Photoredox Site-Selective C(sp)-H Alkylation of 1-(-Iodoaryl)-alkan-1-ones with Activated Alkenes Enabled by Hydrogen Atom Transfer.

A visible-light-mediated photoredox catalysis for β-C(sp)-H alkylation of 1-(-iodoaryl)alkan-1-ones with alkenes via 1,5-hydrogen atom transfer and alkene alkylarylation to produce diverse β-alkyl arylalkanones containing a quaternary carbon center is presented. This method is applicable to a wide range of 1-(-iodoaryl)alkan-1-ones and activated alkenes. Mechanistic studies suggest that the reaction involves a radical process.

Photocatalytically switchable chemoselective difluoramidation of olefins for the synthesis of diversified difluoro-γ-lactams.

Herein, we describe a visible light-promoted intramolecular difluoramidation reaction of olefins. By precisely adjusting the reaction conditions, the difficult-to-control olefin radical addition process was effectively controlled. Heck-type coupling of olefins and hydrofluoroamidation of olefins, as well as difunctionalization of olefins, were successfully achieved with good selectivity.

Palladium/Norbornene Cooperative Catalysis 2-Fold C-H/C-X Coupling: Construction of Polycyclic Aromatic Hydrocarbons from Brominated Benzimidazoles.

A palladium/norbornene (NBE)-catalyzed 2-fold C-H/C-X coupling reaction of aryl iodides is reported. Bromine-substituted benzimidazoles were chosen as electrophilic and termination reagents, and the versatile polycyclic aromatic hydrocarbon products were successfully obtained. The strategy overcomes the challenge of catalyst poisoning by heterocyclic substrates.

Electrochemical 1,2-Alkylarylation of Styrenes with Malonates and -Heteroarenes via Direct C(sp)-H/C(sp)-H Functionalization.

A general and atom-economical electrochemical dehydrogenative method for the intermolecular 1,2-alkylarylation of styrenes with malonates and nucleophilic -heteroarenes (including indoles and pyrroles) has been developed. This transformation provides a regioselective route to construct highly valuable 1,1-diarylalkanes enabled by C(sp)-H/C(sp)-H functionalization under mild conditions, and H is the only theoretical byproduct. Mechanistic studies indicated that the reaction proceeded through the oxidative of the C(sp)-H bond to generate alkyl radical, radical addition across the C═C bond, single electron oxidation and C(sp)-H functionalization cascades.

Palladium-Catalyzed Dearomative -/-Cycloaddition Cascades of -Allylanilines with 1,4-Enynes and CO via Skeletal Reorganization.

A selectivity-control approach for palladium-catalyzed dearomative -/-cycloaddition cascades of aromatic compounds with 1,4-enynes and CO via a skeletal reorganization process to produce polycycle-fused bicyclo[2.2.2]octenes is reported.

Electrochemical Difunctionalization of Alkenes.

Owing to their wide utilizations in synthesis and their products prevalence in numerous natural products, pharmaceuticals and functional materials, the alkene difunctionalization methods for the selective transformations of the olefins are important and have attracted much attention form the synthetic chemists. Among them, the electrochemical alkene difunctionalization reaction is particularly promising and has becoming a potent and sustainable tool for the selective transformations of alkenes into vicinal difunctionalized structures in organic synthesis through simultaneous incorporation of two functional groups. Herein, we summarize recent progress in the electrochemical alkene difunctionalization reactions according to the alkene difunctionalization types as well as the category of the radicals over the past five years.

Divergent Synthesis of ()- and ()-Alkenones via Photoredox C(sp)-H Alkenylation-Dehydrogenation of -Iodoarylalkanols with Alkynes.

A photoredox C(sp)-H alkenylation-dehydrogenation of -iodoarylalkanols with terminal alkynes for the synthesis of ()- and ()-quaternary carbon center-containing pent-4-en-1-ones is described. The stereoselectivity depends on the utilization of alkynes and photocatalysts. While using an organic photocatalyst like 4-DPAIPN manipulates the C(sp)-H alkenylation-dehydrogenation of -iodoarylalkanols with arylalkynes to assemble ()-pent-4-en-1-ones, in the case of an Ir potocatalyst such as Ir(ppy)(dtbbpy)PF the reaction with arylalkynes delivers ()-pent-4-en-1-ones.

[Chen Zhiqian's Thoughts on Public Health in the 1920s].

During his studies at the Peking Union Medical College (1921-1929),Chen Zhiqian formed his thoughts on public health under the influences of modern medical education and the advanced thinking of the times,which laid an ideological foundation for his later engagement in rural health care and reflected the medical progress in China at that time.In the 1920s,Chen Zhiqian's thoughts on public health mainly encompassed five aspects.First,health was a cornerstone of the country's wealth and people's well-being.

Synthesis of Diarylalkanes by Photoreductive 1,2-Diarylation of Alkenes with Aryl Halides and Cyanoaromatics.

We report a visible light-induced photoreductive strategy for three-component diarylation of alkenes with aryl halides and cyanoaromatics. Upon photoredox catalysis and with tertiary alkyl amines as the electron transfer agent, aryl halides selectively undergo halogen atom transfer to generate the aryl radicals and two C(sp)-C(sp) bonds between the cabron atoms are created in a radical addition and radical-radical coupling fashion to rapidly assemble diverse functionalized polyarylalkanes with high regio- and chemoselectivity. This method can be applied to broad feedstocks, including terminal alkenes, internal alkenes, aryl iodides, aryl bromides, aryl chlorides, electron-deficient benzonitriles, and isonicotinonitriles.

Photoreductive 1,4-Dicarbofunctionalization of 1,3-Enynes with Organoiodides and Cyanoarenes via Halogen-Atom Transfer.

A photoreductive halogen-atom transfer (XAT) strategy for 1,4-dicarbofunctionalization of 1,3-enynes with organoiodides and cyanoarenes is disclosed, enabling access to functionalized allenes in a highly regio-, chemo-, and stereoselective manner. Upon the photoredox catalysis and the activation of EtN XAT agents, the mild conditions and high functional group tolerance of this protocol enable the formation of two C-C bonds, including a C(sp)-C(sp) bond and a C(sp)-C(sp) bond, in a single reaction step, and provides a general avenue to polysubstituted allenes and late-stage modification of bioactive compounds.

Electrochemical Dehydrogenative [3 + 2]/[5 + 2] Annulation of -Arylacrylamides with γ,σ-Unsaturated Malonates via Direct C(sp)-H/C(sp)-H Functionalization.

Herein, we introduce an electrochemical dehydrogenative [3 + 2]/[5 + 2] annulation of easily available -arylacrylamides with γ,σ-unsaturated malonates through C(sp)-H/C(sp)-H functionalization. The employment of inexpensive ferrocene as the redox catalyst allows access to diverse benzo[]azepin-2-ones in moderate to excellent yields without stoichiometric oxidants. This protocol features broad substrate scope and excellent selectivity, and mechanistic studies indicated that the reaction proceeded through the oxidation of a C(sp)-H bond to generate an alkyl radical, radical addition across the C═C bond, [3 + 2]/[5 + 2] annulations, and C(sp)-H functionalization cascades.

Photo-/Electrocatalytic Difunctionalization of Alkenes Enabled by C-H Radical Functionalization.

The difunctionalization of alkenes represents a powerful tool to incorporate two functional groups into the alkene bones for increasing molecular complexity and has been widely utilizations in chemical synthesis. Upon the catalysis of the green, sustainable, mild photo-/electrochemistry technologies, much attentions have been attracted to the development of new tactics for the transformations of the important alkene and alkane feedstocks driven by C-H radical functionalization. Herein, we summarize recent advances in the photo-/electrocatalytic difunctionalization of alkenes enabled by C-H radical functionalization.

Ru(II)-Catalyzed C-H Amination of 1,2,3-Benzotriazinones with Azide Compounds.

A Ru(II)-catalyzed directed C-H amination of 1,2,3-benzotriazinones with azide compounds has been reported. The reaction has a wide substrate scope of organic azides with good results and represents a useful pathway to the construction of versatile heterocyclic amino products. In addition, the method can be used for the phthalazinones, highlighting the synthetic practicability of the strategy.

Theoretical Insights into the Mechanism and Origin of Solvent-Dependent Selectivity in the Cyclization of Propargyl Alcohols for the Divergent Synthesis of N-Heterocycles.

This study elucidates the mechanisms and principles governing chemoselectivity in synthesizing two distinct N-heterocycles, benzimidazole thiazine and benzothiazole imidazole, through BF•OEt-catalyzed cyclization reactions of propargyl alcohols with benzimidazole thiols. Employing density functional theory calculations, we highlight the crucial role of fluorine source in influencing chemoselectivity. In DCM, BF, as the catalytic center, coordinates with propargyl alcohol's hydroxyl group to form a precursor.

Photochemical Divergent Ring-Closing Metathesis of 1,7-Enynes: Efficient Synthesis of Spirocyclic Quinolin-2-ones.

A photocatalytic method for the ring-closing 1,7-enyne metathesis using the α-amino radical as an alkene deconstruction auxiliary is present. Preliminary mechanistic studies suggest that intramolecular 1,5-hydrogen atom transfer is the key to the generation and β-scission of the α-amino radical, while the dearomatization of arenes and ring opening of cyclopropanes are the key to construct spirocyclic quinolin-2-ones. This approach highlights the potential of ring-closing 1,7-enyne metathesis, providing a green, efficient, and step-economical way for the synthesis of spirocyclic quinolin-2-ones.

Photoredox Ring Opening 1,2-Alkylarylation of Alkenes with Sulfonium Salts Toward Thioether-Substituted Oxindoles.

A novel strategy for the difunctionalization of electron-deficient alkenes with aryl sulfonium salts to access remote sulfur-containing oxindole derivatives by using in situ-formed copper(I)-based complexes as a photoredox catalyst is presented. This method enables the generation of the C(sp)-centered radicals through site selective cleavage of the C-S bond of aryl sulfonium salts under mild conditions. Moreover, the oxidation reactions of desired products provide a new strategy for the preparation of sulfoxide or sulfone-containing compounds.

Iodoarene-directed photoredox β-C(sp)-H arylation of 1-(-iodoaryl)alkan-1-ones with cyanoarenes halogen atom transfer and hydrogen atom transfer.

Site selective functionalization of inert remote C(sp)-H bonds to increase molecular complexity offers vital potential for chemical synthesis and new drug development, thus it has been attracting ongoing research interest. In particular, typical β-C(sp)-H arylation methods using chelation-assisted metal catalysis or metal-catalyzed oxidative/photochemical generated allyl C(sp)-H bond processes have been well developed. However, radical-mediated direct β-C(sp)-H arylation of carbonyls remains elusive.

Electroreductive Remote Benzylic C(sp)-H Arylation of Aliphatic Ethers Using Cyanoarenes for the Synthesis of α-(Hetero)aryl Ethers.

An iodoarene-driven electroreductive remote C(sp)-H arylation of unsymmetrical 1-(-iodoaryl)alkyl ethers with cyanoarenes for the site selective synthesis of α-(hetero)aryl ethers is developed. With the introduction of cyanoarenes as both aryl sources and electron transfer mediators, this method includes an iodoarene-driven strategy to enable the regiocontrollable formation of two new bonds, one C(sp)-H bond, and one C(sp)-C(sp) bond, in a single reaction step through the sequence of halogen atom transfer (XAT), hydrogen atom transfer (HAT), radical-radical coupling, and decyanation.

Photoredox-Catalyzed Alkylarylation of -Aryl Bicyclobutyl Amides with α-Carbonyl Alkyl Bromides: Access to 3-Spirocyclobutyl Oxindoles.

A visible-light-induced radical alkylarylation of -aryl bicyclobutyl amides with α-carbonyl alkyl bromides for the synthesis of functionalized 3-spirocyclobutyl oxindoles is described in which β-selective radical addition of the alkyl radical to -aryl bicyclobutyl amides forms a key radical intermediate followed by interception with intrinsic arene functional group. This approach can be applicable to a wide range of α-carbonyl alkyl bromides, including primary, secondary, and tertiary α-bromoalkyl esters, ketones, nitriles, and nitro compounds.

Cobalt-Promoted Photoredox 1,2-Amidoamination of Alkenes with -Sulfonamidopyridin-1-ium Salts and Free Amines.

A cobalt-promoted photoredox 1,2-amidoamination of alkenes with -sulfonamidopyridin-1-ium salts and free amines for the synthesis of unsymmetrical vicinal diamines has been developed. The reaction handles -(sulfonamido)pyridin-1-ium salts as the sulfonamidyl radical precursors and free amines as the nucleophilic terminating reagents to enable the formation of two new C(sp)-N bonds in a single reaction step and offers a route to selectively producing unsymmetrical vicinal diamines with an exquisite selectivity and a good compatibility of functional groups.

Nickel-Catalyzed Reductive Cross-Coupling of Propargylic Acetates with Chloro(vinyl)silanes: Access to Silylallenes.

Because of their various reactivities, propargyl acetates are refined chemical intermediates that are extensively applied in pharmaceutical synthesis. Currently, reactions between propargyl acetates and chlorosilanes may be the most effective method for synthesizing silylallenes. Nevertheless, owing to the adaptability and selectivity of substrates, transition metal catalysis is difficult to achieve.

Divergent [2 + ] Heteroannulation of β-CF-1,3-enynes with Alkyl Azides via Hydrogen Atom Transfer and Radical Substitution.

A copper-promoted divergent intermolecular [2 + ] heteroannulation of β-CF-1,3-enynes with alkyl azides via alkyl radical-driven HAT and radical substitution (C-C bond formation) to form four- to ten-membered saturated -heterocycles is developed. This method enables the aryl-induced or kinetically controlled site selective functionalization of the remote C(sp)-H bonds at positions 2, 3, 4, 5, 6, 7, or 8 toward the nitrogen atom through triplet nitrene formation, radical addition across the C═C bond, HAT and radical substitution cascades, and features a broad substrate scope, excellent site selectivity, and facile late-stage derivatization of bioactive molecules. Initial deuterium-labeling and control experiments shed light on the reaction mechanism via nitrene formation and HAT.

Palladium/Norbornene Cooperative Catalysis Bifunctionalization: Acylation/Cyanation of Aryl Iodides by Cleaving C-CN Bond of Aryl Acyl Nitrile.

A palladium/norbornene catalyzed two-component coupling process involving acylation/cyanation of aryl iodides is reported. In this work, aryl acyl nitrile compounds are cleverly selected to provide both nitrile and acyl sources by palladium-catalyzed cleavage of the C-CN bond as both an electrophilic reagent and a termination reagent. This is the first example of C-CN bond cleavage bifunctionalization of aryl iodides.

Aryldiazonium-Salt-Triggered Carboxylative Azotization of Pyrroles or Indoles with Polyhalomethanes via Halogen-Atom Transfer (XAT).

A halogen-atom-transfer (XAT)-based method for carbonylazotization of pyrroles or indoles with aryldiazonium salts and polyhalomethanes via dual C(sp)-H bond functionalization is described. Using aryldiazonium salts realizes carbonylation/azotization of pyrroles or indoles via polyhalomethyl-radical-mediated and electrophilic substitution, thus providing a green, efficient, and step-economy approach for synthesis of multifunctional pyrroles or indoles from the easily available substrates. Notably, this strategy relies on the use of aryldiazonium salts to extend the well-established iodine atom transfer to bromine or chlorine atom transfer.