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Summary Transition-metal-catalyzed carbonylative reaction is an efficient approach to construct carbonyl-containing compounds with a high atomic economy in modern organic synthesis. This review focuses on the transition-metal-catalyzed carbonylation of aliphatic carbon nucleophiles. The carbonylation reactions with alkyl carbon nucleophiles, including alkyl boranes, tetraalkyltins, alkylzinc, trialkyl aluminium, alkylindium, and alkylzirconium reagents have been summarized and discussed here.

Herein, we reported an efficient and sustainable intramolecular electrochemical cyclization of N-allylcarboxamides for the synthesis of various halogenated oxazolines. This method was conducted in a simple undivided cell by employing lithium halogen salts as redox mediums and halogen sources. A wide range of oxazolines, including five- and six-membered heterocycles, iodine-, bromo-, and chloro-methyl oxazolines were constructed in moderate to good yields at room temperature. Notably, this electrochemical oxidative cyclization obviates the use of external oxidants.

The occurrence and transmission of chirality is a fascinating characteristic of nature. However, the intermolecular transmission efficiency of circularly polarized luminescence (CPL) remains challenging due to poor through-space energy transfer. We report a unique CPL transmission from inducing the achiral acceptor to emit CPL within a specific liquid crystal (LC)-based intermolecular system through a circularly polarized fluorescence resonance energy transfer (C-FRET), wherein the luminescent cholesteric LC is employed as the chirality donor, and rationally designed achiral long-wavelength aggregation-induced emission (AIE) fluorophore acts as the well-assembled acceptor. In contrast to photon-release-and-absorption, the chirality transmission channel of C-FRET is highly dependent upon the energy resonance in the highly intrinsic chiral assembly of cholesteric LC, as verified by deliberately separating the achiral acceptor from the chiral donor to keep it far beyond the resonance distance. This C-FRET mode provides a de novo strategy concept for high-level information processing for applications such as high-density data storage, combinatorial logic calculation, and multilevel data encryption and decryption.

A facile synthesis of 4H-benzo[d][1,3]oxazin-4-one derivatives by Pd-catalyzed carbonylative cross-coupling between N-(ortho-bromoaryl)amides and benzene-1,3,5-triyl triformate (TFBen) was developed. This procedure does not require the toxic and flammable gas CO as the carbonyl source and tolerates a wide scope of functional groups. Remarkably, 4H-benzo[d][1,3]oxazin-4-ones incorporated to natural products and drugs can be constructed by this method.

The unique properties of fluorine-containing organic compounds make fluorine substitution attractive for the development of pharmaceuticals and various specialty materials, which have inspired the evolution of diverse C-F bond activation techniques. Although many advances have been made in functionalizations of activated C-F bonds utilizing transition metal complexes, there are fewer approaches available for nonactivated C-F bonds due to the difficulty in oxidative addition of transition metals to the inert C-F bonds. In this regard, using Lewis acid to abstract the fluoride and light/radical initiator to generate the radical intermediate have emerged as powerful tools for activating those inert C-F bonds. Meanwhile, these transition-metal-free processes are greener, economical, and for the pharmaceutical industry, without heavy metal residues. This review provides an overview of recent C-F bond activations and functionalizations under transition-metal-free conditions. The key mechanisms involved are demonstrated and discussed in detail. Finally, a brief discussion on the existing limitations of this field and our perspective are presented.

Functionalized bisboryl compounds have recently emerged as a new class of synthetically useful building blocks in organic synthesis. Herein, we report an efficient strategy to synthesize β-geminal-diboryl ketones enabled by a Cu/Pd-catalyzed borocarbonylative trifunctionalization of readily available alkynes and allenes. This reaction promises to be a useful method for the synthesis of functionalized β-geminal-diboryl ketones with broad functional group tolerance. Mechanistic studies suggest that the reaction proceeds through borocarbonylation/hydroboration cascade of both alkynes and allenes.

