Search Results (26)

Fluorinated organic molecules have become indispensable in modern chemistry, owing to the unique properties imparted by fluorine to other compounds, including enhanced metabolic stability, controlled lipophilicity, and improved bioavailability. The site-selective incorporation of fluorine atoms into organic frameworks is essential in pharmaceutical, agrochemical, and material science research. In recent years, catalytic fluorination has become an important methodology for the efficient and selective incorporation of fluorine atoms into complex molecular architectures. This review highlights advances in catalytic fluorination reactions over the past six years and describes the contributions of transition metal catalysts, photocatalysts, organocatalysts, and electrochemical systems that have enabled site-selective fluorination under a variety of conditions. Particular attention is given to the use of well-defined fluorinating agents, including Selectfluor, N-fluorobenzenesulfonimide (NFSI), AlkylFluor, Synfluor, and hypervalent iodine reagents. These reagents have been combined with diverse catalytic systems, such as AgNO₃, Rh(II), Mo-based complexes, Co(II)-salen, and various organocatalysts, including β,β-diaryl serine catalysts, isothiourea catalysts, and chiral phase-transfer catalysts. This review summarizes proposed mechanisms reported in the original studies and discusses examples of electrophilic, nucleophilic, radical, photoredox, and electrochemical fluorination pathways. Recent developments in stereoselective and more sustainable protocols are also examined. By consolidating these strategies, this article provides an up-to-date perspective on catalytic fluorination and its impact on synthetic organic chemistry. Full article

Unsymmetrical urea derivatives are essential structural motifs in a wide array of biologically significant compounds. Despite the well-established methods for synthesizing symmetrical ureas, efficient strategies for the synthesis of unsymmetrical urea derivatives remain limited. In this study, we present a novel approach for the synthesis of unsymmetrical urea derivatives through the coupling of amides and amines. Utilizing hypervalent iodine reagent PhI(OAc)₂ as a coupling mediator, this method circumvents the need for metal catalysts, high temperatures, and inert atmosphere. The reaction proceeds under mild conditions and demonstrates broad substrate scope, including various primary and secondary amines and primary benzamides. This protocol not only offers a practical and versatile route for synthesizing unsymmetrical ureas but also shows significant potential for the late-stage functionalization of complex molecules in drug development. Full article

The functionalization of unactivated substrates through the combination of copper catalysts and hypervalent iodine reagents represents a versatile tool in organic synthesis to access various classes of compounds. The hypervalent iodine derivatives can be used simply as oxidizing agents to regenerate the catalytic species or they can associate the functionalization of the starting material. In this review, special attention will be paid to methodologies which provide the introduction of nucleophiles into the reagent by use of suitable benziodoxol(on)es or iodonium salts. Many reactions concern C- and N-arylations, but may also involve formation of different carbon–carbon and carbon–nitrogen bonds, carbon–oxygen as well as carbon–halogen and carbon–phosphorus bonds. Full article

The chemistry of hypervalent iodine reagents has now become quite valuable due to the reactivity of these compounds under mild reaction conditions and their resemblance in chemical properties to transition metals. The environmentally friendly nature of these reagents makes them suitable for Green Chemistry. Reagents with a dual nature, such as iodine(III) reagents, are capable electrophiles, while iodine(V) reagents are known for their strong oxidant behavior. Various iodine(V) reagents including IBX and DMP have been used as oxidants in organic synthesis either in stoichiometric or in catalytic amounts. In this review article, we describe various oxidation reactions induced by iodine(V) reagents reported in the past decade. Full article

A shorter synthesis of the demethyl(oxy)aaptamine skeleton was developed via oxidative intramolecular cyclization of 1-(2-azidoethyl)-6-methoxyisoquinolin-7-ol followed by dehydrogenation with a hypervalent iodine reagent. This is the first example of oxidative cyclization at the ortho-position of phenol that does not involve spiro-cyclization, resulting in the improved total synthesis of 3-(phenethylamino)demethyl(oxy)aaptamine, a potent anti-dormant mycobacterial agent. Full article

