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3,5-Diiodo-8-aryl-BODIPYs are prepared from the corresponding 3,5-dichloro- and 3,5-dibromo- congeners via a double aromatic Finkelstein reaction with NaI in refluxing propionitrile, in yields from 51 to 100%. Rate enhancement is observed for 3,5-dibromo-BODIPYs (ArBr > ArCl) suggesting a concerted SNAr mechanism for this transformation. Thus formed 3,5-diiodo-BODIPYs are examined as coupling partners in Migita-Kosugi-Stille, Mizoroki-Heck, Sonogashira, and Suzuki-Miyaura reactions, providing routes toward complex BODIPY architectures.

This communication gives an overview of the relationships between four reactions that although related were not always perceived as such: S2, Walden, Finkelstein, and Menshutkin. Binary interactions (S2 & Walden, S2 & Menshutkin, S2 & Finkelstein, Walden & Menshutkin, Walden & Finkelstein, Menshutkin & Finkelstein) were reported. Carbon, silicon, nitrogen, and phosphorus as central atoms and fluorides, chlorides, bromides, and iodides as lateral atoms were considered. Theoretical calculations provide Gibbs free energies that were analyzed with linear models to obtain the halide contributions. The M06-2x DFT computational method and the 6-311++G(d,p) basis set have been used for all atoms except for iodine where the effective core potential def2-TZVP basis set was used. Concerning the central atom pairs, carbon/silicon vs. nitrogen/phosphorus, we reported here for the first time that the effect of valence expansion was known for Si but not for P. Concerning the lateral halogen atoms, some empirical models including the interaction between F and I as entering and leaving groups explain the Gibbs free energies., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Ministerio de Ciencia, Innovación y Universidades (PGC2018-094644-B-C22), and Comunidad Autónoma de Madrid (P2018/EMT-4329 AIRTEC-CM)

Anion exchange of halide perovskite has been successfully demonstrated as an effective route to modulate its optoelectronic properties; however, it generally suffers from the issues of morphology d...

International audience; Non-symmetrical chiral 4,4′-bipyridines have recently found interest in organocatalysis and medicinal chemistry. In this regard, the development of efficient methods for their synthesis is highly desirable. Herein, a series of non-symmetrical atropisomeric polyhalogenated 4,4′-bipyridines were prepared and further functionalized by using cross-coupling reactions. The desymmetrization step is based on the N-oxidation of one of the two pyridine rings of the 4,4′-bipyridine skeleton. The main advantage of this methodology is the possible post-functionalization of the pyridine N-oxide, allowing selective introduction of chlorine, bromine or cyano groups in 2- and 2′-postions of the chiral atropisomeric 4,4′-bipyridines. The crystal packing in the solid state of some newly prepared derivatives was analyzed and revealed the importance of halogen bonds in intermolecular interactions

straightforward and practical synthesis of 2,3-diiodo-1,4-naphthoquinone is reported. Based on the prepared diiodide, a new synthetic approach to symmetric bisubstituted 1,4-naphthoquinones via double Suzuki–Miyaura reaction at room temperature has been researched and developed. The presented general method combines broad-spectrum applicability, efficiency, and simplicity providing target materials in good to quantitative yields.

New eco-friendly conditions for Finkelstein reaction employing homogeneous media or alumina-supported reagents, both solventless, were utilized in the bromohydrins and iodohydrins synthesis from 1,3-dichlorohydrin (1,3-DCH), obtained from glycerol. Thus, the trans-halogenation of glycerol-1,3-dichlorohydrin (1) in homogeneous media, using NaI, NaBr salts and organic additives (TBAI, TBAB), led to the synthesis of four different glycerol halohydrins (2a, 2b, 3a, 3b) in regular to excellent conversions (43–96%) and good selectivities to 3a and 2b. Already, the alumina-supported reagents such as KI, KBr, NaBr were used for glycerol-1,3-dichlorohydrin trans-halogenation, in the absence of solvent, producing halohydrin mixtures in high conversions (77–99%) and very good selectivity (82%) to 1,3-diiodo-2-propanol (2b).