A nickel-catalyzed one-pot carbonylation reaction of 2-bromobenzenesulfonyl chlorides with alkynes for the synthesis of thiochromenones has been established. Both terminal and internal alkynes were suitable substrates in this carbonylative transformation, and a broad range of 2-mono- and 2,3-disubstituted thiochromenone products were obtained in moderate to good yields with quite high functional group compatibility. Notably, this procedure presents the first example of nickel-catalyzed carbonylative synthesis of thiochromenones with 2-bromobenzenesulfonyl chlorides as a promising sulfur precursor.

A palladium supported on graphitic carbon nitride (Pd/g-C3 N4 ) catalyzed carbonylative reaction of aryl bromides and arylboronic acids by has been developed for the construction of diaryl ketones. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source, the reaction proceeded well to give various diaryl ketones in moderate to good yields.

The addition reaction between CuBpin and alkenes to give a terminal boron substituted intermediate is usually fast and facile. In this communication, a selectivity-reversed procedure has been designed and established. This selectivity-reversed borocarbonylation reaction is enabled by a cooperative action between palladium and copper catalysts and proceeds with complete regioselectivity. The key to the success of this transformation is the coordination of the amide group and slower CuBpin formation by using KHCO3 as the base. A wide range of β-boryl ketones were produced from terminal unactivated aliphatic alkenes and aryl iodides. Further synthetic transformations of the obtained β-boryl ketones have been developed as well., A selectivity-reversed borocarbonylation reaction has been developed with complete regioselectivity.

The development of novel redox system is of great significance to the development of organic chemistry. Herein, BiIII/BiV involved redox intermediates has been developed for the oxidative carbonylative coupling of triarylbismuthines. Possible intermediates were prepared and studied. The ArC(O)-BiV species formed by CO insertion proved as the key to reductive elimination progress for the final products formation. Intermolecular aryl exchange between bismuth reagents was also discovered. A most possible reaction mechanism is proposed.

β-Boryl amide is a class of high value intermediates in organic chemistry. In this work, a copper-catalyzed carbonylative boroamidation of olefins toward the synthesize of β-boryl amides has been d...

Background: Arthritis is a cartilage degenerative disease that is mainly induced by the degradation of the cartilage extracellular matrix (ECM), which is found to be regulated by the expression level of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMT-5), an enzyme degrading Aggrecans in the ECM. Feprazone is a classic nonsteroidal anti-inflammatory drug with promising efficacy in arthritis. The present study aims to investigate the protective effect of Feprazone on the degraded Aggrecan in the human chondrocytes induced with tumor necrosis factor-α (TNF-α) and to clarify the underlying mechanism. Methods: To investigate the effect of Feprazone, the CHON-001 chondrocytes were stimulated with TNF-α (10 ng/mL) in the presence or absence of Feprazone (3, 6 μM) for 24 h. Mitochondrial membrane potential was evaluated using the Rhodamine 123 assay. The gene expressions of interleukin-1β (IL-1β), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and ADAMTS-5 in the treated chondrocytes were detected using real-time quantitative polymerase chain reaction (qRT-PCR), and the protein levels of these targets were determined using enzyme-linked immunosorbent assay (ELISA). SOX-4 was knocked down by transfecting the siRNA into the chondrocytes. Western blot analysis was utilized to evaluate the expression levels of SOX-4, Aggrecan, and protein kinase C (PKCα). Results: First, the reduced mitochondrial membrane potential (ΔΨm) and secretion of proinflammatory factors (IL-1β, IL-8, and MCP-1) induced by TNF-α were significantly reversed by treatment with Feprazone. Second, the expression of Aggrecan was significantly decreased by stimulation with TNF-α via upregulation of ADAMTS-5 but was dramatically reversed by the introduction of Feprazone. Third, we found that TNF-α elevated the expression of ADAMTS-5 by upregulating SOX-4, which was observed to be related to the activation of PKCα. Lastly, the elevated expression of SOX-4 induced by TNF-α was significantly reversed by Feprazone. Conclusions: Feprazone might ameliorate TNF-α-induced loss of Aggrecan via the inhibition of the SOX-4/ADAMTS-5 signaling pathway.

