Friedel-Crafts-Type Arylation Strategy for the Conversion of Alkyl 2-((Diphenoxyphosphoryl)oxy)-2-arylacetates to α,α-Diaryl Esters.

An arylation strategy allowing the conversion of alkyl 2-((diphenoxyphosphoryl)oxy)-2-arylacetates to α,α-diaryl esters is reported. This transformation can be promoted by TfOH when the starting organic phosphates do not carry para-alkoxy groups on their aryl rings, but it does not require any additives when such groups are present. These alkyl 2-((diphenoxyphosphoryl)oxy)-2-arylacetates can be readily accessed from the insertion of diphenyl phosphate into aryldiazoacetates.

An aza-Robinson Annulation Strategy for the Synthesis of Fused Bicyclic Amides: Synthesis of (±)-Coniceine and Quinolizidine.

An aza-Robinson annulation strategy is described using a NaOEt-catalyzed conjugate addition of cyclic imides onto vinyl ketones, followed by a TfOH-mediated intramolecular aldol condensation to afford densely functionalized fused bicyclic amides. The potential use of these amides in the synthesis of alkaloids is demonstrated by the sequential conversion of appropriate precursors to (±)-coniceine and quinolizidine in two additional steps, thus allowing their preparation in overall 40 and 44% yields, respectively.

Visible light-mediated photolysis of organic molecules: the case study of diazo compounds.

Considering the recent rapid advancement of synthetic technologies promoted by visible light in the last 15 years, the use of photocatalysts has been rightfully justified based on the fact that organic molecules generally do not absorb visible light. However, an increasing number of different classes of organic molecules is being identified as actually directly absorbing in this region of the electromagnetic spectrum. Among them, diazo compounds are possibly one of these classes whose chemistry has been more explored so far. Indeed, irradiation of these compounds with visible light has been introduced as a mild photolytic strategy generally leading to free carbene intermediates. This strategy not only allows for a more cost-economical approach revealing similar outcomes to some previously reported thermal, metal-catalyzed transformations; but it can also eventually lead to different reactivities. Herein, we will present the contributions of our laboratory and of other groups to this research area, along with some important elements of design behind the development of selected reaction profiles, aiming to provide the reader with an overall view of the current state of the art.

Synthesis of 4-(organoselenyl) oxazolones via cyclization of N-alkynyl ethylcarbamates promoted by organoselenium.

Organoselenyl iodide promoted the intramolecular nucleophilic cyclization of N-alkynyl ethylcarbamates in the synthesis of 4-(organoselenyl) oxazolones. The reaction was regioselective, giving the five-membered oxazolone products as the unique regioisomer via an initial activation of the carbon-carbon triple bond through a seleniranium intermediate, followed by an intramolecular 5-endo-dig cyclization mode. The generality of the methodology has been proven by applying the optimized reaction conditions to different organoselenyl iodides and N-alkynyl ethylcarbamates having different substituents directly bonded to the nitrogen atom and in the terminal position of the alkyne.

Palladium-Catalyzed Cascade 5-endo-dig Cyclization of Ynamides to Form 4-Alkynyloxazolones.

The selective synthesis of 4-alkynyloxazolones and their further applications as substrates to electrophile-promoted nucleophilic cyclization have been developed. The reaction of ynamides with terminal alkynes proceeded smoothly to give 4-alkynyloxazolones in the presence of a catalytic amount of palladium(II) acetate. The products were obtained with the sequential formation of new C-C and C-O bonds via a cascade procedure. The first step involved a carbon-oxygen bond formation, via a 5-endo-dig closure, which was confirmed by X-ray analyses of the crystalline sample. Subsequently, the reaction of 4-alkynyloxazolones with an electrophilic selenium source gave 3-phenylselanyl benzofuran derivatives via an electrophile-promoted nucleophilic cyclization.

Diorganyl Diselenides and Iron(III) Chloride Drive the Regio- and Stereoselectivity in the Selenation of Ynamides.

We report here our results on the application of ynamides as substrates in the reactions with diorganyl dichalcogenides and iron(III) chloride to give selectively three different types of compounds: E-α-chloro-ß-(organoselenyl)enamides, 4-(organochalcogenyl)oxazolones, and vinyl tosylates. The results reveal that the selectivity in the formation of products was obtained by controlling the functional groups directly bonded to the nitrogen atom of the ynamides. Thus, α-chloro-ß-(organoselenyl) enamide derivatives were exclusively obtained when the TsN- and MsN-ynamides were treated with a mixture of diorganyl diselenides (1.0 equiv) and FeCl3 (3.0 equiv) in dichloroethane (DCE, 3 mL), at room temperature. The 4-(organochalcogenyl)oxazolones were selectively obtained with ynamides having an ester group, directly bonded to the nitrogen atom, upon treatment with a solution of FeCl3 (1.5 equiv) and diorganyl dichalcogenides (1.0 equiv) in dichloromethane (3 mL) at room temperature. Finally, vinyl tosylates were obtained from ynamides having an ester group, directly bonded to the nitrogen atom, by reaction with p-toluenesulfonic acid. We also studied the application of the prepared compounds as substrates for Suzuki and Sonogashira cross-coupling reactions.

