Intramolecular Aminofluorination Research Articles

Copper-mediated intramolecular aminofluorination of 1,3-dienes by using nucleophilic fluorine reagents.

A copper-mediated intramolecular aminofluorination of 1,3-dienes is disclosed, in which both AgF and Et3N·3HF can be used as the fluorine source. This protocol provides a variety of pyrrolidines bearing allylic fluorides with excellent regioselectivities and good diastereoselectivities.

Mechanistic insights into silver-catalyzed intramolecular aminofluorination of activated allene

A study has been conducted in the silver-catalyzed intramolecular aminofluorination of activated allene with density functional theory (DFT). It contributes to the proposal that the catalytic cycle mainly contains two stages: (1) cyclization to afford a key binuclear Ag(I)–Ag(I) intermediate IM-Ag containing C–Ag(I) bond and (2) conversion of C–Ag(I) into C–F bond by N-fluorobenzenesulfonmide (NFSI). DFT studies suggest that the key C–F bond-forming reaction occurs via a novel disilver-assisted metathesis process, and this step is the rate-determining step in the whole reaction.

Hypervalent Iodine/HF Reagents for the Synthesis of 3-Fluoropyrrolidines.

The intramolecular aminofluorination of homoallylamine derivatives using a reagent system of PhI(OAc)2 and Py·HF in CH2Cl2 at room temperature for 5 h gave N-tosyl-3-fluoropyrrolidines in good to high yields. Furthermore, the catalytic aminofluorination was furnished by the reaction using p-iodotoluene as a catalyst in the presence of Py·HF as a fluorine source and mCPBA as a terminal oxidant.

Mechanistic study on silver(I)-catalyzed aminofluorination of unactivated alkenes

A study has been performed on the mechanism for the Ag(I)-catalyzed intramolecular aminofluorination of N-arylpent-4-enamides with Selectfluor by means of density functional theory. According to the calculations, the whole catalytic cycle consists of a series of elementary reactions, including formation of the complex (IMC) of the substrate and Ag(H2O)+ (derived from the ligation of H2O to Ag(I)), oxidation of the complex IMC by Selectfluor, deprotonation, homolytic cleavage of the N–Ag(II) bond, intramolecular radical cyclization, and fluorine abstraction. It is suggested that the oxidation of the complex IMC should be the rate-determining step and that the intramolecular radical cyclization determines the regioselectivity of the reaction. Different from that in the decarboxylative fluorination, herein, the deprotonation of the amide is initiated by Ag(II) rather than Ag(I).

ChemInform Abstract: Catalytic Intramolecular Aminofluorination, Oxyfluorination, and Carbofluorination with a Stable and Versatile Hypervalent Fluoroiodine Reagent.

AbstractFor the first time, three types of fluorocyclization reactions are accomplished by using the same fluorination reagent (HFR).

Catalytic Intramolecular Aminofluorination, Oxyfluorination, and Carbofluorination with a Stable and Versatile Hypervalent Fluoroiodine Reagent

AbstractApplication of a fluoroiodine analogue of the Togni reagent was studied in fluorocyclization reactions. In the presence of a transition‐metal catalyst the applied fluoroiodine reagent can be used for aminofluorination, oxyfluorination, and carbofluorination reactions. The described procedure has a very broad synthetic scope for preparation of functionalized hetero‐ and isocyclic compounds having a tertiary fluorine substituent.

Catalytic Intramolecular Aminofluorination, Oxyfluorination, and Carbofluorination with a Stable and Versatile Hypervalent Fluoroiodine Reagent.

Application of a fluoroiodine analogue of the Togni reagent was studied in fluorocyclization reactions. In the presence of a transition-metal catalyst the applied fluoroiodine reagent can be used for aminofluorination, oxyfluorination, and carbofluorination reactions. The described procedure has a very broad synthetic scope for preparation of functionalized hetero- and isocyclic compounds having a tertiary fluorine substituent.

Pd-catalyzed intramolecular aminofluorination of allylic sulfamides

A facile Pd-catalyzed intramolecular aminofluorination reaction of allylic sulfamides was developed that can be used to prepare fluorinated 1,3-diamine derivatives. Acetic acid was essential for regulation to give the major 6-endo cyclization products.

ChemInform Abstract: Boron Trifluoride Etherate Functioning as a Fluorine Source in an Iodosobenzene‐Mediated Intramolecular Aminofluorination of Homoallylic Amines.

A widely used Lewis acid BF3·Et2O was shown to be capable of acting as an efficient fluorinating agent in an intramolecular aminofluorination reaction of homoallylic amines to provide 3-fluoropyrrolidines mediated by a commercially available hypervalent iodine(III) reagent PhIO at room temperature. A mechanism involving a carbocation intermediate was proposed on the basis of several experimental evidence.