A nickel-promoted cascade annulation reaction for the facile synthesis of 3H-1,2,4-triazol-3-ones from readily available hydrazonoyl chlorides and sodium cyanate has been developed. The transformation occurs through a cascade nickel-promoted intermolecular nucleophilic addition-elimination process, intramolecular nucleophilic addition, and a hydrogen-transfer sequence. The method has been successfully applied for the construction of the core skeleton of the angiotensin II antagonist.

Thiocarbonylation of alkenes offers an ideal procedure for the synthesis of thioesters. However, thiocarbonylation of alkenes, especially styrenes, to produce valuable linear thioesters has remaine...

The palladium-catalyzed oxidative carbonylation of amines toward the synthesis of oxalamides has been established around 30 years ago and it usually needs the presence of (over)stoichiometric amounts of oxidant. In this work, the first transformation of this type in which the oxidant was replaced by visible light is described. The new approach uses a simple robust Pd complex, which can even be partially recycled. A mechanistic reason is provided and supported by control experiments and EPR studies, showing that PdI was formed and Pd0 was the active species. Both nitrogen- and the intermediate acyl radical can be detected. Moreover, the formation of hydrogen was confirmed by gas GC.

A silver-mediated [3 + 2] cycloaddition of azomethine ylides with trifluoroacetimidoyl chlorides for the rapid assembly of 5-(trifluoromethyl)imidazoles has been developed. Notable features of the reaction include readily accessible reagents, a broad substrate scope, and high efficiency. The protocol can be successfully applied to construct the analogue of the specific allosteric modulator of GABA

A palladium-catalyzed three-component carbonylative reaction for the synthesis of 3H-1,2,4-triazol-3-ones from hydrazonoyl chlorides and NaN3 has been achieved. The reaction presumably proceeds through a cascade carbonylation, acyl azide formation, Curtius rearrangement, and intramolecular nucleophilic addition sequence. A wide variety of structurally diverse 3H-1,2,4-triazol-3-ones were constructed in moderate to excellent yields. Benzene-1,3,5-triyl triformate (TFBen) was applied as a solid and convenient CO surrogate.

Dimethyl carbonate (DMC), an environment-friendly compound prepared from CO2, shows diverse reactivities. In this communication, an efficient procedure using DMC as both a C1 building block and solvent in the aminocarbonylation reaction with nitro compounds has been developed. W(CO)6 acts both a CO source and a reductant here.

A nickel-catalyzed carbonylative cyclization of 2-nitroalkynes and aryl iodides has been developed for the expedite construction of N-benzoyl indole scaffolds. Using Co2(CO)8 as the CO source, this cascade reaction proceeded with high efficiency to give a variety of N-benzoyl indoles in moderate to high yields. Control experiments were performed as well to gain a better understanding of the reaction mechanism.

A palladium-catalyzed carbonylation of iminoquinones and aryl iodides has been developed for the construction of aryl p-amino benzoates. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source, the reaction proceeded well to give various aryl p-amino benzoates in good to excellent yields. Additionally, control experiments were conducted to gain more insights into the reaction mechanism.

Herein, a facile and straightforward route to synthesize 3-trifluoromethyl-1,2,4-triazoles via copper-mediated [3 + 2] cycloaddition of trifluoroacetimidoyl chlorides and N-isocyanoiminotriphenylphosphorane (NIITP) has been described. Mo(CO)6 is utilized as an effective promotor to activate NIITP. The transformation features readily accessible reagents, mild reaction conditions, a broad substrate scope and high efficiency, and could be reproducible on a 3 mmol scale.

