La dirección de oxyaniones y las interacciones CH-π como elementos clave en una cicloadición [4 + 2] N-heterocíclica
Scott E Allen1, Jessada Mahatthananchai, Jeffrey W Bode
1Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Journal of the American Chemical Society
|July 7, 2012
Resumen
Los catalizadores de carbenos N-heterocíclicos permiten cicloadiciones [4 + 2] altamente selectivas, que producen lactonas valiosas. Los estudios computacionales revelan una vía Diels-Alder concertada impulsada por las interacciones de dirección de oxyaniones y CH-π.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- La catálisis de la catálisis.
- Química computacional es la química computacional.
Sus antecedentes:
- La catálisis de carbenos N-heterocíclicos (NHC) facilita las cicloadiciones [4 + 2], produciendo γ,δ-lactonas δ insaturadas con alta selectividad.
- Los modelos computacionales anteriores de enolados intermedios proporcionaron información poco clara sobre los mecanismos de reacción y los orígenes de la selectividad.
Objetivo del estudio:
- Para dilucidar la vía de reacción y los determinantes de selectividad en las cicloadiciones [4 + 2] catalizadas por NHC.
- Para investigar computacionalmente los resultados estereochemical de estas reacciones.
Principales métodos:
- Se emplearon cálculos de la Teoría Funcional de Densidad (DFT) para modelar la reacción.
- Análisis de estados de transición e intermedios para determinar los mecanismos de reacción.
- Investigación de las interacciones no covalentes que influyen en la estereoselectividad.
Principales resultados:
- La reacción procede a través de un mecanismo Diels-Alder concertado y altamente asincrónico, no por vías escalonadas.
- Se identificaron dos interacciones clave, un efecto de dirección de oxyaniones y una interacción CH-π, como cruciales para una alta enantioselectividad.
- Los cálculos predijeron con precisión la enantioselectividad para varios catalizadores NHC en las reacciones hetero-Diels-Alder.
Conclusiones:
- El estudio aclara el mecanismo de las cicloadiciones [4 + 2] catalizadas por NHC, identificando una vía concertada.
- La dirección de oxyaniones y las interacciones CH-π son clave para lograr un alto control estéreo.
- Los métodos computacionales proporcionan predicciones confiables para el rendimiento del catalizador en estas transformaciones.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Videos de Conceptos Relacionados
01:16Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
01:18Aromatic Hydrocarbon Anions: Structural Overview
Neutral hydrocarbons like cyclopentadiene with an odd number of carbon atoms and one intervening CH2 group in the ring are not aromatic. Cyclopentadiene with 4 π electrons does not satisfy the 4n + 2 π electron rule. Additionally, the intervening CH2 group is sp3 hybridized and lacks a vacant p orbital, thereby interrupting the overlap of p orbitals in a continuous manner and preventing the delocalization of π electrons throughout the ring.
Due to the absence of continuous overlap of p...
Due to the absence of continuous overlap of p...
01:16Cycloaddition Reactions: MO Requirements for Thermal Activation
Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
01:11ortho–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...
02:38Electrophilic Addition to Alkynes: Halogenation
Introduction
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.