Carbonylation Reactions at Carbon-Centered Radicals with an Adjacent Heteroatom.

Heteroatoms are essential to living organisms and present in almost all molecules with medicinal usage. The catalytic functionalization at the carbon-centered radical with an adjacent heteroatom provides an effective way to value added moiety while retaining the unique physicochemical and pharmacological properties of heteroatoms, which can promote the development of pharmaceutical and fine chemical production. Carbonylative transformation was discovered nearly a century ago which is an efficient method for the synthesis of carbonyl-containing molecules with potent applications in both industry and academia. Despite numerous advances in new reaction development, carbonylative transformation involving adjacent heteroatom carbon radical remain a subject that deserves to be discussed. In this minireview, we systematically summarized and discussed the recent advances in carbonylative transformations involving carbon-centered radicals with an adjacent heteroatom, including oxygen (O), nitrogen (N), phosphorus (P), silicon (Si), sulfur (S), boron (B), fluorine (F), and chlorine (Cl). The related reaction mechanism was also discussed.

Cobalt-Catalyzed Direct Aminocarbonylation of Ethers: Efficient Access to α-Amide Substituted Ether Derivatives.

Ethers are of central importance in the fields of biomass, energy, and organic chemistry. Herein, a novel cobalt-catalyzed carbonylative coupling of ethers with amines to construct α-carbonylated ethers has been achieved. Remarkably, Alfuzosin, a medicine for treatment of benign prostatic hyperplasia (BPH), can be synthesized by this process straightforwardly. Notably, this protocol presents the first example on the direct carbonylative reaction of ethers.

Nickel-Catalyzed Four-Component Carbonylation of Ethers and Olefins: Direct Access to γ-Oxy Esters and Amides.

Multi-component carbonylation of olefins, a reaction that installs both a carbon-carbon(heteroatom) bond and a carbonyl group across the double bond, is an attractive strategy for alkene functionalization. Herein, we developed a novel nickel-catalyzed four-component carbonylation of olefins with ethers under low CO gas pressure. Using alcohols and amines as the reaction partner, diverse γ-oxy-substituted esters and amides were produced in good yields with excellent functional group tolerance. Notably, Naftidrofuryl, a medicine for the treatment of cerebrovascular disease (CVD), can be synthesized by this process straightforwardly.

The cascade coupling/iodoaminocyclization reaction of trifluoroacetimidoyl chlorides and allylamines: metal-free access to 2-trifluoromethyl-imidazolines.

A metal-free cascade coupling/iodoaminocyclization reaction for the rapid assembly of 2-trifluoromethyl-imidazolines has been disclosed. The transformation applies readily accessible trifluoroacetimidoyl chlorides, allylamines and N-iodosuccinimides as the starting substrates, achieving an efficient and straightforward pathway to construct diverse imidazoline derivatives. Excellent efficiency of the reaction is observed (higher than 90% isolated yield for half of the examples), and the obtained imidazoline products bearing a pendent iodomethyl group could be easily transformed into other synthetically valuable compounds.

Equation of state and first principles prediction of the vibrational matrix shift of solid parahydrogen.

We generate the equation of state (EOS) of solid parahydrogen (para-H2) using a path-integral Monte Carlo (PIMC) simulation based on a highly accurate first-principles adiabatic hindered rotor potential energy curve for the para-H2 dimer. The EOS curves for the fcc and hcp structures of solid para-H2 near the equilibrium density show that the hcp structure is the more stable of the two, in agreement with experiment. To accurately reproduce the structural and energy properties of solid para-H2, we eliminated by extrapolation the systematic errors associated with the choice of simulation parameters used in the PIMC calculation. We also investigate the temperature dependence of the EOS curves, and the invariance of the equilibrium density with temperature is satisfyingly reproduced. The pressure as a function of density and the compressibility as a function of pressure are both calculated using the obtained EOS and are compared with previous simulation results and experiments. We also report the first ever a priori prediction of a vibrational matrix shift from first-principles two-body potential functions, and its result for the equilibrium state agrees well with experiment.

Photoredox-catalyzed carbonylative acylation of styrenes with Hantzsch esters.

Ketones exist widely in naturally occurring products and are indispensable building blocks in organic synthesis. Carbonylation represents one of the most straightforward methods for ketone preparation and has become an attractive field in modern organic chemistry as well. Among the strategies, photocatalytic carbonylation is also worthy of further exploration. Herein, we developed a three-component carbonylation that provides a new method for the synthesis of ketones from Hantzsch esters, CO and styrenes. The reaction was performed under a blue light environment and yields a series of ketones with moderate to good yields.

Visible light induced cooperative carbonylation and (hetero)aryl migration: synthesis of multi-carbonyl compounds.

Carbonylative transformation represents one of the most straightforward procedures for the synthesis of carbonyl-containing compounds. However, the carbonylative procedure toward 1,4-diketones is still limited which are key moieties with potent applications in various areas. Herein, we report a new strategy for the synthesis of multi-carbonyl compounds containing a 1,4-diketone skeleton through remote heteroaryl migration of traditionally restricted 1,3-migratory substrates utilizing carbon monoxide (CO) as the C1 synthon and diazonium compounds as the starting material.

