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The modulation of selectivity of highly reactive carbon radical cross-coupling for the construction of C-C bonds represents a challenging task in organic chemistry. N-Heterocyclic carbene (NHC) catalyzed radical transformations have opened a new avenue for acyl radical cross-coupling chemistry. With this method, highly selective cross-coupling of an acyl radical with an alkyl radical for efficient construction of C-C bonds was successfully realized. However, the cross-coupling reaction of acyl radicals with vinyl radicals has been much less investigated. We herein describe NHC and visible light-mediated photoredox co-catalyzed radical 1,4-sulfonylacylation of 1,3-enynes, providing structurally diversified valuable tetrasubstituted allenyl ketones. Mechanistic studies indicated that ketyl radicals are formed from aroyl fluorides

1,3,5-tri-substituted benzene rings emerged with unique properties has widespread applications in materials, boosting the rapid development of their synthesis. Despite the significance, the direct construction of hetero-1,3,5-trisubstituted benzene core was far less-developed. Herein, we realized a DBU-mediated isomerization/6-π electro-cyclization/oxidative aromatization cascade of sulfonyl-substituted allenyl ketones under an air atmosphere. This versatile protocol featured metal-free conditions, easy operation, and broad functional group tolerance provides a new avenue for the construction of hetero-1,3,5-tri-substituted benzene.

Reported herein is the atroposelective synthesis of biaryl NH isoquinolones by RhIII -catalyzed C-H activation of benzamides and intermolecular [4+2] annulation for a broad scope of 2-substituted 1-alkynylnaphthalenes, as well as sterically hindered, symmetric diarylacetylenes. The axial chirality is constructed based on dynamic kinetic transformation of the alkyne in redox-neutral annulation with benzamides, with alkyne insertion being stereodetermining. The reaction accommodates both benzamides and heteroaryl carboxamides and proceeds in excellent regioselectivity (if applicable) and enantioselectivities (average 91.8 % ee). An enantiomerically and diastereomerically pure rhodacyclic complex was prepared and offers insight into enantiomeric control of the coupling system, wherein the steric interactions between the amide directing group and the alkyne substrate dictate both the regio- and enantioselectivity.

Axially chiral aldehydes have received increasing attention in enantioselective catalysis. However, only very few catalytic methods have been developed to construct structurally diverse axially chiral aldehydes. We herein describe an NHC-catalyzed atroposelective esterification of biaryl dialdehydes as a general and practical strategy for the construction of axially chiral aldehydes. Mechanistic studies indicate that coupling proceeds through a novel combination of NHC-catalyzed desymmetrization of the dialdehydes and kinetic resolution. This protocol features excellent enantioselectivity, mild conditions, good functional-group tolerance, and applicability to late-stage functionalization and provides a modular platform for the synthesis of axially chiral aldehydes and their derivatives.

Rh(iii)-catalyzed synthesis of vicinal diamides has been realized via elaboration of an authenticated Rh-C(sp3) species generated via initial intramolecular amidorhodation of olefins. The second amidation was achieved using both electrophilic and nucleophilic amidating reagents. The reactions proceeded under mild conditions with good yield, broad substrate scope, and excellent functional-group tolerance.

Enantiomeric access to pentatomic biaryls is challenging due to their relatively low rotational barrier. Reported herein is the mild and highly enantioselective synthesis of 2,3'-biindolyls via underexplored integration of C-H activation and alkyne cyclization using a unified chiral Rh(III) catalyst. The reaction proceeded via initial C-H activation followed by alkyne cyclization. A chiral rhodacyclic intermediate has been isolated from stoichiometric C-H activation, which offers direct mechanistic insight.

Pyridines/pyrimidines are common and effective directing groups in C-H activation. However, they are poorly functionalizable heteroarenes. Reported in this work is Mn-catalyzed dehydrocyanative transannulation between three classes of heteroarenes and propargyl carbonates. The pyridyl/pyrimidyl groups in the heteroarenes initially function as directing groups to enable C-H allenylation; they then undergo intramolecular Diels-Alder/retro-Diels-Alder reactions with the allene moiety to afford fused carbo/heterocycles. Three key intermediates at different stages of the reaction were isolated.

