Video Experimental Relacionado

Updated: Dec 21, 2025

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

Published on: May 26, 2019

Síntesis altamente enantioselectiva de Indazoles con un Centro Quaternario Quiral C3 utilizando la Catálisis CuH

Yuxuan Ye¹, Ilia Kevlishvili², Sheng Feng¹

¹Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Journal of the American Chemical Society

|May 16, 2020

Resumen

Ahora es posible lograr la alianza directa C3 de los indazoles, bloques de construcción farmacéuticos cruciales. Esta reacción catalizada por cobre crea valiosos indazoles C3-alilo con alta enantioselectividad, superando las limitaciones sintéticas anteriores.

Área de la Ciencia:

Química orgánica
Química medicinal
Catálisis

Sus antecedentes:

Los 1H-indazoles sustituidos por C3 son andamios farmacéuticos vitales.
La funcionalización directa C3 de los indazoles sigue siendo sintéticamente difícil en comparación con las posiciones N1/N2.

Objetivo del estudio:

Desarrollar un método de alilación selectiva directa C3 para los 1H-indazoles.
Para sintetizar C3-alil 1H-indazoles enriquecidos enantioméricamente con estereocentros cuaternarios.

Principales métodos:

El hidruro de cobre (CuH) catalizó la alilación C3 de los 1H-N-benzoiloxiindazoles.
Cálculos de la teoría funcional de la densidad (DFT) para aclarar el mecanismo de reacción y la selectividad.

Principales resultados:

Síntesis eficiente de diversos C3-alilo 1H-indazoles con estereocentros cuaternarios.
Se obtienen altos niveles de enantioselectividad en la reacción de alilación.
Los cálculos de DFT revelaron un estado de transición tipo Zimmerman-Traxler que rige la enantioselectividad.

Conclusiones:

Se ha establecido una nueva y eficiente alilación selectiva C3 de los indazoles.
La reacción proporciona acceso a valiosos derivados quirales de indazol para aplicaciones farmacéuticas.
La comprensión del estado de transición aclara los determinantes de enantioselectividad para el diseño futuro del catalizador.

Más Videos Relacionados

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

Published on: June 20, 2014

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Published on: June 13, 2022

Videos de Conceptos Relacionados

Prochirality

Prochirality

The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...

Reduction of Alkenes: Asymmetric Catalytic Hydrogenation

Reduction of Alkenes: Asymmetric Catalytic Hydrogenation

Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...

Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration

Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration

The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.

Preparation of 1° Amines: Azide Synthesis

Preparation of 1° Amines: Azide Synthesis

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...

Regioselectivity and Stereochemistry of Hydroboration

Regioselectivity 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.