Iron-Catalyzed Aminoalkylative Carbonylative Cyclization of Alkenes toward α-Tetralones.

Carbonylative multifunctionalization of alkenes is an efficient approach to introduce multiple functional groups into one molecule from easily available materials. Herein, we developed an iron-catalyzed radical relay carbonylative cyclization of alkenes with acetamides. Various α-tetralones can be constructed in moderate yields from readily available substrates with an earth-abundant iron salt as the catalyst.

A new six-dimensional potential energy surface for H2-N2O and its adiabatic-hindered-rotor treatment.

A six-dimensional ab initio potential energy surface (PES) for H2-N2O which explicitly includes the symmetric and asymmetric vibrational coordinates Q1 and Q3 of N2O is calculated at the coupled-cluster singles and doubles with noniterative inclusion of connected triple level using an augmented correlation-consistent polarized-valence quadruple-zeta basis set together with midpoint bond functions. Four-dimensional intermolecular PESs are then obtained by fitting the vibrationally averaged interactions energies for υ3(N2O) = 0 and 1 to the Morse∕long-range analytical form. In the fits, fixing the long-range parameters at theoretical values smoothes over the numerical noise in the ab initio points in the long-range region of the potential. Using the adiabatic hindered-rotor approximation, two-dimensional PESs for hydrogen-N2O complexes with different isotopomers of hydrogen are generated by averaging the 4D PES over the rotation of the hydrogen molecule within the complex. The band-origin shifts for the hydrogen-N2O dimers calculated using both the 4D PESs and the angle-averaged 2D PESs are all in good agreement with each other and with the available experimental observations. The predicted infrared transition frequencies for para-H2-N2O and ortho-D2-N2O are also consistent with the observed spectra.

Site-selective carbonylation of arenes via C(sp2)-H thianthrenation: direct access to 1,2-diarylethanones.

Herein, a new reaction for the site-selective carbonylation of arenes via C(sp2)-H thianthrenation under mild conditions has been developed. With low loadings of palladium catalysts, various desired 1,2-diarylethanones are produced in good yields. This strategy also enables the late-stage modification of complex molecules, which was previously challenging with similar carbonylative Negishi-type reactions.

Copper-Catalyzed Direct Carbonylation of Carbenes toward the Synthesis of Propanedioic Acid Derivatives.

Carbenes are highly active reaction intermediates, which can be used as reaction precursors to modify organisms, drugs, and material molecules. In this work, we realized a new cheap metal-catalyzed carbonylation of carbene to give propanedioic acid derivatives. With copper salt as the catalyst, synthetically important malonates and related compounds were produced in good yields under mild reaction conditions.

Cobalt-catalyzed aminoalkylative carbonylation of alkenes toward direct synthesis of γ-amino acid derivatives and peptides.

γ-Amino acids and peptides analogues are common constituents of building blocks for numerous biologically active molecules, pharmaceuticals, and natural products. In particular, γ-amino acids are providing with better metabolic stability than α-amino acids. Herein we report a multicomponent carbonylation technology that combines readily available amides, alkenes, and the feedstock gas carbon monoxide to build architecturally complex and functionally diverse γ-amino acid derivatives in a single step by the implementation of radical relay catalysis. This transformation can also be used as a late-stage functionalization strategy to deliver complex, advanced γ-amino acid products for pharmaceutical and other areas.

Cobalt-Catalyzed Carbonylative Synthesis of 4-Oxobutanoates from Formamide and Ethylene.

The direct concurrent installation of amide and ester groups across olefin motifs represents a powerful and promising functionalization tool in organic chemistry. Herein, a ligand-free cobalt-catalyzed four-component radical relay carbonylative difunctionalization of ethylene for the synthesis of 4-oxobutanoates has been developed. Valuable C4 building blocks were produced in a highly atom-economical fashion.

Type II Toxin-Antitoxin Systems in Pseudomonas aeruginosa.

Toxin-antitoxin (TA) systems are typically composed of a stable toxin and a labile antitoxin; the latter counteracts the toxicity of the former under suitable conditions. TA systems are classified into eight types based on the nature and molecular modes of action of the antitoxin component so far. The 10 pairs of TA systems discovered and experimentally characterised in Pseudomonas aeruginosa are type II TA systems. Type II TA systems have various physiological functions, such as virulence and biofilm formation, protection host against antibiotics, persistence, plasmid maintenance, and prophage production. Here, we review the type II TA systems of P. aeruginosa, focusing on their biological functions and regulatory mechanisms, providing potential applications for the novel drug design.

LncIRF1 promotes chicken resistance to ALV-J infection.