Similar hepatoprotective effectiveness of Diphenyl diselenide and Ebselen against cisplatin-induced disruption of metabolic homeostasis and redox balance in juvenile rats.

Cisplatin is an antineoplastic drug well recognized for its success in the battle against several types of cancer in adult, juvenile, and child populations. Meanwhile, this drug is also famous due to its serious side effects, such as hepatotoxicity. This study evaluated the hepatoprotective effectiveness of Diphenyl Diselenide (PhSe)2 and Ebselen in a model of cisplatin-induced toxicity in juvenile rats. Juvenile Wistar rats received a single intraperitoneal (i.p) injection of cisplatin (6 mg/kg) or saline solution, at postnatal day (PND) 21. Ebselen (11 mg/kg) or (PhSe)2 (12 mg/kg) was intragastrically (i.g) administered in rats from PND 21 to PND 25. At PND 26, the blood and liver were collected for the biochemistry assays. A single administration of cisplatin was enough to alter the makers of hepatic function (an increase of AST activity) and the blood lipid profile (an increase of cholesterol and triglycerides, TG). The cisplatin-induced metabolic disruption was demonstrated by the increase of hepatic glycogen and TG contents and hexokinase, glucose-6-phosphatase, and tyrosine aminotransferase activities; a decrease of citrate synthase activity and the levels of GLUT-2. Cisplatin-induced hepatic oxidative stress was characterized by an increase in reactive oxygen species, TBARS, protein carbonyl, and Nox levels as well as the decrease in NPSH levels. Ebselen and (PhSe)2 were effective against all alterations caused by this chemotherapy medication. The present findings highlight the (PhSe)2 and Ebselen similar hepatoprotective effectiveness against cisplatin-induced disruption of metabolic homeostasis and redox balance in juvenile rats.

Cyclization of Thiopropargyl Benzimidazoles by Combining Iron(III) Chloride and Diorganyl Diselenides.

A practical synthetic approach to the synthesis of 3-(organoselenyl)-imidazothiazines was developed. The methodology involved the regioselective 6-endo-dig cyclization of thiopropargyl benzimidazoles promoted by diorganyl diselenides and iron(III) chloride. The investigation to determine the best reaction conditions indicated the use of thiopropargyl benzimidazoles (0.25 mmol) with diorganyl diselenides (1.0 equiv) and iron(III) chloride (2.0 equiv) in dichloromethane at 40 °C for 30 min to be optimal. Under these conditions, the scope of the substrates was evaluated varying the structures of thiopropargyl benzimidazoles and diorganyl diselenides giving 28 3-(organoselenyl)-imidazothiazines in moderate to good yields. The reaction conditions were also applicable to diorganyl ditellurides; however, they did not work for diorganyl disulfides. The mechanism studies were carried out indicating that the cyclization proceeds via a cooperative action of diorganyl diselenides and iron(III) chloride, but a direct electrophilic cyclization, promoted by the in situ formed electrophilic organoselenium species, cannot be ruled out.

Iron(III) chloride and diorganyl diselenides-mediated 6-endo-dig cyclization of arylpropiolates and arylpropiolamides leading to 3-organoselenyl-2H-coumarins and 3-organoselenyl-quinolinones.

Combination of iron(III) chloride and diorganyl diselenides was used for cyclization of arylpropiolates and arylpropiolamides in formation of 3-organoselenyl-2H-coumarins and 3-organoselenyl-quinolinones, respectively. Systematic study to determine the ideal conditions revealed that the two substrates reacted in the same way using identical reaction conditions. The versatility of this method has been demonstrated by extension of the best reaction conditions to substrate having a variety of substituents. Analyses of the optimization reaction also showed that diorganyl diselenides have a dual role by acting as cycling agent and base to restore the aromatic system. Mechanistic investigation studies and analyses of the products obtained have revealed that the cyclization reactions follow an initial 6-endo-dig process to give the six-membered heterocycles without involving an intramolecular ipso-cyclization route.

Synthesis of pyridazinones through the copper(I)-catalyzed multicomponent reaction of aldehydes, hydrazines, and alkynylesters.

The copper-catalyzed multicomponent cyclization reaction, which combined aldehydes, hydrazines, and alkynylesters, was applied in the synthesis of pyridazinones. The reaction was regioselective and gave only six-membered pyridazinones in the complete absence of five-membered pyrazoles or a regioisomeric mixture. During this investigation, the use of 2-halobenzaldehyde as the starting material, under identical reaction conditions, gave 6-(2-ethoxyphenyl)pyridazinones after sequential Michael addition/1,2-addition/Ullmann cross-coupling reactions.