Visible-light-mediated Regioselective Synthesis of Novel Thiazolo[3,2-b][1,2,4]triazoles: Advantageous Synthetic Application of Aqueous Conditions

From a green chemistry perspective, sustainable irradiations as the power source and water as solvent have certainly grabbed the attention of chemists in recent times as these efforts reduce hazardous...

Synthesis of Anti-Inflammatory Spirostene-Pyrazole Conjugates by a Consecutive Multicomponent Reaction of Diosgenin with Oxalyl Chloride, Arylalkynes and Hydrazines or Hydrazones

Steroid sapogenin diosgenin is of significant interest due to its biological activity and synthetic application. A consecutive one-pot reaction of diosgenin, oxalyl chloride, arylacetylenes, and phenylhydrazine give rise to steroidal 1,3,5-trisubstituted pyrazoles (isolated yield 46–60%) when the Stephens–Castro reaction and heterocyclization steps were carried out by heating in benzene. When the cyclization step of alkyndione with phenylhydrazine was performed in 2-methoxyethanol at room temperature, steroidal α,β-alkynyl (E)- and (Z)-hydrazones were isolated along with 1,3,5-trisubstituted pyrazole and the isomeric 2,3,5-trisubstituted pyrazole. The consecutive reaction of diosgenin, oxalyl chloride, phenylacetylene and benzoic acid hydrazides efficiently forms steroidal 1-benzoyl-5-hydroxy-3-phenylpyrazolines. The structure of new compounds was unambiguously corroborated by comprehensive NMR spectroscopy, mass-spectrometry, and X-ray structure analyses. Performing the heterocyclization step of ynedione with hydrazine monohydrate in 2-methoxyethanol allowed the synthesis of 5-phenyl substituted steroidal pyrazole, which was found to exhibit high anti-inflammatory activity, comparable to that of diclofenac sodium, a commercial pain reliever. It was shown by molecular docking that the new derivatives are incorporated into the binding site of the protein Keap1 Kelch-domain by their alkynylhydrazone or pyrazole substituent with the formation of more non-covalent bonds and have higher affinity than the initial spirostene core.

Visible Light Promoted Metal Free Sustainable Reduction of Activated Carbon-Carbon Double Bonds Without Any External Reductant

Visible light promoted chemo-selective metal free hydrogenation of activated double bond has been achieved via photoredox catalysis. Eosin Y has proved to an efficient catalyst for the effective reduction of C-C double bonds of isatins, oxindoles and maleimides under visible light. The method worked efficiently without the aid of any external reductants. Commercially viable DIPEA has been employed as a sacrificial electron donor and it’s in-situ generated cationic radical acts as reductant in this transformation. The method proved to be practical as a broad range of substrates containing activated double bond were easily reduced. The method proved to be scalable on a gram scale and the reduced product has been utilized successfully for the further synthetic application. The systematic and detailed mechanistic studies reveal the reductive quenching of the photocatalyst by the activated double bond.

Synthetic exploration of sulfinyl radicals using sulfinyl sulfones

Sulfinyl radicals – one of the fundamental classes of S-centered radicals – have eluded synthetic application in organic chemistry for over 60 years, despite their potential to assemble valuable sulfoxide compounds. Here we report the successful generation and use of sulfinyl radicals in a dual radical addition/radical coupling with unsaturated hydrocarbons, where readily-accessed sulfinyl sulfones serve as the sulfinyl radical precursor. The strategy provides an entry to a variety of previously inaccessible linear and cyclic disulfurized adducts in a single step, and demonstrates tolerance to an extensive range of hydrocarbons and functional groups. Experimental and theoretical mechanistic investigations suggest that these reactions proceed through sequential sulfonyl and sulfinyl radical addition.

2-Aryl-6-Polyfluoroalkyl-4-Pyrones as Promising RF-Building-Blocks: Synthesis and Application for Construction of Fluorinated Azaheterocycles

A convenient and general method for the direct synthesis of 2-aryl-6-(trifluoromethyl)-4-pyrones and 2-aryl-5-bromo-6-(trifluoromethyl)-4-pyrones has been developed on the basis of one-pot oxidative cyclization of (E)-6-aryl-1,1,1-trifluorohex-5-ene-2,4-diones via a bromination/dehydrobromination approach. This strategy was also applied for the preparation of 2-phenyl-6-polyfluoroalkyl-4-pyrones and their 5-bromo derivatives. Conditions of chemoselective enediones bromination were found and the key intermediates of the cyclization of bromo-derivatives to 4-pyrones were characterized. Synthetic application of the prepared 4-pyrones has been demonstrated for the construction of biologically important CF3-bearing azaheterocycles, such as pyrazoles, pyridones, and triazoles.

Transition-Metal-Free [3+2] Dehydration Cycloaddition of Donor-Acceptor Cyclopropanes With 2-Naphthols

A Brønsted acid-catalyzed domino ring-opening cyclization transformation of donor-acceptor (D-A) cyclopropanes and 2-naphthols has been developed. This formal [3+2] cyclization reaction provided novel and efficient access to the naphthalene-fused cyclopentanes in the absence of any transition-metal catalysts or additives. This robust procedure was completed smoothly on a gram-scale to afford the corresponding product with comparable efficiency. Furthermore, the synthetic application of the prepared product has been demonstrated by its transformation into a variety of synthetically useful molecules.

Synthetic applications of monofluoromethylsulfonium salts

Monofluoromethylsulfonium salts are emerging reagents for the fluoromethylation and fluoromethylenation or fluorometyhlene transfer. This type of reagents display simple approach for introduction of fluoromethyl group into wide range of nucleophiles upon mild basic conditions. Recently, fluoromethylsulfonium salts have been demonstrated to act as a synthetic equivalent of otherwise challenging fluoromethylene synthon. For instance, these reagents can be used for the direct synthesis of monofluoroepoxides and fluorocyclopropanes from activated alkenes via sulfur fluoromethylide intermediate. Sulfonium salts are an alternative, easy-to-handle option to volatile and environmentally concerning freons for achieving monofluorinated compounds. This review focuses on synthetic application of these reagents known to date.

Preparation and Synthetic Application of Naproxen-Containing Diaryliodonium Salts

The synthesis of naproxen-containing diaryliodonium salts has been realized from naproxen methyl ester and ArI(OH)OTs activated by trimethylsilyl trifluoromethanesulfonate (TMSOTf) in a solvent mixture comprising dichloromethane and 2,2,2-trifluoroethanol (TFE). Those iodonium salts have been successfully used in the functionalization of an aromatic ring of naproxen methyl ester, including fluorination, iodination, alkynylation, arylation, thiophenolation, and amination and esterification reactions. Moreover, further hydrolysis of the obtained 5-iodo-naproxen methyl ester afforded 5-iodo-naproxen.