Hydroxytrifluoroethylation and Trifluoroacetylation Reactions via SET Processes.

Hydroxytrifluoroethyl and trifluoroacetyl groups are of utmost importance in biologically active compounds, but methods to tether these motifs to organic architectures have been limited. Typically, the preparation of these compounds relied on the use of strong bases or multistep routes. The renaissance of radical chemistry in photocatalytic, transition metal mediated, and hydrogen atom transfer (HAT) processes have allowed the installation of these medicinally relevant fluorinated motifs. This review provides an overview of the methods available for the direct synthesis of hydroxytrifluoroethyl- and trifluoroacetyl-derived compounds governed by single-electron transfer processes.

Difluoroalkylation of Anilines via Photoinduced Methods.

The development of sustainable and mild protocols for the fluoroalkylation of organic backbones is of current interest in chemical organic synthesis. Herein, we present operationally simple and practical transition-metal-free methods for the preparation of difluoroalkyl anilines. First, a visible-light organophotocatalytic system working via oxidative quenching is described, providing access to a wide range of difluoroalkyl anilines under mild conditions. In addition, the formation of an unprecedented electron donor-acceptor (EDA) complex between anilines and ethyl difluoroiodoacetate is reported and exploited as an alternative, efficient, and straightforward strategy to prepare difluoroalkyl derivatives.

Recent Advances on Antimicrobial and Anti-Inflammatory Cotton Fabrics Containing Nanostructures.

Hydrophilic cotton textiles, used in hospitals and sportswear, are prone to the growth of microorganisms (bacteria, fungi) resulting in hygiene and health risks. Thus, healthcare concerns have motivated the interest for the development of multifunctional antimicrobial cotton fabrics. Moreover, cotton textiles are also used in medical applications such as wound dressings. Their functionalization with anti-inflammatory agents is desirable in order to accelerate cicatrisation in the treatment of chronic wounds. This review summarizes recent advances (from January 2016 to January 2021) on the modification and coating of cotton fabrics with nanostructures (mainly metal and metal oxide nanoparticles, functionalized silica nanoparticles) to provide them antimicrobial (antibacterial and antifungal) and anti-inflammatory properties.

Biotinylated Phosphorus Dendrimers as Control Line in Nucleic Acid Lateral Flow Tests.

Lateral flow assays (LFA) are an affordable, easy-to-use, qualitative rapid test for clinical diagnosis in nonlaboratory environments and low-resource facilities. The control line of these tests is very important to provide a valid result, confirming that the platform operates correctly. A clear, nondiffused line is desirable. The number of colored nanoparticles that reach the control line in a positive test can be very small, and they should all be trapped efficiently by the molecules adsorbed there. In this work, we proposed the use of robust biotinylated dendrimers of two different generations as signal amplifiers in control lines of LFA, able to react with streptavidin-modified gold nanoparticles. Besides the synthesis and characterization, the analytical performance as control lines will be studied, and their response will be compared with other commercially available biotinylated molecules. Finally, the utility of the dendrimer implemented in a NALF (Nucleic Acid Lateral Flow) strip was also demonstrated for detection of the amplicons obtained by double-tagging PCR (polymerase chain reaction) for the detection of E. coli as a model of foodborne pathogen.

Enantioenriched Quaternary α-Pentafluoroethyl Derivatives of Alkyl 1-Indanone-2-Carboxylates.

An electrophilic enantioselective catalytic method for the α-pentafluoroethylation of 3-oxoesters is described. Under the use of La(OTf)3 in combination with a (S,R)-indanyl-pybox ligand, good results in terms of yield and enantioselectivities were achieved (up to 89% ee). The reaction proceeds under mild conditions, leading to the formation of enantioenriched quaternary centers. This methodology uses an hypervalent iodine(III)-CF2CF3 reagent, and mechanistic investigations are consistent with the involvement of a radical pathway.

Stepwise Mechanism for the Bromination of Arenes by a Hypervalent Iodine Reagent.

A mild, metal-free bromination method of arenes has been developed using the combination of bis(trifluoroacetoxy)iodobencene and trimethylsilyl bromide. In situ-formed dibromo(phenyl)-λ3-iodane (PhIBr2) is proposed as the reactive intermediate. This methodology using PIFA/TMSBr has been applied with success to a great number of substrates (25 examples). The treatment of mono-substituted activated arenes led to para-brominated products (2u-z) in excellent 83-96% yields. Density functional theory calculations indicate a stepwise mechanism involving a double bromine addition followed by a type II dyotropic reaction with concomitant re-aromatization of the six-membered ring.

Asymmetric Preparation of α-Quaternary Fluorinated ß-keto Esters. Review.