Nitrogen-rich heterocyclic compounds have a profound impact on human health. Despite the numerous synthetic methods, diversified, step-economic, and general synthesis of heterocycles remains limited. C-H bond functionalization catalyzed by rhodium(iii) cyclopentadienyls has proven to be a powerful strategy in the synthesis of diversified heterocycles. Herein we describe rhodium(iii)-catalyzed sp2 and sp3 C-H activation-oxidative annulations between aromatic substrates and 1,3-enynes, where alkenyl-to-allyl 1,4-rhodium(iii) migration enabled the generation of electrophilic rhodium(iii) π-allyls via remote C-H functionalization. Subsequent nucleophilic trapping of these species by various sp2-hybridized N-nucleophiles delivered three classes (external salts, inner salts, and neutral azacycles) of five-membered azacycles bearing a tetrasubstituted saturated carbon center, as a result of [4 + 1] annulation with the alkyne being a one-carbon synthon. All the reactions proceeded under relatively mild conditions with broad substrate scope, high efficiency, and excellent regioselectivity. The synthetic applications of this protocol have also been demonstrated, and experimental studies have been performed to support the proposed mechanism.

Cu-catalyzed redox-divergent [3+3] coupling of oxime esters with β-CF3 enones and acrylates is described. This redox-neutral coupling with enones and acrylates affords trifluoromethylated pyridines and pyridones, respectively. Under reductive conditions, difluoromethylated pyridines, difluoromethlated pyridones, and trifluoromethylated dihydropyridones are obtained. The reactions occur under mild conditions with broad substrate scope and regio/redox selectivity.

Cp*RhIII /IrIII complexes are known to play important roles in both C-H activation and transfer hydrogenation (TH). However, these two areas evolved separately. They have been integrated in redox- and chemodivergent coupling reactions of N-pyridylanilines with enones. The iridium-catalyzed coupling with enones leads to the efficient synthesis of tetrahydroquinolines through TH from i PrOH. Counterintuitively, i PrOH does not serve as the sole hydride source, and the major reaction pathway involves disproportionation of a dihydroquinoline intermediate, followed by the convergent and iterative reduction of quinolinium species.

Chemodivergent and redox-neutral annulations between N-methoxybenzamides and sulfoxonium ylides have been realized via Rh(III)-catalyzed C–H activation. The sulfoxonium ylide acts as a carbene precursor, and coupling occurs under acid-controlled conditions, where Zn(OTf)2 and PivOH promote chemodivergent cyclizations.

An efficient, atom-economical, and regioselective insertion of indoles into terminal alkynes has been realized via cobalt(III)-catalyzed C–H activation under mild conditions, leading to efficient synthesis of α-gem-vinylindoles. The insertion of the alkynes follows a rare 1,2-selectivity, and silyl alkynes, alkyl alkynes, propargyl alcohols, and protected propargyl amines are all applicable. The mechanism of this hydroarylation system has been studied in detail by a combination of experimental and computational approaches. In the reaction of silyl terminal alkynes, the regioselectivity is dictated by the steric effects of the alkyne substituent, especially in the protonolysis stage. However, for protected propargyl amines, the selectivity results from electronic effects during the insertion step, with protonolysis being insignificant in the determination of selectivity. An internal alkyne also coupled in high efficiency but with low regioselectivity. Comparisons of cobalt, rhodium, and iridium catalysts h...

C-H bond activation is mostly limited to ortho selectivity. Activation of both ortho and meta C-H bonds constitutes a particularly important strategy for annulation, but has rarely been studied in enantioselective systems. Reported herein is rhodium(III)-catalyzed asymmetric [3+2] transannulation of arenes with 7-azabenzonorbornadienes. Two distinct classes of arenes have been identified as substrates, and the coupling proceeded with high enantioselectivity and excellent diastereoselectivity through sequential activation of ortho and meta C-H bonds.

