Silver-mediated fluorination of potassium aryltrifluoroborates with Selectfluor®

A simple and practical procedure for the silver-mediated fluorination of aryl- and heteroaryltrifluoroborates with electrophilic fluorine from Selectfluor^® and LiOH·H₂O is presented. The reaction procedure is simple and easy to set up, the process produces fluorinated arenes and heteroarenes in good to excellent yields and a wide range of electronically and structurally diverse substrates are tolerated.     

Regio- and diastereoselective fluorination of alicyclic β-amino acids

A regio- and stereoselective approach to fluorinated β-aminocyclohexene or cyclohexane esters has been developed, starting from a bicyclic β-lactam (1). The procedure involves six or seven steps, based on regio- and stereoselective iodolactonization, lactone opening and hydroxy-fluorine exchange. The method has been extended to the synthesis of fluorinated amino ester enantiomers.     

An efficient catalytic enantioselective fluorination of β-ketophosphonates using chiral palladium complexes

On the basis of our Pd enolate chemistry, we have succeeded in developing an efficient catalytic enantioselective fluorination of β-ketophosphonates. In the presence of chiral Pd complexes 1 (1-10 mol %), various substrates including cyclic and acyclic β-ketophosphonates underwent the reaction with N-fluorobenzenesulfonimide (NFSI) in EtOH to give the corresponding fluorinated products in a highly enantioselective manner (94-98% ee).     

Hypervalent phenyl-λ3-iodane-mediated para-selective aromatic fluorination of 3-phenylpropyl ethers

Exposure of 3-phenylpropyl ethers to an activated iodosylbenzene monomer·18-crown-6 complex [PhI(OH)BF(4)·18C6] in the presence of BF(3)-Et(2)O and water results in the para-selective monofluorination of benzene ring via neighboring alkoxy group participation and directly affords 3-(4-fluorophenyl)propyl ethers regioselectively in good yields.     

Regioselective fluorination in synthesis of deoxyfluoro quercitols from d-(−)-quinic acid

A facile synthesis of six new deoxyfluoro querciotls from d-(−)-quinic acid is described. The key steps involve the regioselective fluorination as well as highly stereoselective dihydroxylation. These synthetic deoxyfluoro quercitols are considered as potential glycosidase inhibitors.     

Recent advances in radical-mediated fluorination through C–H and C–C bond cleavage

The C–H and C–C bonds are abundant in organic compounds, yet generally inert in chemical transformations. Therefore, direct functionalization of inert chemical bonds remains challenging. The fluorine-containing compounds are of special interest for their uses in medicinal chemistry. Direct fluorination of C–H and C–C bonds undoubtedly represents one of the most ideal and attractive approaches to incorporate fluorine atom into complex molecules. Herein, we summarize the recent advances in radical-mediated C–H and C–C bond fluorination. Three types of transformations are discussed: (1) direct C–H abstraction/fluorination of alkanes; (2) decarboxylative fluorination of alkyl carboxylic acids; (3) ring-opening fluorination.     

Selective synthesis of α-fluoro-β-keto- and α-fluoro-β-aminophosphonates via electrophilic fluorination by selectfluor

A series of α-mono- and α,α-difluoro-β-ketophosphonates were synthesized in moderate to good yields with excellent selectivities via electrophilic fluorination by Selectfluor. Subsequently, synthetic potential of the obtained α-monofluoro-β-ketophosphonates was demonstrated by their application in synthesis of α-monofluoro-β-aminophosphonates, useful building blocks in the preparation of phosphapeptides.     

