Estereoselectividad de la reacción de anulación de benceno: transferencia eficiente de quiralidad central a axial
Andrei V Vorogushin1, William D Wulff, Hans-Jürgen Hansen
1Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
Journal of the American Chemical Society
|June 6, 2002
Resumen
Los investigadores lograron una alta diastereoselectividad en la síntesis de allocolchicinoides utilizando complejos de carbenos de Fischer y 1-pentyne. Otras reacciones mostraron una selectividad moderada, que mejoró en condiciones termodinámicas, ofreciendo una vía a atropisómeros específicos.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- Química organometálica Química orgánica de los metales.
- Química sintética de la química sintética.
Sus antecedentes:
- Los complejos de carbenos de Fischer son reactivos versátiles en la síntesis orgánica.
- El control de la estereoquímica, particularmente la diastereoselectividad y el atropisomerismo, es crucial en la síntesis de moléculas complejas como los allocolchicinoides.
Objetivo del estudio:
- Investigar la diastereoselectividad de las reacciones que involucran complejos de carbenos de Fischer y 1-pentina para la síntesis de allocolchicinoides.
- Explorar métodos para mejorar la diastereoselectividad, especialmente para obtener atropisómeros específicos.
Principales métodos:
- Reacción de los complejos de carbenos de Fischer (4) con 1-pentina para formar alocolchicinoides (5).
- Reacción análoga de diferentes complejos de carbenos de Fischer (8) para formar el producto (9).
- Aplicación de condiciones termodinámicas para influir en la diastereoselectividad.
Principales resultados:
- Se logró una alta diastereoselectividad en la preparación de allocolchicinoides configuralmente estables (5).
- La reacción de los complejos (8) produjo un producto (9) con moderada diastereoselectividad para el atropisómero opuesto.
- Las condiciones termodinámicas mejoraron significativamente la diastereoselectividad para el atropisómero deseado.
Conclusiones:
- Los complejos de carbenos de Fischer proporcionan una ruta efectiva a los allocolquicinoides con alta diastereoselectividad.
- El resultado estereoquímico puede ser modulado, con un control termodinámico que ofrece una estrategia para acceder a atropisómeros específicos.
Más Videos Relacionados
09:08Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite Extraction Protocol
Published on: April 2, 2018
05:34Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of α,β-Unsaturated Compounds and Alkynes
Published on: December 16, 2019
Videos de Conceptos Relacionados
02:43E1 Reaction: Stereochemistry and Regiochemistry
One of the critical aspects of the E1 reaction mechanism, as also observed in E2, is the regiochemistry, with multiple regioisomers obtained as products. In the example discussed, the presence of water as a weak base favors elimination over substitution to generate two alkenes. Given that alkenes’ stability increases with the number of alkyl groups across the double bond, typically, E1 reactions lead to the Zaitsev product, for this is more substituted and stable than the Hofmann product.
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...
02:35Regioselectivity of Electrophilic Additions-Peroxide Effect
In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov’s rule. For example, the addition of hydrogen bromide to 2-methylpropene in the presence of peroxides gives 1-bromo-2-methylpropane. This addition reaction proceeds via a free radical mechanism, which reverses the regioselectivity. The free radical reaction mechanism involves three stages: initiation, propagation, and termination.
03:08Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
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.
01:18Benzene to 1,4-Cyclohexadiene: Birch Reduction Mechanism
Birch reduction uses solvated electrons as reducing agents. The reaction converts benzene to 1,4-cyclohexadiene. The reaction proceeds by the transfer of a single electron to the ring to form a benzene radical anion. This anion is highly basic—it abstracts a proton from the alcohol to form a cyclohexadienyl radical. Another single electron transfer gives the cyclohexadienyl anion. A proton transfer from the alcohol forms 1,4-cyclohexadiene. Since this reduction occurs via radical anion...