Mn(i)-Catalyzed synthesis of seven- or eight-membered carbocycles is disclosed via C-H activation of heteroarenes and coupling with alkyne-functionalized 1,3-cyclopentadiones or 1,3-cyclohexadiones. This n to n + 2 (n = 5, 6) ring expansion reaction proceeded via a C-H alkenylation/carbonyl addition/retro-Aldol cascade. Structurally diverse mid-sized carbocycles were constructed via cleavage of both C-H and C-C bonds in a single operation.

A facile, copper-catalyzed aminoarylation reaction of various aryl/alkyl alkynes was realized by utilizing N-fluoroarylsulfonimides (NFSI) as aminoarylation or amination reagent with hydroxyl as directing group. With this methodology, various α,β-unsaturated carbonyl compounds and indenones were efficiently constructed, and the synthetic application for indole derivatives was also provided. The aminoarylation reactions operate via a regiospecific addition of copper-coordinated nitrogen radical to C–C triple bond/Cvinyl–Caryl bond formation followed by other series of radical processes.

Chiral rhodium(III) cyclopentadienyl catalysts (CpX RhIII ) play significant roles in asymmetric arene C-H activation. Rh/Ir-catalyzed couplings of arenes and strained rings have been well-studied, but they have been limited to racemic systems. Reported in this work is the Cpx RhIII /AgSbF6 -catalyzed enantioselective desymmetrizative C-C coupling of N-pyrimidylindoles and 7-azabenzonorbornadienes with high efficiency and enantioselectivity. The role of AgSbF6 has been established by mechanistic studies. AgSbF6 enhances the catalytic activity by suppressing the C3-H activation of the indoles, activation which would otherwise lead to catalytically inactive species.

Antibiotics are of concern due to their prevalent detection in aquatic environment. Sulfate radical based advanced oxidation processes show a great capacity to degrade antibiotics, but the mechanisms are still unclear. In this work, the degradation mechanism of fluoroquinolones (FQs), a major group of antibiotics, in UV/Fe2+/PMS was deeply investigated. The degradation process was in-situ and real-time monitoring by illumination-assisted droplet spray ionization mass spectrometry. A series of reactive intermediates were captured, and further characterized by high-resolution mass spectrometry (HRMS) and tandem MS. About 50 different transformation products have been identified for ciprofloxacin and norfloxacin. More than 15 products were the first time reported. Taking into consideration of the sequential formation and intensity change of intermediates, the feasible and complete transformation pathways of FQs were proposed. Compared with the photolysis process, the defluorination of FQs was not observed in this system. This work provided abundant information of FQs degradation by persulfate advanced oxidation processes (AOPs) and meanwhile demonstrated the importance of HRMS and on-line MS in mechanism research of AOPs.

By using N-fluorobenzenesulfonimide as both the oxidant and the amination reagent, we have realized the first example of the intermolecular chalcogenative amination of alkynes, which grants facile, highly regio- and stereoselective access to chalcogenated enamides. The reaction features mild conditions, high yields and selectivities, remarkably broad substrate scope, and excellent functional group tolerance. Mechanistic studies indicate the in situ generated chalcogen imidates to be the actual reactive species, which in turn, has clarified the mechanism of related transformations. These reactions represent significant additions to the development of the highly selective amino bisfunctionalization of alkynes.

Cascade reactions initiated by radical addition to alkynes are synthetically very attractive because they enable access to highly complex molecular skeletons in only few synthetic steps under usually mild conditions. Here we report a general radical cascade reaction of alkynes, N-fluoroarylsulfonimides and alcohols, enabling the efficient synthesis of important α-amino-α-aryl ketones from readily available starting materials via a single operation. During this process, the highly regioselective nitrogen-centred radical addition to internal and terminal alkynes generating vinyl radicals and the next explicit migration of aryl group from the nitrogen source lead the following efficient desulfonylation, oxygenation, and semi-pinacol rearrangement. In addition, the semi-pinacol rearrangement precursors, α-alkyloxyl-α,α-diaryl imines, could also be efficiently obtained under milder conditions. This methodology might open a new entry for designing intermolecular radical cascade reaction of alkynes., Cascade and multi-component reactions allow highly functionalized molecules to be built from simpler precursors. Here, the authors report a three-component coupling giving α-amino-α-aryl ketones, initiated by the regioselective addition of nitrogen radicals to alkynes.