ChemInform Abstract: One‐Pot Synthesis of 1‐(Trifluoromethyl)‐4‐fluoro‐1,2‐dihydroisoquinolines and 4,4‐Difluoro‐1,2,3,4‐tetrahydroisoquinolines.

A cascade approach to 1-(trifluoromethyl)-4-fluoro-1,2-dihydroisoquinolines and 4,4-difluorotetrahydroisoquinolines has been developed. The procedure involves a silver-catalyzed intramolecular aminofluorination of alkyne. This one-pot reaction provides an efficient way to synthesize various fluorinated isoquinolines.

Boron Trifluoride Etherate Functioning as a Fluorine Source in an Iodosobenzene-Mediated Intramolecular Aminofluorination of Homoallylic Amines

A widely used Lewis acid BF3·Et2O was shown to be capable of acting as an efficient fluorinating agent in an intramolecular aminofluorination reaction of homoallylic amines to provide 3-fluoropyrrolidines mediated by a commercially available hypervalent iodine(III) reagent PhIO at room temperature. A mechanism involving a carbocation intermediate was proposed on the basis of several experimental evidence.

Iodoarene-catalyzed fluorination and aminofluorination by an Ar-I/HF·pyridine/mCPBA system

We have developed the iodoarene-catalyzed fluorination of carbonyl compounds and intramolecular aminofluorination of ω-amino-alkenes using HF/mCPBA.

One-Pot Synthesis of 1-(Trifluoromethyl)-4-fluoro-1,2-dihydroisoquinolines and 4,4-Difluoro-1,2,3,4-tetrahydroisoquinolines

A cascade approach to 1-(trifluoromethyl)-4-fluoro-1,2-dihydroisoquinolines and 4,4-difluorotetrahydroisoquinolines has been developed. The procedure involves a silver-catalyzed intramolecular aminofluorination of alkyne. This one-pot reaction provides an efficient way to synthesize various fluorinated isoquinolines.

ChemInform Abstract: Silver‐Catalyzed Radical Aminofluorination of Unactivated Alkenes in Aqueous Media.

We report herein a mild and catalytic intramolecular aminofluorination of unactivated alkenes. Thus, with the catalysis of AgNO3, the reactions of various N-arylpent-4-enamides with Selectfluor reagent in CH2Cl2/H2O led to the efficient synthesis of 5-fluoromethyl-substituted γ-lactams. A mechanism involving silver-catalyzed oxidative generation of amidyl radicals and silver-assisted fluorine atom transfer was proposed.

An Efficient Synthesis of Fluorinated Azaheterocycles by Aminocyclization of Alkenes

A general and efficient approach to important fluorinated azaheterocycles has been developed by incorporating nucleophilic fluorination into alkene difunctionalization. This intramolecular aminofluorination transformation of alkenes has been achieved via the aminocyclization of reactive unsaturated N-iodoamines, which can be generated in situ from either unsaturated N-chloramines or their amine precursors in a one-pot protocol.

Silver-Catalyzed Radical Aminofluorination of Unactivated Alkenes in Aqueous Media

We report herein a mild and catalytic intramolecular aminofluorination of unactivated alkenes. Thus, with the catalysis of AgNO3, the reactions of various N-arylpent-4-enamides with Selectfluor reagent in CH2Cl2/H2O led to the efficient synthesis of 5-fluoromethyl-substituted γ-lactams. A mechanism involving silver-catalyzed oxidative generation of amidyl radicals and silver-assisted fluorine atom transfer was proposed.

ChemInform Abstract: Ag(I)‐Catalyzed Aminofluorination of Alkynes: Efficient Synthesis of 4‐Fluoroisoquinolines and 4‐Fluoropyrrolo[α]isoquinolines.

AbstractRelated compounds such as (IV), (VI), and (XII) are also available.

Regioselective palladium-catalyzed intramolecular oxidative aminofluorination of unactivated alkenes

A novel Pd-catalyzed regioselective intramolecular aminofluorination of unactivated alkenes has been developed, which is an efficient method for the synthesis of a variety of monofluoromethylated nitrogen-containing heterocycles.

ChemInform Abstract: Silver‐Catalyzed Fluorination Reactions

AbstractReview: 29 refs.

Silver-Catalyzed Fluorination Reactions

The silver-catalyzed fluorination has been developed for introducing a fluorine atom into organic compounds. Recent progress in this area is reviewed with an emphasis on the silver-catalyzed intramolecular aminofluorination of allenes.