Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Copper-catalyzed trichloromethylative carbonylation of ethylene.

Difunctionalization of alkenes is an efficient strategy for the synthesis of complex compounds from readily available starting materials. Herein, we developed a copper-catalyzed visible-light-mediated trichloromethylative carbonylation of ethylene by employing commercially available CCl4 and CO as trichloromethyl and carbonyl sources, respectively. With this protocol, various nucleophiles including amines, phenols, and alcohols can be rapidly transformed into ß-trichloromethyl carboxylic acid derivatives with good functional-group tolerance. Bis-vinylated γ-trichloromethyl amides can also be obtained by adjusting the pressure of carbon monoxide and ethylene. In addition, this photocatalytic system can be successfully applied in the late-stage functionalization of bioactive molecules and pharmaceutical derivatives as well.

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.

Photo-Induced Carbonylation of Aryl Bromides for the Synthesis of Aryl Esters and Amides Under Transition Metal-Free Conditions.

In this work, we developed a photo-induced carbonylation of aryl bromides under transition metal-free conditions. The reaction shows good activity with alcohol and amine nucleophiles. Various esters and amides were formed from aryl halides and alcohols and amines under mild conditions in moderate to good yields.

Regioselective and Enantioselective Copper-Catalyzed Hydroaminocarbonylation of Unactivated Alkenes and Alkynes.

Given the prevalence of amide backbones in marketed pharmaceuticals and their ubiquity as critical binding units in natural peptides and proteins, it remains important to develop novel methods to construct amide bonds. We report here a general method for the anti-Markovnikov hydroaminocarbonylation of unactivated alkenes under mild conditions, using copper catalysis in combination with hydroxylamine electrophile reagents and poly(methylhydrosiloxane) (PMHS) as a cheap and environmentally friendly hydride source. The reaction tolerates a variety of functional groups and efficiently converts unactivated terminal alkenes, 1,1-disubstituted alkenes, and cyclic alkenes to the corresponding amides with exclusive anti-Markovnikov selectivity (and high enantioselectivities/diastereoselectivities). Additionally, with minimal modification of the reaction conditions, alkynes can also undergo tandem hydrogenation-hydroaminocarbonylation to alkyl amides.

Palladium-Catalyzed Perfluoroalkylative Carbonylation of 2-Allylaryl Trifluoromethanesulfonates: Base-Controlled Selective Access to ß-Perfluoroalkyl Amides.

A palladium-catalyzed perfluoroalkylative carbonylation of 2-allylaryl trifluoromethanesulfonates has been developed. A range of 2-allyl trifluoromethanesulfonates, perfluoroalkyl halides, and amines were applied in this tandem procedure to provide the corresponding ß-perfluoroalkyl amides with good functional group tolerance and high chemoselectivity. The final products were controlled by the base applied.

Palladium-catalyzed difluoroalkylative carbonylation of styrenes toward difluoropentanedioates.

The introduction of fluorine atoms into organic molecules is an attractive but challenging topic. In this work, an interesting palladium-catalyzed difluoroalkylative carbonylation of aryl olefins has been developed. A wide range of aryl olefins were transformed into the corresponding difluoropentanedioate compounds with good functional-group tolerance and excellent regioselectivity. Inexpensive ethyl bromodifluoroacetate acts both as a difluoroalkyl precursor and a nucleophile here. Additionally, a scale-up reaction was also performed successfully, and further transformations of the obtained product were shown as well.

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.

Palladium-Catalyzed Carbonylative Four-Component Synthesis of ß-Perfluoroalkyl Amides.

Transition-metal-catalyzed multicomponent carbonylation is one of the most efficient strategies to construct carbonyl-containing compounds. Herein, a palladium-catalyzed four-component perfluoroalkylation/aminocarbonylation of unactivated alkenes with perfluoroalkyl halides, and amines was developed. A wide range of substrates, including anilines, alkylamines, sulfonamides, and hydrazines are all suitable reaction partners for this catalyst system, resulting in various ß-perfluoroalkyl amides with good functional-group tolerance and excellent chemoselectivity. Furthermore, not only alkyl olefins, but also aliphatic alkynes, and even alkyl allenes can all be employed. Notably, several medical and bioactive related molecules are compatible here as well.

