Video Experimental Relacionado
Updated: May 9, 2026
10:44
Isolating Free Carbenes, their Mixed Dimers and Organic Radicals
Published on: April 19, 2019
Funcionalización C-H regioselectiva basada en radicales de los heteroarenos con déficit de electrones: alcance,
Fionn O'Hara1, Donna G Blackmond, Phil S Baran
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|July 18, 2013
Resumen
Los investigadores desarrollaron pautas para controlar la regioquímica en la funcionalización radical de los heterociclos. Esto permite una funcionalización directa predecible y selectiva de compuestos aromáticos complejos, incluidos los productos farmacéuticos.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- Química sintética de la química sintética.
- Química Heterocíclica La Química Heterocíclica es una de las más conocidas.
Sus antecedentes:
- La adición radical ofrece una funcionalización directa de los compuestos heteroaromáticos.
- El pobre control regioquímico ha limitado el uso de procesos radicales.
- Las sales de alquilsulfinato son reactivos emergentes para la funcionalización radical.
Objetivo del estudio:
- Investigar sistemáticamente los factores que influyen en la regioquímica en la funcionalización radical de los heterociclos.
- Desarrollar directrices predictivas para la sustitución regioselectiva en heteroarenos π-deficientes.
- Para demostrar la aplicación de esta metodología en la síntesis de moléculas complejas biológicamente activas.
Principales métodos:
- Investigación sistemática de los efectos de los sustituyentes en la regioselectividad.
- Se utilizan sales de alquilsulfinato para reacciones de adición radical.
- Exploró el impacto del disolvente y el pH en los resultados de la reacción.
Principales resultados:
- Efectos de sustitutos consistentes y aditivos identificados en la regioselectividad.
- Se establecieron pautas predictivas para la sustitución radical regioselectiva en piridinas, pirimidinas, piridazinas y pirazinas.
- Se ha demostrado la introducción exitosa de grupos isopropílicos regioselectivos en diflufenicano y nevirapina.
Conclusiones:
- Es posible lograr un control regioquímico predecible en la funcionalización radical de los heterociclos.
- Los efectos de sustitución proporcionan una base confiable para dirigir la sustitución radical.
- Esta metodología permite la síntesis directa y selectiva de complejos heteroarenos funcionalizados.
Videos de Conceptos Relacionados
01:11Radical Reactivity: Overview
Radicals, the highly reactive species, gain stability by undergoing three different reactions. The first reaction involves a radical-radical coupling, in which a radical combines with another radical, forming a spin‐paired molecule. The second reaction is between a radical and a spin‐paired molecule, generating a new radical and a new spin‐paired molecule. The third reaction is radical decomposition in a unimolecular reaction, forming a new radical and a spin‐paired molecule. These three...
02:17Regioselectivity 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...
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...
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
01:10Radical Reactivity: Steric Effects
The presence of electron-donating, electron-withdrawing, or conjugating groups adjacent to a radical center, imparts electronic stabilization to the radicals. Examples of such electronically-stabilized radicals are triphenylmethyl, tetramethylpiperidine‐N‐oxide, and 2,2‐diphenyl‐1‐picrylhydrazyl. These radicals are remarkably stable and are known as persistent radicals. Some of the persistent radicals can even be isolated and purified.
Along with electronic factors, steric factors also account...
Along with electronic factors, steric factors also account...
01:16Radical Reactivity: Nucleophilic Radicals
Radicals adjacent to electron-donating groups are called nucleophilic radicals. These radicals readily react with electrophilic alkenes. The SOMO–LUMO interactions are the driving force for the reaction, where the high-energy SOMO of the electron-rich, nucleophilic radicals interacts with the low-energy LUMO of the electron-deficient, electrophilic alkenes. Such SOMO–LUMO interactions are the basis of reactive radical traps, affecting the selectivity in radical reactions. For instance, consider...