Control of intramolecular π-π stacking interaction in cationic iridium complexes via fluorination of pendant phenyl rings

Intramolecular π-π stacking interaction in one kind of phosphorescent cationic iridium complexes has been controlled through fluorination of the pendant phenyl rings on the ancillary ligands. Two blue-green-emitting cationic iridium complexes, [Ir(ppy)(2)(F2phpzpy)]PF(6) (2) and [Ir(ppy)(2)(F5phpzpy)]PF(6) (3), with the pendant phenyl rings on the ancillary ligands substituted with two and five fluorine atoms, respectively, have been synthesized and compared to the parent complex, [Ir(ppy)(2)(phpzpy)]PF(6) (1). Here Hppy is 2-phenylpyridine, F2phpzpy is 2-(1-(3,5-difluorophenyl)-1H-pyrazol-3-yl)pyridine, F5phpzpy is 2-(1-pentafluorophenyl-1H-pyrazol-3-yl)-pyridine, and phpzpy is 2-(1-phenyl-1H-pyrazol-3-yl)pyridine. Single crystal structures reveal that the pendant phenyl rings on the ancillary ligands stack to the phenyl rings of the ppy ligands, with dihedral angles of 21°, 18°, and 5.0° between least-squares planes for complexes 1, 2, and 3, respectively, and centroid-centroid distances of 3.75, 3.65, and 3.52 ? for complexes 1, 2, and 3, respectively, indicating progressively reinforced intramolecular π-π stacking interactions from complexes 1 to 2 and 3. Compared to complex 1, complex 3 with a significantly reinforced intramolecular face-to-face π-π stacking interaction exhibits a significantly enhanced (by 1 order of magnitude) photoluminescent efficiency in solution. Theoretical calculations reveal that in complex 3 it is unfavorable in energy for the pentafluorophenyl ring to swing by a large degree and the intramolecular π-π stacking interaction remains on the lowest triplet state.     

Construction of fluorinated pyrazole derivatives via a one-pot tandem C–H insertion/electrophilic fluorination reaction

A series of 4-fluoro-pyrazole derivatives were synthesized in moderate to good yields via a one-pot tandem procedure involving an Rh₂(OAc)₄-catalyzed C–H insertion and an electrophilic fluorination with N-fluorobenzenesulfonimide (NFSI).     

Ansa versus spiro substitution of cyclophosphazenes: is fluorination essential for ansa to spiro transformation of cyclophosphazenes?

Fluorinated ansa substituted cyclophosphazenes endo-FcCH(2)P(S)(CH(2)O)(2)[P(F)N](2)(F(2)PN) [Fc = ferrocenyl] (1) and exo-FcCH(2)P(S)(CH(2)O)(2)[P(F)N](2)(F(2)PN) (2) readily transform to the spirocyclic compound [FcCH(2)P(S)(CH(2)O)(2)PN](F(2)PN)(2) (3) not only in the presence of CsF but also with non-fluorinated bases such as Cs(2)CO(3), K(2)CO(3), KOBu(t), Et(3)N, DABCO, DBN, and DBU. The analogous tetrachloro ansa compound exo-FcCH(2)P(S)(CH(2)O)(2)[P(Cl)N](2)(Cl(2)PN) (5), however, did not transform to the chlorinated spiro compound (6) in the presence of these bases. With excess of CsF, P-Cl bonds of 5 were found to undergo fluorination leading to the formation of 2, which transformed to spirocyclic compound 3. Time dependent (31)P NMR spectroscopy was used to monitor this transformation. Crystal structure studies on the ansa substituted compounds 4 and 5 have shown weak bonding interactions involving C-H...Cl, C-H...O, and C-H...S interactions.     

Unstrained C–C bond activation and directed fluorination through photocatalytically-generated radical cations

Expanding the repertoire of controlled radical fluorination techniques, we present a photosensitized unstrained C–C bond activation/directed monofluorination method using Selectfluor and 9-fluorenone. The reaction is amenable to the opening of multiple 1-acetal-2-aryl substituted rings to yield ω-fluoro carboxylic acids, esters, alcohols, and ketones with relative ease. Initial mechanistic insight suggests radical ion intermediates.     