In this review, recent advances over the past decade in the preparation of fluorinated stereogenic quaternary centers on ß-keto esters compounds are analyzed. Since the incorporation of fluorine and fluorinated groups is of special interest in pharmaceutical chemistry, a range of metal-catalyzed and organocatalyzed methods have been developed. Herein, we review the enantioselective fluorination, trifluoromethylation and trifluoromethylthiolation of 3-oxo esters. The scope, the induction of enantioselectivity and mechanistic investigations are presented.

Lanthanum-Catalyzed Enantioselective Trifluoromethylation by Using an Electrophilic Hypervalent Iodine Reagent.

A highly enantioselective catalytic method for the synthesis of quaternary α-trifluoromethyl derivatives of 3-oxo esters is described. The reaction uses lanthanum(III) triflate and chiral PyBOX-type C2 -symmetric ligands to generate intermediate LaIII complexes that incorporate an enolate moiety of the starting 3-oxo ester and the trifluoromethylation transfer reagent. The enantioselectivity of the reaction stems from the efficient blockage of one of the prochiral faces of the LaIII enolate by one unit of the C2 -symmetric ligand.

Catalytic Asymmetric Fluorination of Alkyl 1-indanone-2-carboxylates Ruled by Pybox-Eu(III) Combination.

A highly enantioselective catalytic method for the synthesis of quaternary α-fluoro derivatives of 3-oxo esters is described. The reaction uses europium (III) triflate and commercially available chiral pybox-type C2-symmetric ligand. Excellent results in terms of yields and enantioselectivities were assured using the electrophilic NFSI reagent under mild reaction conditions.

Fluorous l-Carbidopa Precursors: Highly Enantioselective Synthesis and Computational Prediction of Bioactivity.

New fluorous enantiopure (S)-α-aminated ß-keto esters were prepared through a highly enantioselective electrophilic α-amination step in the presence of europium triflate and (R,R)-phenyl-pybox. These compounds are precursors of fluorinated analogues of l-carbidopa, which is known to inhibit DOPA decarboxylase (DDC), a key protein in Parkinson's disease. Fluorination provides better stability for biological applications, which could possibly lead to DDC inhibitors better than l-carbidopa itself. Induced fit docking computational simulations performed on the new structures interacting with DDC highlight that for an efficient binding at the DDC site, at least one hydroxyl substituent must be present at the aromatic ring of the l-carbidopa analogues and show that the presence of fluorine can further fix the position of the ligand in the active site.

Triarylmethane Dyes for Artificial Repellent Cotton Fibers.

Families of new hydrophobic and/or oleophobic triarylmethane dyes possessing long hydrocarbon or polyfluorinated chains have been prepared. When covalently grafted on to cotton fabric, these dyes give rise to a new type of colored superhydrophobic fibers.

Acid Activation in Phenyliodine Dicarboxylates: Direct Observation, Structures, and Implications.

The use of the hypervalent iodine reagents in oxidative processes has become a staple in modern organic synthesis. Frequently, the reactivity of λ3 iodanes is further enhanced by acids (Lewis or Brønsted). The origin of such activation, however, has remained elusive. Here, we use the common combination of PhI(OAc)2 with BF3·Et2O as a model to fully explore this activation phenomenon. In addition to the spectroscopic assessment of the dynamic acid-base interaction, for the first time the putative PIDA·BF3 complex has been isolated and its structure determined by X-ray diffraction. Consequences of such activation are discussed from a structural and electronic (DFT) points of views, including the origins of the enhanced reactivity.

Ammonia Borane Dehydrogenation Promoted by a Pincer-Square-Planar Rhodium(I) Monohydride: A Stepwise Hydrogen Transfer from the Substrate to the Catalyst.

The pincer d(8)-monohydride complex RhH{xant(P(i)Pr2)2} (xant(P(i)Pr2)2 = 9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene) promotes the release of 1 equiv of hydrogen from H3BNH3 and H3BNHMe2 with TOF50% values of 3150 and 1725 h(-1), to afford [BH2NH2]n and [BH2NMe2]2 and the tandem ammonia borane dehydrogenation-cyclohexene hydrogenation. DFT calculations on the ammonia borane dehydrogenation suggest that the process takes place by means of cis-κ(2)-PP-species, through four stages including: (i) Shimoi-type coordination of ammonia borane, (ii) homolytic addition of the coordinated H-B bond to afford a five-coordinate dihydride-boryl-rhodium(III) intermediate, (iii) reductive intramolecular proton transfer from the NH3 group to one of the hydride ligands, and (iv) release of H2 from the resulting square-planar hydride dihydrogen rhodium(I) intermediate.

An alternative to the classical α-arylation: the transfer of an intact 2-iodoaryl from ArI(O2CCF3)2.