Palladium-Catalyzed Perfluoroalkylative Carbonylation of Unactivated Alkenes: Access to ß-Perfluoroalkyl Esters.

Transition-metal-catalyzed multi-component carbonylation represents an efficient strategy for the preparation of various functionalized carbonyl-containing compounds. Herein, we report a general palladium-catalyzed perfluoroalkylative carbonylation of unactivated alkenes using inexpensive and readily available carbon monoxide as the C1 source and perfluoroalkyl halides as the coupling partner. A wide range of phenols and alcohols were transformed into the corresponding ß-perfluoroalkyl esters in high yields with broad functional group tolerance and good chemoselectivity. Additionally, alkyl halides can be utilized as alkoxy source as well to give the desired esters. Moreover, several pharmaceutical and bio-active molecules were also suitable substrates for this one-pot multi-component carbonylation process to give the targeted products in good yields.

Iron-catalyzed carbonylative cyclization of γ,δ-unsaturated aromatic oxime esters with amines.

An efficient iron-catalyzed carbonylative cyclization of γ,δ-unsaturated aromatic oxime esters with amines has been developed. A range of functionalized ß-homoproline amide derivatives were prepared via an iminyl radical-mediated intramolecular 1,5-cyclization followed by carbon radical-triggered intermolecular carbonylation. Examples on further transforming the obtained product were successfully discussed as well.

Rhodium-Catalyzed Carbonylative Synthesis of Aryl Salicylates from Unactivated Phenols.

A rhodium-catalyzed carbonylative transformation of unactivated phenols to aryl salicylates is described. This protocol is characterized by utilizing 1,3-rhodium migration as the key step to provide direct access to synthesize o-hydroxyaryl esters. Various desired aryl o-hydroxybenzoates were produced in moderate to excellent yields with bis(dicyclohexylphosphino)ethane (DCPE) as the ligand. Interestingly, diphenyl carbonate was formed as the main product when 1,3-bis(diphenylphosphino)propane (DPPP) was used as the ligand. A plausible reaction mechanism is proposed.

Iron-catalyzed carbonylative cyclization of γ,δ-unsaturated aromatic oxime esters to functionalized pyrrolines.

Herein, a new method of iron-catalyzed carbonylative cyclization of γ,δ-unsaturated aromatic oxime esters to functionalized pyrrolines has been developed. By using readily available substrates, 32 examples of functionalized pyrrolines were prepared in moderate to good yields. Notably, examples of reduction and cycloaddition reactions of the obtained product were given as well.

Pd/C-Catalyzed Carbonylative Synthesis of α-Carbonyl-α'-Amide Sulfoxonium Ylides from Azides.

The synthesis of α-carbonyl-α'-amide sulfoxonium ylides by Pd/C-catalyzed carbonylative transformation of azides with α-carbonyl sulfoxonium ylides has been studied. This method offers a direct approach to produce synthetically useful α-carbonyl-α'-amide sulfoxonium ylides in high efficiency. By using readily available substrates, 39 examples of products were prepared in good yields with outstanding functional group compatibility. An example of converting the obtained ylide into the corresponding 1,3-dicarbonyl compound has been given as well.

Copper-Catalyzed Carbonylative Synthesis of ß-Homoprolines from N-Fluoro-sulfonamides.

A new methodology for the carbonylative transformation of N-fluoro-sulfonamides into N-sulfonyl-ß-homoproline esters has been described. In the presence of a catalytic amount of Cu(OTf)2, a range of ß-homoproline derivatives were prepared in moderate to good yield. The reaction proceeds via the intramolecular cyclization and intermolecular carbonylation of a free carbon radical. Notably, this procedure offers the possibility to build potential functionalized bioactive molecules.

The Exploration of Aroyltrimethylgermane as Potent Synthetic Origins and Their Preparation.

