Electrophilic Fluorination Reactions Research Articles

Electrophilic Fluorination of Alkenes via Bora‐Wagner–Meerwein Rearrangement. Access to β‐Difluoroalkyl Boronates

AbstractThe electrophilic fluorination of geminal alkyl substituted vinyl‐Bmida derivatives proceeds via bora‐Wagner–Meerwein rearrangement. According to DFT modelling studies this rearrangement occurs with a low activation barrier via a bora‐cyclopropane shaped TS. The Bmida group has a larger migration aptitude than the alkyl moiety in the Wagner–Meerwein rearrangement of the presented electrophilic fluorination reactions.

Electrophilic Fluorination of Alkenes via Bora-Wagner-Meerwein Rearrangement. Access to β-Difluoroalkyl Boronates.

The electrophilic fluorination of geminal alkyl substituted vinyl‐Bmida derivatives proceeds via bora‐Wagner–Meerwein rearrangement. According to DFT modelling studies this rearrangement occurs with a low activation barrier via a bora‐cyclopropane shaped TS. The Bmida group has a larger migration aptitude than the alkyl moiety in the Wagner–Meerwein rearrangement of the presented electrophilic fluorination reactions.

ChemInform Abstract: ortho‐Functionalized Aryltetrazines by Direct Palladium‐Catalyzed C—H Halogenation: Application to Fast Electrophilic Fluorination Reactions.

AbstractReaction conditions are developed for ortho‐selective Pd‐catalyzed C—H functionalization of biphenyl‐1,2,4,5‐tetrazine.

Ortho-Functionalized Aryltetrazines by Direct Palladium-Catalyzed C-H Halogenation: Application to Fast Electrophilic Fluorination Reactions.

A general catalyzed direct C-H functionalization of s-tetrazines is reported. Under mild reaction conditions, N-directed ortho-C-H activation of tetrazines allows the introduction of various functional groups, thus forming carbon-heteroatom bonds: C-X (X=I, Br, Cl) and C-O. Based on this methodology, we developed electrophilic mono- and poly-ortho-fluorination of tetrazines. Microwave irradiation was optimized to afford fluorinated s-aryltetrazines, with satisfactory selectivity, within only ten minutes. This work provides an efficient and practical entry for further accessing highly substituted tetrazine derivatives (iodo, bromo, chloro, fluoro, and acetate precursors). It gives access to ortho-functionalized aryltetrazines which are difficult to obtain by classical Pinner-like syntheses.

Ortho‐Functionalized Aryltetrazines by Direct Palladium‐Catalyzed C−H Halogenation: Application to Fast Electrophilic Fluorination Reactions

AbstractA general catalyzed direct C−H functionalization of s‐tetrazines is reported. Under mild reaction conditions, N‐directed ortho‐C−H activation of tetrazines allows the introduction of various functional groups, thus forming carbon–heteroatom bonds: C−X (X=I, Br, Cl) and C−O. Based on this methodology, we developed electrophilic mono‐ and poly‐ortho‐fluorination of tetrazines. Microwave irradiation was optimized to afford fluorinated s‐aryltetrazines, with satisfactory selectivity, within only ten minutes. This work provides an efficient and practical entry for further accessing highly substituted tetrazine derivatives (iodo, bromo, chloro, fluoro, and acetate precursors). It gives access to ortho‐functionalized aryltetrazines which are difficult to obtain by classical Pinner‐like syntheses.

Asymmetric Synthesis of Fluorine-containing Compounds Using Organocatalysts

Asymmetric synthesis of fluorine-containing compounds using organocatalysts has been extensively investigated and several important strategies have been developed in the last decade. This review focuses on the recent advances in the introduction of the fluorine atom into organic molecules by: i) electrophilic fluorination reactions; ii) the use of easily available fluorine-containing building blocks, both of interest in our research laboratory.

Alternative solvents for electrophilic synthesis of 6‐[18F]fluoro‐L‐DOPA

AbstractOwing to the ozone layer‐depleting properties of chlorofluorocarbon compounds, alternative solvents for electrophilic fluorination reactions are desirable. Chloroform, dichloromethane, acetone or their deuterated analogues were examined as substitutes for Freon‐11 in the electrophilic synthesis of 6‐[18F]fluoro‐L‐DOPA ([18F]FDOPA). CDCl3, CD2Cl2 and C3D6O were found to be suitable solvents in this reaction, with the deuterated solvents providing significantly higher yields than Freon‐11. There were no differences among the solvents in the specific radioactivity, the radiochemical purity, the chemical purity or the microbiological quality of the final product. However, the radiochemical yield of [18F]FDOPA was increased when acetic acid was added to the precursor solution prior to the fluorination reaction. Copyright © 2009 John Wiley & Sons, Ltd.

