Video Experimental Relacionado

Updated: Sep 9, 2025

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

Published on: July 28, 2018

Enantioselectivo Pd-Catalizado Nucleófilo C ((sp³) -H (Radio) fluoración

Nikita Chekshin¹, Luo-Yan Liu¹, D Quang Phan¹

¹Department of Chemistry, The Scripps Research Institute; 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Nature catalysis

|September 2, 2025

Resumen

Los investigadores desarrollaron un nuevo método catalizado por el paladio para la fluoración C-H enantioselectiva de amidas y lactamas. Este avance permite la síntesis de valiosos compuestos fluorados quirales y facilita el radiomarcado 18F para el descubrimiento de fármacos.

Área de la Ciencia:

Química orgánica
Catálisis
Química medicinal

Sus antecedentes:

Las moléculas orgánicas fluoradas quirales tienen una gran demanda de productos farmacéuticos.
La fluoración enantioselectiva de C-H, especialmente utilizando fuentes de flúor nucleófilas, es un desafío sintético significativo.
Los métodos existentes carecen de fluoración nucleofílica enantioselectiva de enlaces inertes C ((sp3) -H.

Objetivo del estudio:

Desarrollar un sistema catalítico para la fluoración C-H nucleofílica altamente regionalizada y enantioselectiva.
Para permitir la síntesis de amidas y lactamos fluorados quirales.
Aplicar el método para el etiquetado radioactivo con 18F en etapas avanzadas.

Principales métodos:

Diseño y desarrollo de un sistema catalítico basado en paladio con ligandos MPASA bifuncionales.
Aplicación del catalizador para la fluoración nucleofílica beta-C ((sp3) -H de las amidas y los lactamos.
Estudios mecánicos para elucidar la vía de formación de enlaces C-F.

Principales resultados:

Se obtiene una fluoración altamente regio- y enantioselectiva nucleofílica beta-C ((sp3) -H de amidas y lactamas.
Se ha demostrado la rápida conversión de productos fluorados en aminas quirales y cetonas.
Se ha aplicado con éxito el método de etiquetado radioactivo de derivados farmacéuticos con [18F]KF en fase avanzada.

Conclusiones:

El sistema de catalizador Pd desarrollado con ligandos MPASA es eficaz para la fluoración nucleofílica C-H enantioselectiva.
Este método proporciona acceso a valiosos bloques de construcción quirales fluorados para la química medicinal.
El enfoque es adecuado para el radiomarcado con 18F, lo que ayuda en el desarrollo de fármacos y la obtención de imágenes.

Más Videos Relacionados

Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry

Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry

Published on: August 19, 2012

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

Published on: September 12, 2018

Videos de Conceptos Relacionados

Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene

Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene

Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are difficult to achieve. Fluorine is so reactive that its reaction with benzene is difficult to control, resulting in poor yields of monofluoroaromatic products. To address this, Selectfluor reagent is used as a fluorine source in which a fluorine atom is bonded to a positively charged nitrogen.

Nucleophilic Aromatic Substitution: Elimination–Addition

Nucleophilic Aromatic Substitution: Elimination–Addition

Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is...

ortho–para-Directing Activators: –CH3, –OH, –&NoBreak;NH2, –OCH3

ortho–para-Directing Activators: –CH₃, –OH, –⁠NH₂, –OCH₃

All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic S_N1

Treating arylamines with nitrous acid gives aryldiazonium salts that are effective substrates in nucleophilic aromatic substitution reactions. The diazonio group in these salts can be easily displaced by different nucleophiles, yielding a wide variety of substituted benzenes. The leaving group departs as nitrogen gas, and this easy elimination is the driving force for the substitution reaction.
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...

Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule

Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule

If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...

Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)

Nucleophilic Aromatic Substitution: Addition–Elimination (S_NAr)

Nucleophilic substitution in aromatic compounds is feasible in substrates bearing strong electron-withdrawing substituents positioned ortho or para to the leaving group. The reaction proceeds via two steps: the addition of the nucleophile and the elimination of the leaving group.
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...