One-pot synthesis of α,α-difluoroimines from alkynes through tandem catalytic diboration/fluorination/imination reaction

Tandem catalytic diboration/fluorination/imination of arylacetylenes leads to the formation of α,α-difluoroimines, where the adjacent CN and C-F₂ bonds are formed simultaneously. The convenient one-pot protocol involves a Pt(0)-catalyzed diboration of terminal or internal arylalkynes followed by electrophilic fluorination with Selectfluor in the presence of primary amines and a dehydrating agent. A plausible mechanism for the three consecutive steps (diboration/fluorination/imination) is suggested in accordance with the electronic properties of the substrates. Alkynes/catalytic diboration/alkenyl diboronate esters/Selectfluor/electrophilic fluorination/α,α-difluoroimines.     

The investigation of fluorination reaction of p-substituted benzenesulfonimides with fluorine–nitrogen mixed gas to synthesize NFSI analogues

This paper studied the fluorination reaction of p-substituted benzenesulfonimides with diluted elemental fluorine to synthesize N-fluoro-benzenesulfonimide (NFSI) analogues. Several synthetic methods were compared and we found that, for many p-substituted benzenesulfonimides, the fluorination of their sodium salts with 10% F₂–N₂ mixed gas in acetonitrile at room temperature could afford NFSI analogues in moderate to good yields.     

Anodic fluorination of 4-methoxy-1-naphthol and 4-nitroanisole using Et3N · 5 HF in mixed nonaqueous solvent

Anodic fluorination of 4-methoxy-1-naphthol and 4-nitroanisole has been investigated in a mixed nonaqueous solvent using Et₃N · 5 HF as supporting electrolyte as well as fluorine source. In order to avoid the formation of polymer on the anode, pulse electrolysis was carried out without exchanging the electrodes. The proposed procedure ensures excellent yield at room temperature, shortest reaction time, and easy work-up which provide additional advantages in the context of green chemistry. Experimental parameters of the reaction are discussed.     

An efficient fluorination of β-ketosulfones promoted by a room-temperature ionic liquid at ambient conditions under ultrasound irradiation using Selectfluor~(TM) F-TEDA-BF_4

<正>The fluorination reaction involving aβ-ketosulfones by Selectfluor~(TM) was efficiently promoted by the ionic liquid,[Hbim]BF_4 (EL) as a reaction medium with methanol as co-solvent at room temperature under ultrasonic irradiation to afford the corresponding mono and difluoro-β-ketosulfones in excellent yields.The advantages of this method include among others the use of a recyclable, non-volatile ionic liquid,which promotes this protocol under room temperature without the requirement of any added catalyst under ultrasonic irradiation.     

A guide to use fluorinated aromatic bulky cations for stable and high-performance 2D/3D perovskite solar cells: The more fluorination the better?

While serious stability issues impede the commercialization of perovskite solar cells(PSCs),twodimensional(2 D) perovskites based on fluorinated bulky cations have emerged as more intrinsically stable materials.However,the influence of fluorination degree of the bulky aromatic cation on the performance of resulting PSCs has not been scrutinized.Here,2 D perovskites(FxPEA)2 PbI₄(x=1,2,3,5) are grown in situ on the surface of the three-dimensional(3 D) perovskite and demonstrate effecti...     

Evaluation of the radiochemical impurities arising during the competitive fluorination of nosyl group during the synthesis of 3′-deoxy-3′-fluorothymidine, [18F]FLT

The study is aimed at the analysis and identification of radiochemical and chemical impurities present in [¹⁸F]FLT synthesized by a simplified combination-column purification procedure, instead of the currently used HPLC purification. HPLC analysis of the final product showed an anionic radioactive byproduct, which was established as [¹⁸F]4-FBSA. The identity of the product was also confirmed by the radiofluorination of nosyl chloride. Mass spectrum analysis of both a decayed sample of [¹⁸F]FLT and fluorinated nosyl chloride showed a major peak at 242. We have also investigated the possible interference of this byproduct during PET-imaging in rabbits.