The synthetic utilities of acylgermanes are surprisingly rarely explored compared with their analogues. In this communication, the survey of aroyltrimethylgermane as potent synthetic origins has been studied. A variety of novel chemical transformations have been realized, including using the acylgermane group as a directing group in Rh-catalyzed aromatic C-H alkenylation reaction and Ir-catalyzed aromatic C-H amidation reactions. Additionally, a general approach for acylgermanes preparation has been established as well. The catalytic system proceeds effectively in the presence of Pd(OAc)2/BINOL-based monophosphite (L11) and allows for the straightforward access to a wide range of functionalized acylgermanes in high yields.

Association of total oxidant status, total antioxidant status, and malondialdehyde and catalase levels with psoriasis: a systematic review and meta-analysis.

Although oxidative stress plays a major role in psoriasis, the association between oxidative stress biomarker levels and psoriasis in humans remains controversial. Relevant articles were retrieved by searching the following databases: PubMed, Web of Science, and EMBASE, without any time limit (updated March 10th, 2019). The pooled weighted mean difference (WMD) and 95% confidence interval (CI) for the total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), and catalase (CAT) were calculated for each study. Heterogeneity test, publication bias analysis, and sensitivity analysis were performed. A total of 28 case-control studies, containing a combined total of 2724 subjects (1485 psoriasis patients and 1239 healthy controls), were enrolled in this meta-analysis. The combined results showed a significant difference in the TAS levels (WMD = - 0.213 mmol/L, p < 0.001, 95% CI = - 0.216 to - 0.165), TOS levels (WMD = 2.196 µmol/L, p < 0.001, 95% CI = 1.667 to 2.726), MDA levels (WMD = 1.854 nmol/L, p < 0.001, 95% CI = 1.494 to 2.215), and CAT levels (WMD = - 22.341 kU/L, p = 0.008, 95% CI = - 38.934 to - 5.748) between psoriasis patients and controls. Moreover, the combined results showed a significant difference in the TAS, MDA, and CAT levels in patients with mild vs. moderate psoriasis and moderate vs. severe psoriasis. TAS and CAT levels in psoriasis patients were significantly lower than in healthy controls, whereas the TOS and MDA levels were significantly higher. Furthermore, the TAS, MDA, and CAT levels are associated with the severity of disease. These results indicate that redox imbalances play a major role in the pathogenesis of psoriasis.

Carbonylation of tertiary carbon radicals: synthesis of lactams.

Herein, we disclose an interesting iron-catalyzed approach for the carbonylation of a tertiary carbon radical. The tertiary carbon radical generated from a 1,5-hydrogen atom transfer can be captured by CO gas smoothly. Various six-membered lactams were constructed chemo-selectively in high yields.

Pd/C-Catalyzed Carbonylative Synthesis of 2-Aminobenzoxazinones from 2-Iodoaryl Azides and Amines.

A palladium-catalyzed carbonylative procedure for the synthesis of 2-aminobenzoxazinones from 1-azido-2-iodobenzenes and amines has been developed. A broad range of 2-aminobenzoxazinone derivatives were prepared in moderate to excellent yields by using Pd/C as the catalyst under CO atmosphere. Notably, by using organic azides as the substrates, external oxidant usage can be successfully avoided and only forms N2 as the byproduct.

Study on the Fluorescent Activity of N²-Indolyl-1,2,3-triazole.

A new type of blue emitter, N²-Indolyl-1,2,3-triazoles (NITs), with the λmax ranging from 420-480 nm and the Stokes shift from 89-143 nm, were synthesized through the coupling reaction of indoles with triazole derivatives. The influence of different substitution patterns on the optical properties (efficiency, excitation, and emission wavelengths) of the NITs was investigated. In addition, one palladium complex were synthesized by using NITs as the ligands, which, however, exhibited no fluorescent activity, but did show the enhanced co-planarity. Lastly, two bio-active molecule derivatives were explored for the potential use of these novel dyes in related chemical and biological applications.