The pathogenesis of avian leukosis virus subgroup J (ALV-J) is complex and our understanding of it is limited. Based on our previous research, we explored the relationship between ALV-J infection and regulatory factor 1&7 (IRF1 and IRF7), interferon beta (IFNß), and the newly identified long noncoding RNA IRF1 (LncIRF1). LncIRF1 is 1603 nt and exists in the cytoplasm and nucleus. After the occurrence of ALV-J infection, the expression levels of LncIRF1, IRF1, IRF7, and IFNß varied in different chicken tissues. In DF1 cell lines of chicken embryo fibroblast cells (DF1 cells) the expression levels of LncIRF1, IRF7, IRF1, and IFNß increased when ALV-J infection. Similarly, after LncIRF1 overexpression and the ALV-J challenge, the expression levels of IRF1, IRF7, and IFNß increased, while increased LncIRF1 inhibited the proliferation of DF1 cells. Interference with LncIRF1 did not affect IRF1, IRF7, and IFNß. However, expression levels of IRF1, IRF7, and IFNß decreased due to LncIRF1 interference after the ALV-J challenge. An assay of the RNA-binding domain abundant in apicomplexans indicated that most of the proteins bound to LncIRF1 are related to cell proliferation and viral replication and these proteins also interact with IRF1, IRF7, and IFNß. We suggest that LncIRF1 plays an important immunomodulatory role in the anti-ALV-J response. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03773-y.

Finite temperature path integral Monte Carlo simulations of structural and dynamical properties of Ar(N)-CO2 clusters.

We report finite temperature quantum mechanical simulations of structural and dynamical properties of Ar(N)-CO(2) clusters using a path integral Monte Carlo algorithm. The simulations are based on a newly developed analytical Ar-CO(2) interaction potential obtained by fitting ab initio results to an anisotropic two-dimensional Morse/Long-range function. The calculated distributions of argon atoms around the CO(2) molecule in Ar(N)-CO(2) clusters with different sizes are consistent to the previous studies of the configurations of the clusters. A first-order perturbation theory is used to quantitatively predict the CO(2) vibrational frequency shift in different clusters. The first-solvation shell is completed at N = 17. Interestingly, our simulations for larger Ar(N)-CO(2) clusters showed several different structures of the argon shell around the doped CO(2) molecule. The observed two distinct peaks (2338.8 and 2344.5 cm(-1)) in the υ(3) band of CO(2) may be due to the different arrangements of argon atoms around the dopant molecule.

A new four-dimensional ab initio potential energy surface for N2O-He and vibrational band origin shifts for the N2O-He(N) clusters with N = 1-40.

A new four-dimensional ab initio potential energy surface for N(2)O-He is constructed at the CCSD(T) level with an aug-cc-pVQZ basis set together with bond functions. The vibrational coordinates Q(1) and Q(3) of N(2)O are explicitly included, due to the strong coupling between the symmetric and asymmetric stretches of N(2)O. A global potential energy surface is obtained by fitting the original potential points to a four-dimensional Morse∕long range (MLR) analytical form. In the fitting, the ab initio noise in the long range region of the potential is smoothed over by theoretically fixed long range parameters. Two-dimensional intermolecular potentials for both the ground and the excited υ(3) states of N(2)O are then constructed by vibrationally averaging the four-dimensional potential. Based on the two-dimensional potentials, we use the path integral Monte Carlo algorithm to calculate the vibrational band origin shifts for the N(2)O-He(N) clusters using a first order perturbation theory estimate. The calculated shifts agree reasonably well with the experimental values and reproduce the evolution tendency from dimer to large clusters.

Non-Noble Metal-Catalyzed Carbonylative Multi-Component Reactions.

Carbonylative multi-component reactions (CMCR), having four or more kinds of starting materials, provide an efficient strategy for the preparation of polyfunctional carbonylated compounds. Diverse CMCR utilizing non-noble transition-metal catalysts have been developed. This review summarized and discussed the recent advances in non-noble metal-catalyzed carbonylative multi-component reactions.

Palladium-Catalyzed Desulfonative Carbonylation of Thiosulfonates: Elimination of SO2 and Insertion of CO.

A palladium-catalyzed desulfonative carbonylation of thiosulfonates has been explored. Without any additive, a series of S-aryl/alkyl benzenesulfonothioates were successfully transformed to thioesters in moderate to excellent yields by SO2 extrusion and CO insertion under the pressure of 1 bar of CO. The solvent dimethylacetamide (DMAc) facilitated this desulfonative carbonylation due to its high absorbing ability of SO2.

Controllable access to trifluoromethyl-containing indoles and indolines: palladium-catalyzed regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides.

The synthesis of diverse products from the same starting materials is always attractive in organic chemistry. Here, a palladium-catalyzed substrate-controlled regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides has been developed, which provides a direct but controllable access to a variety of structurally diverse trifluoromethyl-containing indoles and indolines. In more detail, with respect to γ,δ-alkenes, 1,1-geminal difunctionalization of unactivated alkenes with trifluoroacetimidoyl chloride enables the [4 + 1] annulation to produce indoles; as for ß,γ-alkenes, a [3 + 2] heteroannulation with the hydrolysis product of trifluoroacetimidoyl chloride through 1,2-vicinal difunctionalization of alkenes occurs to deliver indoline products. The structure of alkene substrates differentiates the regioselectivity of the reaction.