities. The control experiments indicate that the cascade cyclization is realized by radical reactions, as well as the detailed reaction mechanism and regioselectivities have been explained by DFT studies.

Pyridine and its derivatives are commonly present in natural products and drug molecules. However, the synthesis of meta-functionalized pyridines has always been a challenge in the field of organic synthesis due to the regioselectivity of C-H bond activation. Here, we developed an efficient strategy for synthesizing meta-sulfonyl functionalized poly-substituted pyridine compounds via a cascade cyclization process involving 1,5-enynes bearing a chalcone skeleton and a sulfonyl radical generated by tert-butyl hydroperoxide (TBHP). This strategy can avoid the extremely difficult and challenging regioselective meta-CH bond activation of pyridines. Meanwhile, this method facilitates the one-step synthesis of various 3-sulfonyl-functionalized pyridines under metal-free and mild reaction conditions. Furthermore, the representative product 3i could be transformed into a new type of bidentate sulfur ligand, which has enormous potential for application in transition metal-catalyzed reactions. Mechanistic investigations suggest that the reaction proceeds via a free-radical pathway.

An efficient synthetic method for the nitro‐containing isoquinoline‐1,3‐diones has been achieved with tert‐butyl nitrite. This reaction features metal‐free, safety, simple operation and mild reaction conditions, which represents the first example of using stable and safe tert‐butyl nitrite as the nitro precursor for the synthesis of nitro‐containing isoquinoline‐1,3‐diones. Furthermore, both the control experiments and density functional theory calculations (DFT) have confirmed that the reaction was occurred through the radical reactions. In addition, the representative compounds 3a and 3i displayed potential good inhibitory activities for the plant height of rape and the compound 3a displayed potential promotion activity of the root length for barnyard grass.

A series of 3-phosphonyl polysubstituted pyridine were first synthesized by photocatalysis, combining a phosphonyl radical cascade reaction, Boc deprotection, and aromatization. This strategy can avoid the difficulties of activating the C3-H bond on pyridine to synthesize 3-phosphonylpyridine under mild conditions. Furthermore, by constructing different enynes, we can achieve the metal-free modular synthesis of 3-phosphonyl polysubstituted pyridine, which will be transferred into a new type of phosphine ligand. This is of significance for organometallic catalysis. The regioselective control and detailed reaction mechanism of the cascade reaction are explained by DFT calculations.

AbstractOrganophosphorus compounds have been widely used as achiral and chiral ligands in organic synthesis (PPh3, BINAP, dppe, Duphos, Xantphos, PPFA, Chiraphos, SEGPHOS), flame retardants, functional materials (LED, PV), as well as agrochemicals and medicines due to their broad biological activities. As the privileged versatile building blocks, 1,n‐enynes have been successfully applied in the synthesis of various functionalized cyclic compounds based on their two active unsaturated chemical bonds (C═C double and C≡C triple bonds). With the development of highly selective and efficient methods in organic chemistry, various organophosphorus cyclic compounds synthesis through radical cascade strategy has attracted considerable attention in recent years. In here, we have summarized the recent main achievements in the radical cascade reactions of 1,n‐enynes with phosphorus‐centered radicals. Furthermore, we also displayed the detailed reaction mechanisms in this review.

Despite the widespread utilizable value of 3-oxazolines, mild and efficient access to such a class of unique structures still remains, to date, a challenge. Herein, we present a [3 + 2] annulation strategy, guided by the retrosynthetic principle of [CO + CCN], that utilizes vinyl azides as the CCN module and aldehydes as the CO module. This approach enables the efficient construction of the 3-oxazoline framework with remarkable features, including operational simplicity, environmental friendliness, and high efficiency. Notably, it solely requires the addition of inexpensive and readily available N-hydroxyphthalimide (NHPI) and air oxygen to obtain the desired product. It also provides a new way to generate the hydroxyl radical, which is produced by the homolysis of peroxycarboxylic acid. In addition, control experiments, X-ray crystallographic analysis, high-resolution mass spectrometry (HRMS), and density functional theory (DFT) calculations afford evidence for the key intermediates (hydroxyl radical, carboxyl radical, imine radical, hydroxyl substituted amide derivatives), further confirming the path for realization of 3-oxazolines.