Selective fluorination of m-tyrosine by OF 2

Fluorine-18 labeled aromatic amino acids are routinely used as tracers in positron emission tomography (PET) to study in vivo metabolic processes. The most versatile method for the production of such radiotracers is electrophilic fluorination of the aromatic amino acid with [ 18F]F 2, which is most commonly produced by the gas-phase nuclear reaction 18O(p, n) 18F. Although [ 18F]F 2 is the major product, considerable amounts of [ 18F]OF 2 (up to 20%) are also produced. Electrophilic fluorination reactions of l-phenylalanine, 3-nitro- l-tyrosine, 4-nitro- dl-phenylalanine, 3,4-dihydroxyphenyl- l-alanine ( l-DOPA), 3- O-methyl- l-DOPA, 3,4-dimethoxy- l-phenylalanine, p-tyrosine and o-tyrosine in H 2O and of m-tyrosine in anhydrous HF (aHF), CF 3SO 3H, CF 3COOH, CH 3COOH, HCOOH and H 2O using OF 2 were investigated. Although F 2 is an efficient fluorinating agent in aHF, electrophilic fluorination reactions using OF 2 were shown to be most efficient in less acidic media such as H 2O. In addition, and contrary to reports that OF 2 and F 2 have similar reactivities, m-tyrosine was the only aromatic system studied that was fluorinated by OF 2 and this was optimum in H 2O for the fluorinated m-tyrosine isomers (total yield, 4.35 ± 0.04%). The presence of [ 18F]OF 2 byproduct has no significant impact on the fluorination of aromatic amino acids investigated in this study and the subsequent production of their corresponding 18F-labeled radiotracers for patient use.

Recent Highlights in Electrophilic Fluorination with 1‐Chloromethyl‐4‐fluoro‐1,4‐diazoniabicyclo[2.2.2]octane Bis(tetrafluoroborate)

AbstractFor Abstract see ChemInform Abstract in Full Text.

Recent highlights in electrophilic fluorination with 1-chloromethyl-4-fluoro- 1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate).

Synthetic and structural aspects of organofluorine compounds continue to be the focal points of vigorous research activities, as evidenced by the appearance of a large number of publications. Among the various useful methodologies for the introduction of fluorine into organic molecules, electrophilic fluorination is a promising and exciting area of research. While a variety of electrophilic fluorinating reagents are available, currently 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) provides a remarkably straightforward and effective route. The breadth of applications realizable from this reagent in its role as a key electrophilic fluorinating reagent is highlighted here. This Account covers the literature for electrophilic fluorination reactions that employ Selectfluor during the period January 1999-January 2003.

ChemInform Abstract: Electrophilic Fluorination Reactions with Fluorine and Some Reagents Directly Derived from it

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Electrophilic fluorination of warfarin, sulfinpyrazone and barbituric acid derivatives

Selective introduction of a fluorine atom into a bioactive molecule often yields compounds with useful and specific properties. We have studied the fluorination of some pharmacologically active compounds by using the N-fluoro[(bistrifluoromethyl)sulfonyl]-imide 1 as the source of “positive fluorine”. 3-[1-Phenyl-3-oxobutyl]-2H-benzopyran-2,4- dione (warfarin) was cleanly fluorinated by treatment with the N-fluoroimide 1 and the corresponding 3-fluorowarfarin 2 (RC 6H 5) was formed. Similarly, sulfinpyrazone and several barbituric acid derivatives afforded corresponding fluorination products 3 (RC 6H 5SO) and 4 (R 1, R 2=H, alk., ar., …). Various other fluorinated analogues of pharmacologically active compounds (e.g. 2, Rp-Cl-C 6H 4; 3, RC 2H 5) have also been synthetized. Desired products have invariably been isolated in high yields. The different reactivities of the various functional groups present in the employed substrate provided interesting information on selectivity and functional group compatibility of electrophilic fluorination reactions with the N-fluoroimide 1. ▪