Reacción catalítica enantioselectiva de Strecker de las cetoiminas
Shuji Masumoto1, Hiroyuki Usuda, Masato Suzuki
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Journal of the American Chemical Society
|May 8, 2003
Resumen
Los investigadores desarrollaron una nueva reacción catalítica enantioselectiva de Strecker utilizando un catalizador de gadolinio quiral. Este método sintetiza eficientemente valiosos precursores de ácido alfa-amino de diversas cetoiminas con alta selectividad.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- La catálisis es la catálisis.
- Síntesis asimétrica de síntesis.
Sus antecedentes:
- La reacción de Strecker es un método fundamental para sintetizar los ácidos alfa-amino.
- El desarrollo de variantes enantioselectivas es crucial para acceder a bloques de construcción quirales en productos farmacéuticos y productos químicos finos.
- Las cetoiminas N-difenilfosfinoil representan una clase de sustrato versátil para las transformaciones sintéticas.
Objetivo del estudio:
- Desarrollar una nueva reacción catalítica enantioselectiva de Strecker para las N-difenilfosfinoilcetoiminas.
- Para utilizar un complejo quiral de gadolinio como un catalizador asimétrico para esta transformación.
- Demostrar la amplia aplicabilidad y alta enantioselectividad del método desarrollado.
Principales métodos:
- Preparación de un catalizador complejo de gadolinio quiral a partir de Gd(OiPr) 3 y un ligando derivado de la d-glucosa.
- Cianización enantioselectiva y catalítica de varias cetoiminas N-difenilfosfinoil.
- Análisis del alcance del sustrato y la enantioselectividad utilizando cromatografía quiral.
Principales resultados:
- El complejo quiral de gadolinio catalizó efectivamente la reacción enantioselectiva de Strecker.
- Se lograron altas enantioselectividades para una amplia gama de sustratos, incluidas las cetoiminas aromáticas, etilo, alquilo primario y cetoiminas alfa, beta insaturadas.
- Los productos de cianuración resultantes se convirtieron fácilmente en ácidos alfa-amino disubstituidos y derivados.
Conclusiones:
- Se ha establecido un nuevo método catalítico, eficiente y altamente enantioselectivo para la reacción de Strecker de las N-difenilfosfinoilcetoiminas.
- El método desarrollado ofrece una valiosa ruta a los precursores quirales de ácido alfa-amino.
- El catalizador quiral de gadolinio exhibe una amplia generalidad de sustrato y un alto estereocontrol.
Videos de Conceptos Relacionados
01:21Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
01:10α-Alkylation of Ketones via Enolate Ions
Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the strong interaction...
01:26Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
01:19α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview
The pinacol and McMurry reactions involve the reductive coupling of ketones or aldehydes. Similarly, the bimolecular reductive coupling of two ester molecules in the presence of sodium metal in an aprotic solvent yields an α-hydroxy ketone product. The α-hydroxy ketone is also called acyloin, so the reaction is referred to as ‘acyloin condensation.’
01:27Aldol Condensation with β-Diesters: Knoevenagel Condensation
The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as β-diesters to produce substituted olefins.
01:07Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid.