Metal-free directed sp2-C-H borylation.

Organoboron reagents are important synthetic intermediates that have a key role in the construction of natural products, pharmaceuticals and organic materials1. The discovery of simpler, milder and more efficient approaches to organoborons can open additional routes to diverse substances2-5. Here we show a general method for the directed C-H borylation of arenes and heteroarenes without the use of metal catalysts. C7- and C4-borylated indoles are produced by a mild approach that is compatible with a broad range of functional groups. The mechanism, which is established by density functional theory calculations, involves BBr3 acting as both a reagent and a catalyst. The potential utility of this strategy is highlighted by the downstream transformation of the formed boron species into natural products and drug scaffolds.

Regioselective Deuteration of Arenes Enabled by Simple Heterogeneous Palladium Catalysis.

A heterogeneous redox-neutral palladium-catalytic platform was reported for the preparation of deuterated (hetero) arenes from (hetero) arenes mediated by regioselective C(sp2)-H thianthrenation utilizing commercially available and recyclable Pd/C catalyst. A wide range of deuterated compounds could be obtained in high yields with excellent levels of deuterium incorporation under these simple heterogeneous catalytic conditions with the requirement of stable and easily handled DCOONa as a deuterium source. The late-stage deuteration of pharmaceuticals and bioactive molecules was also achieved by this approach.

Diboron-promoted iron-catalyzed denitrative vinylation of ß-nitrostyrenes with cycloketoximes.

We have developed a new iron-catalyzed ring opening alkenylation of cycloketoximes with ß-nitrostyrenes for the facile synthesis of flexible distal cyanoalkyl alkenes. Both non-active strained cycloketoximes and less-strained cycloketoximes could be coupled with ß-nitrostyrenes with excellent regio- and stereoselectivity under base-free redox-neutral conditions. The diboron reagent played an irreplaceable role in this transformation. A reasonable radical-mediated process could be involved in this catalytic cycle.

Photoinduced Etherification of Less-Strained Cycloketoxime Esters Enabled by C-C Bond Cleavage.

We report a general, scalable, and convenient photochemical process for diversities of distal oxygenated nitriles from corresponding less-strained ketoxime esters allowing one-step introductions of ether and cyano groups, which avoids the utilization of toxic cyanide reagents. A wide range of ketoxime esters involving five-membered to eight-membered cycloketoxime esters and linear ketoxime esters participate smoothly under operately simple and mild conditions, affording structurally variable ring-opening products.

Synthesis of functionalized malononitriles via Fe-catalysed hydrogen atom transfers of alkenes.

Described herein is a practical and convenient approach that enabled radical-mediated conjugate addition of unreactive alkenes to electron-deficient alkenes leading to a broad range of substituted malononitriles. These reactions are believed to proceed by Fe-catalysed hydrogen atom transfer (HAT) onto the alkenes affording carbon-centered radical intermediates with Markovnikov selectivity, followed by the capture of electron-deficient alkenes. We explored this synthesis approach under mild conditions with high efficiency and broad substrate scope and the utility is highlighted by the further synthetic transformations of the obtained substituted malononitriles.

Metal-catalysed C-Het (F, O, S, N) and C-C bond arylation.

The formation of C-aryl bonds has been the focus of intensive research over the last decades for the construction of complex molecules from simple, readily available feedstocks. Traditionally, these strategies involve the coupling of organohalides (I, Br, Cl) with organometallic reagents (Mg, Zn, B, Si, Sn,…) such as Kumada-Corriu, Negishi, Suzuki-Miyaura, Hiyama and Sonogashira cross-couplings. More recently, alternative methods have provided access to these products by reactions with less reactive C-Het (F, O, S, N) and C-C bonds. Compared to traditional methods, the direct cleavage and arylation of these chemical bonds, the essential link in accessible feedstocks, has become increasingly important from the viewpoint of step-economy and functional-group compatibility. This comprehensive review aims to outline the development and advances of this topic, which was organized into (1) C-F bond arylation, (2) C-O bond arylation, (3) C-S bond arylation, (4) C-N bond arylation, and (5) C-C bond arylation. Substantial attention has been paid to the strategies and mechanistic investigations. We hope that this review can trigger chemists to discover more efficient methodologies to access arylation products by cleavage of these C-Het and C-C bonds.

ZnBr2-Catalyzed Dehydrogenative Borylation of Terminal Alkynes.

The simple, commercially available ZnBr2 has been successfully employed as a highly efficient and chemoselective catalyst for the dehydrogenative borylation of terminal alkynes with HBpin under mild conditions. It shows a good tolerance toward various functional groups such as aryl, alkyl, heteroaryl, etc. The plausible reaction mechanism has been investigated based on the corresponding stoichiometric experiments and DFT calculations.

SOMOphilic Alkynylation of Unreactive Alkenes Enabled by Iron-Catalyzed Hydrogen Atom Transfer.

We report an efficient and practical iron-catalyzed hydrogen atom transfer protocol for assembling acetylenic motifs into functional alkenes. Diversities of internal alkynes could be obtained from readily available alkenes and acetylenic sulfones with excellent Markovnikov selectivity. An iron hydride hydrogen atom transfer catalytic cycle was described to clarify the mechanism of this reaction.

Enabling the Use of Alkyl Thianthrenium Salts in Cross-Coupling Reactions by Copper Catalysis.

Alkyl groups are one of the most widely used groups in organic synthesis. Here, a a series of thianthrenium salts have been synthesized that act as reliable alkylation reagents and readily engage in copper-catalyzed Sonogashira reactions to build C(sp3 )-C(sp) bonds under mild photochemical conditions. Diverse alkyl thianthrenium salts, including methyl and disubstituted thianthrenium salts, are employed with great functional breadth, since sensitive Cl, Br, and I atoms, which are poorly tolerated in conventional approaches, are compatible. The generality of the developed alkyl reagents has also been demonstrated in copper-catalyzed Kumada reactions.

Single-Electron-Transfer-Induced C(sp3)-N Couplings via C-C Bond Cleavage of Cycloketoxime Esters.

A practical single-electron-transfer-induced selective C(sp3)-N coupling of cycloketoximes with anilines via C-C bond cleavage under copper-catalytic and synergetic photoredox/copper-catalytic reaction systems has been uncovered. These two powerful and simple protocols demonstrated excellent selectivity and good functional group compatibility without any base or ligand control. Preliminary mechanistic experiments indicated that a radical-mediated process was involved in these transformations.

An Olefinic 1,2-Boryl-Migration Enabled by Radical Addition: Construction of gem-Bis(boryl)alkanes.

A series of in situ formed alkenyl diboronate complexes from alkenyl Grignard reagents (commercially available or prepared from alkenyl bromides and Mg) with B2 Pin2 (bis(pinacolato)diboron) react with diverse alkyl halides by a Ru photocatalyst to give various gem-bis(boryl)alkanes. Alkyl radicals add efficiently to the alkenyl diboronate complexes, and the adduct radical anions undergo radical-polar crossover, specifically, a 1,2-boryl-anion shift from boron to the α-carbon sp2 center. This transformation shows good functional-group compatibility and can serve as a powerful synthetic tool for late-stage functionalization in complex compounds. Measurements of the quantum yield reveal that a radical-chain mechanism is operative in which the alkenyl diboronates acts as reductive quencher for the excited state of the photocatalyst.

Copper-Catalyzed Intermolecular Heck-Like Coupling of Cyclobutanone Oximes Initiated by Selective C-C Bond Cleavage.

The first example of intermolecular olefination of cyclobutanone oximes with alkenes via selective C-C bond cleavage leading to the synthesis of nitriles in the presence of a cheap copper catalyst is reported. The procedure is distinguished by mild and safe reaction conditions that avoid ligand, oxidant, base, or toxic cyanide salt. A wide scope of cyclobutanones and olefin coupling components can be used without compromising efficiency and scalability. The alternative visible-light-driven photoredox process for this coupling reaction was also uncovered.

Transition-metal-catalyzed Chelation-assisted C-H Functionalization of Aromatic Substrates.

In the past decade, transition-metal-catalyzed C-H activations have been very popular in the research field of organometallic chemistry, and have been considered as efficient and convenient strategies to afford complex natural products, functional advanced materials, fluorescent compounds, and pharmaceutical compounds. In this account, we begin with a brief introduction to the development of transition-metal-catalyzed C-H activation, especially the development of transition-metal-catalyzed chelation-assisted C-H activation. Then, a more detailed discussion is directed towards our recent studies on the transition-metal-catalyzed chelation-assisted oxidative C-H/C-H functionalization of aromatic substrates bearing directing functional groups.

The development and validation of the Chinese safety climate scale using the item-response theory approach.

Introduction: To develop a valid and practical tool to measure the safety climate in China, and further raise awareness of it in Chinese industries, we developed the Chinese safety climate scale (including two subscales at the levels of organization and group separately) based on the work of Huang et al. in 2017. Methods: A descriptive survey with the convenience sampling method was conducted in Shanghai Disney Resort, China. A sample of 1,570 employees was involved in the final data analyses. The item response theory (IRT) analyses with graded response models were conducted using. Results: The unidimensionality and local independence assumption were held. The Cronbach's α of organization- and group- level safety climate subscale was 0.912 and 0.937, respectively. The confirmatory factor analysis (CFA) showed good model fit for a one-factor model of the organization-level safety climate subscale, χ2 (df = 20) = 129.158, p < 0.001, CFI = 0.994, TLI = 0.992, NFI = 0.993, IFI = 0.994, RMSEA = 0.059, 90% CI = (0.050, 0.069), and SRMR = 0.048. A one-factor model also fits well for the group-level safety climate subscale, χ2 (df = 44) = 219.727, p < 0.001, CFI = 0.996, TLI = 0.9925, NFI = 0.995, IFI = 0.996, RMSEA = 0.050, 90% CI = (0.044, 0.057), and SRMR = 0.046. Discrimination and difficulty parameters showed that all items effectively spanned the range of the latent trait and could successfully separate participants at different safety climate levels. Items in the organization-level and group-level Chinese safety climate subscales had significantly different discrimination parameters, fitted well with the models, and had a substantive relationship with the latent traits. Discussion: The Chinese safety climate scale was reliable and valid overall. They can facilitate the research and survey regarding the safety climate in China.

Palladium-Catalyzed Synthesis of Esters from Arenes through C-H Thianthrenation.

The efficient palladium-catalyzed synthesis of esters from readily available arenes has been developed. These C-H bond esterifications were achieved relying on the regioselective thianthrenation to generate the aryl-TT salts, which were treated as reactive electrophilic substrates to couple with phenol formate and N-hydroxysuccinimide (NHS) formate giving access to phenol esters and NHS esters, respectively, in the absence of carbon monoxide. A wide range of functional esters could be prepared with high efficiency under this redox-neutral palladium-catalytic condition. Late-stage functionalization and investigations of synthetic applications demonstrated the potential application of the established platform and these products.

Synthesis of ß-Polychlorinated Alkynes Enabled by Copper-Catalyzed Multicomponent Reaction.

Functional molecules bearing polychlorinated moieties usually play versatile roles in organic synthesis and biochemistry. A copper-catalyzed multicomponent polychloro-carboalkynylation of alkenes presents an efficient and operationally simple approach for the synthesis of ß-polychlorinated alkynes. Mechanistic experiments were conducted demonstrating that an in situ generated copper acetylide complex was the real catalyst and reactive intermediate during the copper-catalytic cycle. And enantioselective exploration demonstrated potential application for the synthesis of chiral ß-polychlorinated alkynes.

Palladium-Catalyzed Synthesis of C-1 Deuterated Aldehydes from (Hetero) Arenes Mediated by C (sp2)-H Thianthrenation.

A palladium-catalyzed deuterated formylation of aryl sulfonium salts is prepared conveniently from readily available arenes, which enables the expedient synthesis of a series of structurally diverse C-1 deuterated aldehydes with 96%-99% deuterium incorporation. The easy to handle and cost-effective DCOONa provides a deuterium source, which can be introduced onto the formyl units with excellent selectivity under the palladium-catalytic redox neutral conditions. This catalytic route can accomplish the direct late-stage C-H functionalization of bioactive molecules and natural product derivatives assisted by C (sp2)-H thianthrenation. Moreover, on the basis of this practical approach, several deuterated drugs and analogues could be prepared with excellent levels of deuterium incorporation.

Copper-catalysed Csp3-Csp cross-couplings between cyclobutanone oxime esters and terminal alkynes induced by visible light.

A novel transformation for the construction of Csp3-Csp bonds was achieved via a photo-induced copper-catalysed C-C bond cleavage. This approach was applied to prepare a series of highly functionalized alkynyl nitriles using readily available cyclobutanones and terminal alkynes. Mechanistic exploration showed that the in situ generated copper acetylide complex is an effective photosensitive catalyst to promote the C-C bond cleavage of cycloketoxime esters through a radical process.

Boron-mediated directed aromatic C-H hydroxylation.

Transition metal-catalysed C-H hydroxylation is one of the most notable advances in synthetic chemistry during the past few decades and it has been widely employed in the preparation of alcohols and phenols. The site-selective hydroxylation of aromatic C-H bonds under mild conditions, especially in the context of substituted (hetero)arenes with diverse functional groups, remains a challenge. Here, we report a general and mild chelation-assisted C-H hydroxylation of (hetero)arenes mediated by boron species without the use of any transition metals. Diverse (hetero)arenes bearing amide directing groups can be utilized for ortho C-H hydroxylation under mild reaction conditions and with broad functional group compatibility. Additionally, this transition metal-free strategy can be extended to synthesize C7 and C4-hydroxylated indoles. By utilizing the present method, the formal synthesis of several phenol intermediates to bioactive molecules is demonstrated.

Radical-induced ring-opening and reconstruction of cyclobutanone oxime esters.

The first example of intramolecular ring-opening and reconstruction of cyclobutanone oxime esters via selective C-C bond cleavage leading to the synthesis of 3,4-dihydronaphthalene-2-carbonitriles in the presence of a cheap copper catalyst has been reported. The protocol is distinguished by mild and safe reaction conditions that exclude ligands, oxidants, bases, toxic cyanide salts and tolerates a wide scope of cyclobutanones without compromising their efficiency and scalability. The alternative visible-light-driven photoredox process for this coupling reaction was also uncovered.