The α-arylation of carbonyl compounds is generally accomplished under basic conditions, both under metal catalysis and via aryl transfer from the diaryl λ(3)-iodanes. Here, we describe an alternative metal-free α-arylation using ArI(O2CCF3)2 as the source of a 2-iodoaryl group. The reaction is applicable to activated ketones, such as α-cyanoketones, and works with substituted aryliodanes. This formal C-H functionalization reaction is thought to proceed through a [3,3] rearrangement of an iodonium enolate. The final α-(2-iodoaryl)ketones are versatile synthetic building blocks.

Coated Cotton Fabrics with Antibacterial and Anti-Inflammatory Silica Nanoparticles for Improving Wound Healing.

Herein, we report the preparation of bifunctional silica nanoparticles by covalent attachment of both an anti-inflammatory drug (ibuprofen) and an antibiotic (levofloxacin or norfloxacin) through amide groups. We also describe the coating of cotton fabrics with silica nanoparticles containing both ibuprofen and norfloxacin moieties linked by amide groups by using a one-step coating procedure under ultrasonic conditions. The functionalized nanoparticles and cotton fabrics have been characterized using spectroscopic and microscopic techniques. The functionalized nanoparticles and textiles have been treated with model proteases for the in situ release of the drugs by the amide bond enzymatic cleavage. Topical dermal applications in medical bandages are expected, which favor wound healing.

Direct arylation of oligonaphthalenes using PIFA/BF3·Et2O: from double arylation to larger oligoarene products.

Direct dehydrogenative coupling between the linear ter- and quaternaphthalenes and substituted benzenes was achieved under the Kita conditions using the hypervalent PIFA/BF3 reagent. Products resulting from either the double arylation of the naphthalenic substrate or the formal dimerizative arylation have been prepared. For example, in the latter mode, ternaphthalene was converted into a series of linear octiarenes (counting the capping Ar). The process represents an alternative to the cross-coupling methodologies employed in related syntheses and proceeds via a selective functionalization of six relatively inert aromatic CH bonds.

Site-selective and metal-free C-H phosphonation of arenes via photoactivation of thianthrenium salts.

Aryl phosphonates are prevalent moieties in medicinal chemistry and agrochemicals. Their chemical synthesis normally relies on the use of precious metals, harsh conditions or aryl halides as substrates. Herein, we describe a sustainable light-promoted and site-selective C-H phosphonation of arenes via thianthrenation and the formation of an electron donor-acceptor complex (EDA) as key steps. The method tolerates a wide range of functional groups including biomolecules. The use of sunlight also promotes this transformation and our mechanistic investigations support a radical chain mechanism.

Direct assembly of polyarenes via C-C coupling Using PIFA/BF3·Et2O.

Direct oxidative Kita-type coupling between naphthalene and substituted benzenes was found to proceed via four-component coupling, leading to a linear tetraarene with a binaphthalene core. The methodology was extendable to the coupling of unfunctionalized 1,1'-binaphthalene with mesitylene to give a linear hexaarene product in a remarkably chemoselective manner in 87% yield. The method represents an attractive alternative to the traditional syntheses of related oligonaphthalene products via a sequence of metal-catalyzed cross-coupling steps.

Anti-inflammatory Cotton Fabrics and Silica Nanoparticles with Potential Topical Medical Applications.

The preparation of functional cotton fabrics and silica nanoparticles by direct covalent linking of nonsteroidal anti-inflammatory drugs (salicylic acid, ibuprofen, and diclofenac) through an amide group is reported. Moreover, the coating of cotton fabrics with silica nanoparticles functionalized with such antiinflamatory agents is found to increase the roughness of the surface, providing hydrophobicity to the modified fabrics. This property is enhanced by the addition of fluorinated alkyl silane in the co-condensation process to form the coating solution. Characterization of the functionalized nanoparticles and cotton textiles is accomplished by microscopic and spectroscopic techniques. The treatment of functionalized nanoparticles and cotton fabrics with model proteases and leukocytes from animal origin results in the in situ release of the drug by the selective enzymatic cleavage of the amide bond. Topical cutaneous applications in wound dressings and cream formulations for the acceleration of wound healing are envisaged.

Alkynylation of aryl halides with perfluoro-tagged palladium nanoparticles immobilized on silica gel under aerobic, copper- and phosphine-free conditions in water.

The utilization of perfluoro-tagged palladium nanoparticles immobilized on fluorous silica gel through fluorous-fluorous interactions (Pd(np)-/FSG) or linked to silica gel by covalent bonds (Pd(np)-) in the alkynylation of terminal alkynes with aryl halides under aerobic, copper- and phosphine-free conditions in water, and their recovery and re-utilization, is described.