A simple continuous flow synthesis of alkenyl chlorides from the corresponding readily available alkenyl iodides in a copper reactor tubing is described. A variety of alkenyl chlorides were obtained in good to excellent yields with full retention of the double bond geometry. The reaction time was reduced by a factor of 24 to 48 compared to the batch process., SCOPUS: ar.j, info:eu-repo/semantics/published

The 3,3&prime, 5,5&prime, tetrachloro-2-iodo-4,4&prime, bipyridine structure is proposed as a novel chemical scaffold for the design of new transthyretin (TTR) fibrillogenesis inhibitors. In the frame of a proof-of-principle exploration, four chiral 3,3&prime, tetrachloro-2-iodo-2&prime, substituted-4,4&prime, bipyridines were rationally designed and prepared from a simple trihalopyridine in three steps, including a Cu-catalysed Finkelstein reaction to introduce iodine atoms on the heteroaromatic scaffold, and a Pd-catalysed coupling reaction to install the 2&prime, substituent. The corresponding racemates, along with other five chiral 4,4&prime, bipyridines containing halogens as substituents, were enantioseparated by high-performance liquid chromatography in order to obtain pure enantiomer pairs. All stereoisomers were tested against the amyloid fibril formation (FF) of wild type (WT)-TTR and two mutant variants, V30M and Y78F, in acid mediated aggregation experiments. Among the 4,4&prime, bipyridine derivatives, interesting inhibition activity was obtained for both enantiomers of the 3,3&prime, tetrachloro-2&prime, (4-hydroxyphenyl)-2-iodo-4,4&prime, bipyridine. In silico docking studies were carried out in order to explore possible binding modes of the 4,4&prime, bipyridine derivatives into the TTR. The gained results point out the importance of the right combination of H-bond sites and the presence of iodine as halogen-bond donor. Both experimental and theoretical evidences pave the way for the utilization of the iodinated 4,4&prime, bipyridine core as template to design new promising inhibitors of TTR amyloidogenesis.

An efficient total synthesis of the chlorinated thiazole-containing natural product conulothiazole A is reported. Key features of this synthesis include a novel rhodium-catalyzed enantioselective hydrogenation of a 2-enamido-thiazole and a vinylic Finkelstein reaction that could be implemented at all stages of the synthesis to install the chlorinated alkene., SCOPUS: ar.j, info:eu-repo/semantics/published

We thank the Engineering and Physical Sciences Research Council, UK, for a research grant. The fluorinase enzyme from Streptomyces cattleya is shown to catalyse a direct displacement of bromide and iodide by fluoride ion from 5′-bromodeoxyadenosine (5′-BrDA) and 5′-iododeoxyadenosine (5′-IDA) respectively to form 5′-fluorodeoxyadenosine (5′-FDA) in the absence of L-methionine (L-Met) or S-adenosyl-L-methionine (SAM). 5′-BrDA is the most efficient substrate for this enzyme catalysed Finkelstein reaction. Postprint

An efficient and broadly applicable procedure for the copper-catalyzed vinylic Finkelstein reaction is reported. Using a simple, readily available and cheap catalytic system, a broad range of alkenyl iodides and bromides can be smoothly converted to their lower homologues with high yields and full retention of the double bond geometry. Key features of this vinylic Finkelstein reaction are its broad applicability, enabling the conversion of readily available alkenyl iodides to their less available brominated and chlorinated counterparts, and the mild reaction conditions compatible with a range of highly functionalized substrates. The potential of this vinylic halogen exchange reaction in total synthesis and medicinal chemistry was demonstrated by its successful use for the synthesis of the C1–C9 fragment of laingolide B and for the late-stage modification of drug-like molecules. The extension of this halogen exchange to the acetylenic and allenic Finkelstein reactions is also reported.

Aryl iodides play an important role in synthetic organic chemistry as they are frequently utilized in cross-coupling reactions and in oxidation processes using hypervalent iodine compounds. Their synthesis is, however, often cumbersome and may lead to unwanted side products. Here, we report on an improved protocol for the aryl Finkelstein reaction in which dehalogenation is prevented by addition of zinc iodide in lieu of copper(I). Generally, electron-poor ortho-bromo methyl benzoates, amides, and even unprotected phenols are well-suited for this method.

A pot-economical total synthesis of antifungal Sch-725674, 1, is reported. The approach takes advantage of a number of one-pot, sequential transformations, including a phosphate tether-mediated one-pot, sequential RCM/CM/chemoselective hydrogenation protocol, a one-pot tosylation/acrylation sequence, and a one-pot, sequential Finkelstein reaction/Boord olefination/acetonide deprotection procedure to streamline the synthesis route by reducing isolation and purification procedures, thus saving time. Overall, an asymmetric route has been developed that is efficiently accomplished in seven pots from phosphate (S,S)-triene and with minimal purification.