A palladium-catalyzed three-component carbonylative reaction of trifluoroacetimidohydrazides and aryl iodides for the synthesis of pharmaceutically valuable 5-trifluoromethyl-1,2,4-triazoles has been achieved. The reaction is characterized by a low catalyst loading amount, a broad substrate scope, high efficiency, no participation of CO gas and good application prospects. The protocol has been successfully applied to prepare the bioactive molecule GlyT1 inhibitor.

A palladium-catalyzed regioselective cyclocarbonylation of N-(2-pyridyl)sulfonyl (N-SO2Py)-2-iodoanilines with allenes has been developed. With the assistance of the directing group N-SO2Py, the regioselectivity of arylallenes was reversed and the reaction proceeded well to give various 3-methylene-2,3-dihydroquinolin-4(1H)-ones with up to 95% yield by using benzene-1,3,5-triyl triformate (TFBen) as the CO source. Control experiments and DFT calculations were performed to understand the reaction details and a possible reaction mechanism is proposed accordingly.

A nickel-catalyzed reductive aminocarbonylation reaction for the synthesis of α,β-unsaturated amides has been described. By employing vinyl triflates and nitroarenes as readily available starting materials, a wide range of α,β-unsaturated amide products were obtained in moderate to excellent yields with very good functional group tolerance in the absence of an external reductant. Notably, this is the first example of carbonylative synthesis of α,β-unsaturated amides by applying a Ni/Mo(CO)6 catalytic system with nitroarenes as promising nitrogen precursors. In addition, a late-stage modification of natural products was also achieved via this reductive aminocarbonylation approach.

The construction of structurally complexed and high-value chemical molecules from simple and readily available feedstocks is a long-standing challenge to chemists. Here, we describe a copper-catalyzed borofunctionalization of styrenes with B2pin2 and carbon monoxide. A set of new sodium cyclic borates were obtained with NaOtBu as the base. These unique sodium cyclic borates can be easily converted into a variety of multifunctional β-boryl vinyl esters, boryl carbonates, β-boryl aldehydes, and boryl vinyl ether. In addition, the procedure also features good functional group tolerance and utilizes CO as the C1 source.

A palladium-catalyzed 1,2-amino carbonylation of 1,3-dienes with (N-SO2Py)-2-iodoanilines has been developed for the construction of 2,3-dihydroquinolin-4(1H)-one scaffolds. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source under the assistance of the N-SO2Py directing group, the reaction proceeded well to afford various 2,3-dihydroquinolin-4(1H)-ones in good yields (up to 88%). The effect of the directing groups was investigated and control experiments were performed to have a better understanding of the reaction pathway.

In this communication, a transition-metal-free deaminative carbonylation of activated alkylamines with thiophenols has been developed. Thioesters with various substituents were produced in moderate to good yields through Katritzky salt intermediates.

A cobalt-catalyzed domino Pauson–Khand and [4 + 2] cycloaddition of substituted diynes has been developed for the rapid construction of complexed polycyclic ring systems. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source, the reaction proceeded well to give various tetracyclic compounds bearing two new quaternary carbon cores in high yields with excellent regioselectivity and diastereoselectivity. Control experiments were performed to gain a better understanding of the reaction mechanism.

A metal-free oxidative cyclization of trifluoroacetimidohydrazides with methylhetarenes for the efficient synthesis of 3-hetaryl-5-trifluoromethyl-1,2,4-triazoles has been developed. Notable features of this protocol include readily accessible starting materials, a broad substrate scope, high efficiency and scalability. The transformation provides a facile and straightforward route to valuable multi-functionalized 1,2,4-triazole derivatives.

A palladium-catalyzed carbonylative synthesis of N-acyl indoles from 2-alkynylanilines and aryl iodides has been developed. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source, the reaction produced a variety of N-acyl indoles in a facile manner with high yields.

How to make a carbonylative coupling faster than the easier nucleophilic substitution? In this communication, a rhodium-catalyzed radical-based carbonylative coupling of alkyl halides with thiolphenols has been realized. Thioesters were isolated in good yields in general.