Hypervalent iodine reagents are in high current demand due to their exceptional reactivity in oxidative transformations, as well as in diverse umpolung functionalization reactions. Cyclic hypervalent iodine compounds, known under the general name of benziodoxoles, possess improved thermal stability and synthetic versatility in comparison with their acyclic analogs. Aryl-, alkenyl-, and alkynylbenziodoxoles have recently received wide synthetic applications as efficient reagents for direct arylation, alkenylation, and alkynylation under mild reaction conditions, including transition metal-free conditions as well as photoredox and transition metal catalysis. Using these reagents, a plethora of valuable, hard-to-reach, and structurally diverse complex products can be synthesized by convenient procedures. The review covers the main aspects of the chemistry of benziodoxole-based aryl-, alkynyl-, and alkenyl- transfer reagents, including preparation and synthetic applications. Full article

The development of NH transfer reactions using hypervalent iodine and simple sources of ammonia has facilitated the synthesis of sulfoximines and sulfonimidamides for applications across the chemical sciences. Perhaps most notably, the methods have been widely applied in medicinal chemistry and in the preparation of biologically active compounds, including in the large-scale preparation of an API intermediate. This review provides an overview of the development of these synthetic methods involving an intermediate iodonitrene since our initial report in 2016 on the conversion of sulfoxides into sulfoximines. This review covers the NH transfer to sulfoxides and sulfinamides, and the simultaneous NH/O transfer to sulfides and sulfenamides to form sulfoximines and sulfonimidamides, respectively. The mechanism of the reactions and the identification of key intermediates are discussed. Developments in the choice of reagents, and in the reaction conditions and setups used are described. Full article

Quinones and quinols are secondary metabolites of higher plants that are associated with many biological activities. The oxidative dearomatization of phenols induced by hypervalent iodine(III) reagents has proven to be a very useful synthetic approach for the preparation of these compounds, which are also widely used in organic synthesis and medicinal chemistry. Starting from several substituted phenols and naphthols, a series of cyclohexadienone and naphthoquinone derivatives were synthesized using different hypervalent iodine(III) reagents and evaluated for their in vitro antiprotozoal activity. Antiprotozoal activity was assessed against Plasmodium falciparum NF54 and Trypanosoma brucei rhodesiense STIB900. Cytotoxicity of all compounds towards L6 cells was evaluated and the respective selectivity indices (SI) were calculated. We found that benzyl naphthoquinone 5c was the most active and selective molecule against T. brucei rhodesiense (IC₅₀ = 0.08 μM, SI = 275). Furthermore, the antiprotozoal assays revealed no specific effects. In addition, some key physicochemical parameters of the synthesised compounds were calculated. Full article

The chemistry of polyvalent iodine compounds has piqued the interest of researchers due to their role as important and flexible reagents in synthetic organic chemistry, resulting in a broad variety of useful organic molecules. These chemicals have potential uses in various functionalization procedures due to their non-toxic and environmentally friendly properties. As they are also strong electrophiles and potent oxidizing agents, the use of hypervalent iodine reagents in palladium-catalyzed transformations has received a lot of attention in recent years. Extensive research has been conducted on the subject of C—H bond functionalization by Pd catalysis with hypervalent iodine reagents as oxidants. Furthermore, the iodine(III) reagent is now often used as an arylating agent in Pd-catalyzed C—H arylation or Heck-type cross-coupling processes. In this article, the recent advances in palladium-catalyzed oxidative cross-coupling reactions employing hypervalent iodine reagents are reviewed in detail. Full article

Hypervalent iodine heterocycles represent one of the important classes of hypervalent iodine reagents with many applications in organic synthesis. This paper reports a simple and convenient synthesis of benziodazolones by the reaction of readily available iodobenzamides with m-chloroperoxybenzoic acid in acetonitrile at room temperature. The structure of one of these new iodine heterocycles was confirmed by X-ray analysis. In combination with PPh₃ and pyridine, these benziodazolones can smoothly react with alcohols or amines to produce the corresponding esters or amides of 3-chlorobenzoic acid, respectively. It was found that the novel benziodazolone reagent reacts more efficiently than the analogous benziodoxolone reagent in this esterification. Full article