Preparative procedure for 4,5-bis(diethoxyphosphorylmethyl)-3-furoate from 4-chloromethyl-3-furoate is developed. It includes substitution of chlorine with iodine, phosphorylation by means of the Arbuzov reaction, chloromethylation of 4-(diethoxyphosphorylmethyl)-3-furoate in the position 5 of the furan ring, substitution of chlorine with iodine in the obtained chloromethyl derivative, and repeated phosphorylation with triethyl phosphite. It was found that ethyl 4-(diethoxyphosphorylmethyl)-5(chloromethyl)-3-furoate reacts with sodium diethyl phosphite by two pathways. Besides usual nucleophilic substitution leading to phosphonate, transfer of the reaction center in the position 2 of the furan ring takes place. The ambident diethylphosphite anion in this case reacts at the oxygen to give tertiary phosphite. The latter is oxidized with the air oxygen to form ethyl 2-(diethoxyphosphoryloxy)-4-(diethoxyphosphorylmethyl)-5-methyl-3-furoate. Unlike that analogous iodomethyl phosphonate is phosphorylated selectively under the conditions of the Arbuzov reaction.

The determination of Abraham descriptors for single ions is reviewed, and equations are given for the partition of single ions from water to a number of solvents. These ions include permanent anions and cations and ionic species such as carboxylic acid anions, phenoxide anions and protonated base cations. Descriptors for a large number of ions and ionic species are listed, and equations for the prediction of Abraham descriptors for ionic species are given. The application of descriptors for ions and ionic species to physicochemical processes is given; these are to water-solvent partitions, HPLC retention data, immobilised artificial membranes, the Finkelstein reaction and diffusion in water. Applications to biological processes include brain permeation, microsomal degradation of drugs, skin permeation and human intestinal absorption. The review concludes with a section on the determination of descriptors for ion-pairs.

Dehalogenation of а series substituted 2-chloroquinoline-3-carbaldehydes was investigated. It was found that zinc dust in alkali ethanol practically do not react with 2-chloro-3-(1,3-dioxolan)-2-yl-7-methylquinolines for a 5 day at ambient temperature. Increase temperature to boiling point of reaction mixture lead to increase yield 7-methylquinoline-3-carbaldehyde to 12.5%. This reaction with 2-chloro-3-dimetoxymetyl-7-methylquinoline give 26.5 above aldehyde. Replacement of ethanol to methanol give only traces of desired aldehyde. Neither 2-chloro-7-methylquinoline-3-carbaldehyde, nor his acetals do not react with sodium dithionite. Furthermore for activation of halogen we replaced chloraldehydes to iodoaldehydes by Finkelstein reaction, then protect aldehyde function by formation of dimethylacetals and treatment his by sodium dithionite in mixture pyridine-water. Desired aldehydes was obtained with poor to moderate yields. Increasing yields of this reaction is goal our further investigations.

The facile iodination of aromatic compounds under mild conditions is a great challenge for both organic and medicinal chemistry. Particularly, the synthesis of functionalized aryl iodides by light has long been considered impossible due to their photo-lability, which actually makes aryl iodides popular starting materials in many photo-substitution reactions. Herein, a photo-induced halogen exchange in aryl or vinyl halides has been discovered for the first time. A broad scope of aryl iodides can be prepared in high yields at room temperature under exceptionally mild conditions without any metal or photo-redox catalysts. The presence of a catalytic amount of elemental iodine could promote the reaction significantly.

A general, rapid, and efficient method for the copper-catalyzed Finkelstein reaction of (hetero)aromatics has been developed using continuous flow to generate a variety of aryl iodides. The described method can tolerate a broad spectrum of functional groups, including N-H and O-H groups. Additionally, in lieu of isolation, the aryl iodide solutions were used in two distinct multistep continuous-flow processes (amidation and Mg-I exchange/nucleophilic addition) to demonstrate the flexibility of this method.

The preparation of 27 isomers of chiral hexahalogeno-4,4′-bipyridines by means of two complementary methods is described. The first one is convergent and based on the LDA-induced 4,4′-dimerization of trihalopyridines, whereas the second method is divergent and achieved through regioselective halogenation reactions of 4,4′-bipyridine-2,2′-diones. Iodine in 2,2′-positions of the 4,4′-bipyridines was introduced by a copper-catalyzed Finkelstein reaction (Buchwald procedure) performed on 2,2′-dibromo derivatives. Selected compounds of this new family of atropisomeric 4,4′-bipyridines were enantioseparated by high performance liquid chromatography on chiral stationary phases, and the absolute configurations of the separated enantiomers were assigned by using X-ray diffraction analysis. The latter revealed that various halogen bond types are responsible for crystal cohesion.