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp(2))-C(sp(2)) bond and a C(sp(3))-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable sigma-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the sigma-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

Cyclic compounds are widely present in natural products, pharmaceuticals, agrichemicals and materials. The development of novel, high efficient and high selective strategies for the synthesis of cyclic compounds has obtained great research interests in organic synthetic field. In past two decades, the free-radical chemistry has been greatly developed than other periods in history, in which the radical cascade cyclizations of 1,n-enynes with trifluoromethyl have emerged as a powerful strategy for the preparation of trifluoromethyl containing carbocycles and heterocycles. In this context, we review the recent advances in the radical cascade cyclization of 1,n-enynes with trifluoromethyl. Furthermore, the detailed reaction mechanisms have also been discussed.

Simple, commercially available iodine was successfully employed as a highly efficient and chemoselective catalyst for the oxidative annulation of β,γ-unsaturated hydrazones to produce 1,6-dihydropyridazines under mild conditions for the first time. Interestingly, when active β,γ-unsaturated hydrazone compounds containing electron-donating groups, such as furyl, thienyl, and cycloalkyl, were used, pyrroles were obtained. A gram-scale preparation experiment and further derivatization of pyridazines demonstrated the potential applicability of our synthesis method. Experimental studies and density functional theory calculations unveiled the origin of the chemoselectivity determining the formation of different products.

Cyclic compounds are widely present in natural products, pharmaceuticals, agrichemicals and materials. The development of novel, high atom/step-economy protocols for the synthesis of various cyclic compounds has attracted much interest in organic synthetic filed. In past two decades, the free radical reactions have been studied extremely, in which the free radical cascade annulations of 1,n-enynes with sulfur/sulfonyl radicals have suggested that this method can be used as a powerful strategy for the construction of various sulfur-containing cyclic compounds. This review summarized the recent advances in the field of radical cascade annulation of 1,n-enynes with sulfur/sulfonyl radicals. Furthermore, we also analyzed the detailed reaction mechanisms and the regioselectivities of 1,n-enynes.

We describe a novel 1,2,2-trifunctionalization of maleimides with 1,7-enynes and oxime esters through simultaneous construction of four C−C bonds and a C≡N bond in one pot based on the radical relay/1,5-hydrogen-atom transfer (HAT).

The construction of all-carbon quaternary centers, especially those containing an alkyne-substituted framework, represents an important challenge in organic synthesis. Here we present a novel Fe-catalyzed selective formal insertion of diazo compounds into C(sp)-C(sp(3)) bonds of propargyl alcohols under mild conditions that enables the streamlined construction of alkyne-substituted all-carbon quaternary centers. This unique strategy starts with in situ generation of an ester group in the presence of carboxylic acids, followed by insertion of metal-carbene into C(sp)- C(sp(3)) bonds, which may open up a new reaction mode for exploring metal-carbene insertion into acyclic C-C bonds.

Formal intramolecular 1,3-OH migration of α-imino carbene was achieved producing a unique zwitterion, and the subsequent selective annulation afforded α-amino cyclobutanone. Features such as readily available substrates, mild reaction conditions, a time-saving procedure, excellent functional group compatibility, and valuable transformations of the products qualified this unique protocol as an efficient tool for the synthesis of strained cyclic compounds. Density functional theory calculations were in good agreement with experimental observations, and a plausible mechanism is presented.

Herein, an unprecedented non-noble-metal-catalyzed oxidation/cyclization of ene-ynamides is developed, allowing the synthesis of diversely functionalized lactams in moderate to good yields with excellent diastereoselectivities without the observation of typical cyclopropanation products. In combination with Ellman's tert-butylsulfinimine chemistry, chiral γ-lactams containing three contiguous stereocenters are obtained with high diastereo- and enantioselectivity. Moreover, density functional theory (DFT) calculations indicate that this protocol probably undergoes a carbon cation or proton transfer process.