This study may open a new way to obtain the coloration of a polymer during functionalization. Two polyacrylonitrile (PAN) polymers in the form of textile fibers (Melana and Dralon L) were subjected to functionalization treatments in order to improve the dyeing capacity. The functionalizations determined by an organo-hypervalent iodine reagent developed in situ led to fiber coloration without using dyes. KIO₃ was formed in situ from the interaction of aqueous solutions of 3–9% KOH with 3–9% I₂, at 120 °C. The yellow-orange coloration appeared as a result of the transformations in the chemical structure of each functionalized polymer, with the formation of iodinehydrin groups. The degree of functionalization directly influenced the obtained color. The results of the Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), Map and Temogravimetric Analysis (TG) plus Differential Thermal (DTA) analyses indicated the presence of new functional groups, such as iodine-oxime. The X-ray diffraction (XRD) analysis confirmed the change of the crystalline/amorphous ratio in favor of the former. The new groups introduced by functionalization make it possible to dye with classes of dyes specific to these groups, but not specific to PAN fibers, thus improving their dyeing capacity. Full article

We report a convenient and practical method for the preparation of nonexplosive cyclic hypervalent iodine(III) oxidants as efficient organocatalysts and reagents for various reactions using Oxone^® in aqueous solution under mild conditions at room temperature. The thus obtained 2-iodosobenzoic acids (IBAs) could be used as precursors of other cyclic organoiodine(III) derivatives by the solvolytic derivatization of the hydroxy group under mild conditions of 80 °C or lower temperature. These sequential procedures are highly reliable to selectively afford cyclic hypervalent iodine compounds in excellent yields without contamination by hazardous pentavalent iodine(III) compound. Full article

Oxidative fragmentation of tertiary cyclopropanols with phenyliodine(III) dicarboxylates in aprotic solvents (dichloromethane, chloroform, toluene) produces mixed anhydrides. The fragmentation reaction is especially facile with phenyliodine(III) reagents bearing electron-withdrawing carboxylate ligands (trifluoroacetyl, 2,4,6-trichlorobenzoyl, 3-nitrobenzoyl), and affords 95−98% yields of the corresponding mixed anhydride products. The latter can be straightforwardly applied for the acylation of various nitrogen, oxygen and sulfur-centered nucleophiles (primary and secondary amines, hydroxylamines, primary alcohols, phenols, thiols). Intramolecular acylation yielding macrocyclic lactones can also be performed. The developed transformation has bolstered the synthetic utility of cyclopropanols as pluripotent intermediates in diversity-oriented synthesis of bioactive natural products and their synthetic congeners. For example, it was successfully applied for the last-stage modification of a cyclic peptide to produce a precursor of a known histone deacetylase inhibitor. Full article

The occurrence of phenanthrenes is limited in nature, with such compounds identified only in some plant families. Phenanthrenes were described to have a wide range of pharmacological activities, and numerous research programs have targeted semisynthetic derivatives of the phenanthrene skeleton. The aims of this study were the phytochemical investigation of Juncus tenuis, focusing on the isolation of phenanthrenes, and the preparation of semisynthetic derivatives of the isolated compounds. From the methanolic extract of J. tenuis, three phenanthrenes (juncusol, effusol, and 2,7-dihydroxy-1,8-dimethyl-5-vinyl-9,10-dihydrophenanthrene) were isolated. Juncusol and effusol were transformed by hypervalent iodine(III) reagent, using a diversity-oriented approach. Four racemic semisynthetic compounds possessing an alkyl-substituted p-quinol ring (1–4) were produced. Isolation and purification of the compounds were carried out by different chromatographic techniques, and their structures were elucidated by means of 1D and 2D NMR, and HRMS spectroscopic methods. The isolated secondary metabolites and their semisynthetic analogues were tested on seven human tumor cell lines (A2780, A2780cis, KCR, MCF-7, HeLa, HTB-26, and T47D) and on one normal cell line (MRC-5), using the MTT assay. The effusol derivative 3, substituted with two methoxy groups, showed promising antiproliferative activity on MCF-7, T47D, and A2780 cell lines with IC₅₀ values of 5.8, 7.0, and 8.6 µM, respectively. Full article

This review article focused on the innovative procedure for electrophilic fluorination using HF and in situ generation of the required electrophilic species derived from hypervalent iodine compounds. The areas of synthetic application of this approach include fluorination of 1,3-dicarbonyl compounds, aryl-alkyl ketones, styrene derivatives, α,β-unsaturated ketones and alcohols, homoallyl amine and homoallyl alcohol derivatives, 3-butenoic acids and alkynes. Full article