Aryl iodides are superior coupling partners in cross-coupling­ reactions compared to the corresponding chlorides or bromides. Unfortunately, the iodides are much more expensive, if commercially available at all, than the other halides. Thus, it is often mandatory to transform the available bromides into the corresponding iodides. The copper-catalyzed aromatic Finkelstein reaction turned out to be the method of choice to prepare a number of highly functionalized iodo(het)aryls, including pyridines, 2,2′-bipyridines, and chiral compounds.

Glycinatocopper(II) complex 1, readily synthesized from copper chloride and glycine was characterized by various techniques including FTIR, XRD, TGA and SEM analysis. The as-synthesized copper complex was found to be a simple and efficient catalyst for the synthesis of aryl and heteroaryl chlorides via aromatic Finkelstein reaction of aryl and heteroaryl bromides in high to excellent yields. The developed glycinatocopper(II) catalyst could easily be recovered from the reaction mixture and reused successfully for several runs without any loss in catalytic efficiency. The developed methodology represents the first example of the use of heterogeneous catalyst for the synthesis of aryl and heteroaryl chlorides via aromatic Finkelstein reaction.

Macromolecular ruthenium complexes are a promising avenue to better and more selective chemotherapeutics. We have previously shown that RAPTA-C [RuCl2(p-cymene)(PTA)], with the water-soluble 1,3,5-phosphaadamantane (PTA) ligand, could be attached to a polymer moiety via nucleophilic substitution of an available iodide with an amide in the PTA ligand. To increase the cell uptake of this macromolecule, we designed an amphiphilic block copolymer capable of self-assembling into polymeric micelles. The block copolymer was prepared by ring-opening polymerization of d,l-lactide (3,6-dimethyl-1,4-dioxane-2,5-dione) using a RAFT agent with an additional hydroxyl functionality, followed by the RAFT copolymerization of 2-hydroxyethyl acrylate (HEA) and 2-chloroethyl methacrylate (CEMA). The Finkelstein reaction and reaction with PTA led to polymers that can readily react with the dimer of RuCl2(p-cymene) to create a macromolecular RAPTA-C drug. RAPTA-C conjugation, micellization, and subsequent cytotoxicity and cell uptake of these polymeric moieties was tested on ovarian cancer A2780, A2780cis, and Ovcar-3 cell lines. Confocal microscopy images confirmed cell uptake of the micelles into the lysosome of the cells, indicative of an endocytic pathway. On average, a 10-fold increase in toxicity was found for the macromolecular drugs when compared to the RAPTA-C molecule. Furthermore, the cell uptake of ruthenium was analyzed and a significant increase was found for the micelles compared to RAPTA-C. Notably, micelles prepared from the polymer containing fewer HEA units had the highest cytotoxicity, the best cell uptake of ruthenium and were highly effective in suppressing the colony-forming ability of cells.

The preparation of 27 isomers of chiral hexahalogeno-4,4'-bipyridines by means of two complementary methods is described. The first one is convergent and based on the LDA-induced 4,4'-dimerization of trihalopyridines, whereas the second method is divergent and achieved through regioselective halogenation reactions of 4,4'-bipyridine-2,2'-diones. Iodine in 2,2'-positions of the 4,4'-bipyridines was introduced by a copper-catalyzed Finkelstein reaction (Buchwald procedure) performed on 2,2'-dibromo derivatives. Selected compounds of this new family of atropisomeric 4,4'-bipyridines were enantioseparated by High Performance Liquid Chromatography (HPLC) on chiral stationary phases and the absolute configurations of the separated enantiomers were assigned by using X-ray diffraction (XRD) analysis. The latter revealed that various halogen bond types are responsible for crystal cohesion.

The facile iodination of aromatic compounds under mild conditions is a great challenge for both organic and medicinal chemistry. Particularly, the synthesis of functionalized aryl iodides by light has long been considered impossible due to their photo-lability, which actually makes aryl iodides popular starting materials in many photo-substitution reactions. Herein, a photo-induced halogen exchange in aryl or vinyl halides has been discovered for the first time. A broad scope of aryl iodides can be prepared in high yields at room temperature under exceptionally mild conditions without any metal or photo-redox catalysts. The presence of a catalytic amount of elemental iodine could promote the reaction significantly.

Cisplatin and some of its derivatives are among the most active cytostatics for cancer treatment. Unfortunately, application of platinum complexes always indicates side effects, and frequently primary or developed resistance of tumour cells appear. Therefore, development of novel analogues especially with natural ligands is expedited. Glyco-functionalized ligands were obtained via ether synthesis with ω-halo ethers, Finkelstein reaction, with further treatment with malonate and final deprotection followed by preparation of the disodium salts. Subsequent complexation led to novel platinum derivatives, the stabilities of which in aqueous solution media were studied.

This is the peer reviewed version of the following article: Fjellaksel, R., Dugalic, D., Demissie, T.B., Riss, P., Hjelstuen, O.-K., Sundset, R. & Hansen, J.H. (2018). An Acylation-Finkelstein Approach to Radioiodination of Bioactives: The Role of Amide Group Anchimeric Assistance. Journal of Physical Organic Chemistry. https://doi.org/10.1002/poc.3835, which has been published in final form at https://doi.org/10.1002/poc.3835. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Herein, we report a straightforward sequential acylation‐Finkelstein approach to achieve iodination of amine containing bioactives. The utility was demonstrated by successful radiolabelling with 123I in high radiochemical yield. Moreover, microwave‐assisted Finkelstein reaction can be employed to enhance conversion and reaction rates to obtain the desired iodides. The method is of interest for radioiodination of amine‐containing bioactives. The mechanistic details of the iodination process were studied by kinetics and density functional theory calculations, which revealed the mechanistic complexity of the reaction involving amide group anchimeric assistance. We disclose a number of fundamental aspects of amide group anchimeric assistance in substitution reactions.

Perfluoromethyldecalin solutions of the fluorous alkyl halides R f 8 (CH 2 ) m X ( m =2, 3; X=Cl, I) are inert toward aqueous NaCl, KI, KCN, and NaOAc. However, substitution occurs at 100 °C in the presence of 10 mol % of the fluorous ammonium salts ( R f 8 (CH 2 ) 2 )(R f 8 (CH 2 ) 5 ) 3 N + I − ( 1 ) or ( R f 8 (CH 2 ) 3 ) 4 N + Br − ( 2 ) (10 mol %), which are fully or partially soluble in perfluoromethyldecalin under these conditions. Stoichiometric reactions of (a) 1 and R f 8 (CH 2 ) 3 Br, and (b) 2 and R f 8 (CH 2 ) 2 I are conducted in perfluoromethyldecalin at 100 °C, and yield the same R f 8 (CH 2 ) m I/ R f 8 (CH 2 ) m Br equilibrium ratio (60–65:40–35). This shows that ionic displacements can take place in extremely nonpolar fluorous phases, and suggests a classical phase transfer mechanism for the catalyzed reactions. Interestingly, the non-fluorous ammonium salt mixture CH 3 (CH 3 (CH 2 ) m ) 3 N + Cl − ( 3 , Aliquat ® 336; m =2:1 7/9) also catalyzes halide substitutions, but under triphasic conditions with 3 suspended between the lower fluorous and upper aqueous layers. NMR experiments establish very low solubilities in both phases, suggesting interfacial catalysis.

Cisplatin, carboplatin, oxaliplatin and further derivatives are worldwide established cytostatics for the treatment of a vast range of tumours. These drugs showed extraordinary success; however, side effects and primary or developed secondary resistance of tumour cells represent severe problems, which prompt the development of novel functionalized platinum complexes. Selectively protected monohydroxy derivatives of glucose and galactose could be etherified by ω-halo ethers. Further, Finkelstein reaction and malonate synthesis gave precursor glycoconjugates which were easily transformed into their (diammine)platinum complexes. First tests with different tumour cell lines show biological activity of the gluco-functionalized platinum complex.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

N (ω-Haloalkyl)amidothiophosphates, N (ω-Haloalkyl)amidothiophosphonates, and N- (ω-Haloalkyl)amidothiophosphinates (Hal = Cl or Br) were obtained in high yields by alkylation of phosphorus(V) acid thioamides with 6h,ω-dihaloalkanes under phase-transfer catalysis (PTC) conditions or through the use of NaH as a base. Thermal rearrangement of N (3-iodopropyl)-or N (4-iodobutyl)amidothiophosphate and N (3-iodopropyl)-or N (4-iodo-butyl)amidothiophosphonate obtained in situ by the Finkelstein reaction provides a convenient route to 2-oxo-1,3,2-thiazaphosphinanes and 2-oxo-1,3,2-thiazaphosphepanes. Reactions of N (ω-Haloalkyl)amidothiophosphinates with NaClO4 in MeCN afforded the first example of stable 1,3,2-thiazaphosphacyclanium salts containing P—C bonds.

A general, rapid, and efficient method for the copper-catalyzed Finkelstein reaction of (hetero)aromatics is developed using continuous flow to generate a variety of aryl iodides.