Organocatalytic Asymmetric Alkylation of Aldehydes by S<sub>N</sub>1‐Type Reaction of Alcohols

Cozzi, Pier Giorgio; Benfatti, Fides; Zoli, Luca

doi:10.1002/ange.200805423

Cited by 123 publications

(59 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Die Kombination von Amin VI mit den chiralen Phosporsäuren 34 oder 35 führte mit hoher optischer Reinheit zur g-alkylierten Verbindung 36 als einzigem Reaktionsprodukt. Mechanistisch induziert die Phosphorsäure die Bildung eines chiralen Kontaktionenpaares (das reaktive carbokationische Alkylierungsagens) aus Alkohol 33, [94] das sich synergistisch an einer passenden Kombination mit der chiralen kovalenten Dienamin-Zwischenstufe (entstanden aus der Kondensation des primären Amins VI mit einem Enal) beteiligt. Somit wirkt ein kooperatives katalytisches System, in dem sowohl elektrophile als auch nucleophile chirale Zwischenstufen über ein Netzwerk aus nichtkovalenten Wechselwirkungen miteinander reagieren (Zwischenprodukt w).…”

Section: Dienamin-katalyseunclassified

Katalyse mit primären Cinchona‐Aminen zur asymmetrischen Funktionalisierung von Carbonylverbindungen

Melchiorre

2012

Angewandte Chemie

119

View full text Add to dashboard Cite

Die asymmetrische Aminokatalyse verwendet chirale primäre und sekundäre Amine, um asymmetrische Reaktionen zu katalysieren. Methoden dieser Art haben die Funktionalisierung von Carbonylverbindungen stark vereinfacht und bieten zudem hohe Enantioselektivitäten. Jüngste Fortschritte in der Katalyse mit primären Cinchona‐Aminen haben neue Synthesemöglichkeiten und konzeptionelle Perspektiven aufgezeigt, um die großen Herausforderungen in der Carbonylchemie, die mit bisherigen Ansätzen nicht gelöst werden konnten, anzugehen. Dieser Aufsatz fasst die wichtigsten Meilensteine bei der Entwicklung dieser Katalysatorklasse im historischen Kontext zusammen.

show abstract

Section: Dienamin-katalyseunclassified

Katalyse mit primären Cinchona‐Aminen zur asymmetrischen Funktionalisierung von Carbonylverbindungen

Melchiorre

2012

Angewandte Chemie

119

View full text Add to dashboard Cite

show abstract

“…The stereoselective alkylation of carbonyl groups (aldehydes and ketones) has been achieved through conceptually different activation modes. [7] Recently, we introduced the concept of enantioselective S N 1-type alkylations to organocatalysis, [8,9] and also established the compatibility of indiumA C H T U N G T R E N N U N G (III) Lewis acids with organocatalytic processes mediated by the MacMillan catalyst. [10,11] The compatibility of indiumA C H T U N G T R E N N U N G (III) salts in these processes creates the possibility of using carbocations that cannot be generated in the presence of Brønsted acids.…”

mentioning

confidence: 99%

Indium(III)‐Promoted Organocatalytic Enantioselective α‐Alkylation of Aldehydes with Benzylic and Benzhydrylic Alcohols

et al. 2012

Self Cite

View full text Add to dashboard Cite

Best of both worlds: Organocatalytic SN1‐type reactions promoted by indium(III) salts were performed with activated benzylic and benzhydrylic substrates. High ee values and moderate diastereomeric ratios were obtained. The presence of a 4‐NMe2Ph group, which is useful for further transformations, is essential for obtaining high yields. The synergy of indium(III) salts with organocatalysis is a useful strategy for stereoselective transformations.

show abstract

“…Somewhat surprisingly S N 1-type transformations have been seldom considered in asymmetric organocatalysis until very recently. Pioneered by Petrini, Melchiorre, and co-workers, [7] and considerably extended by Cozzi et al [8] the reaction of stabilized carbocations and p nucleophiles, such as enamines and enol ethers, led the way for a range of selective transformations. Under a variety of S N 1 conditions p nucleophiles such as enamines react fast with soft carbocations, while nucleophiles, including the amine catalyst and water, react slowly with these electrophiles.…”

mentioning

confidence: 99%

Asymmetric α Alkylation of Aldehydes: Efficiency with Elegance

2011

View full text Add to dashboard Cite

alkylation · enamines · nucleophile substitution · organocatalysis · stereoselective catalysis Alkylations using the substitution reaction can be found in the first chapters of introductory level organic chemistry textbooks. Despite its apparent simplicity, the asymmetric a alkylation of aldehydes, even today, presents many unsolved practical problems.[1] Unlike aldol, Mannich, and 1,4-addition reactions, direct a alkylations of aldehydes are often characterized by narrow substrate scope or low stereoselectivity, or often both. As the majority of diastereoselective a alkylations of carbonyl compounds developed use preformed metal or metalloid enolates, [2] the replacement of these enolates by catalytically generated chiral enamines appears straightforward. Regardless of the daunting epimirization problem of the created asymmetric center, the challenge in developing an enantiocatalytic protocol for alkylation is to find reaction conditions for the synthesis of so-called unstabilized enolates in an environment where the nucleophilic catalyst may efficiently compete for the same substrate.The a alkylation of aldehydes using simple alkyl halides as the electrophilic partner is problematic. Reaction conditions have been established for the intramolecular direct S N 2-type a alkylation of haloaldehydes using a-methyl proline as the catalyst.[3] Although this reaction offered a practical solution for the formation of cyclopropanes and five-membered cycles, and is still used in domino transformations, [4] the method performed poorly under intermolecular conditions owing to a number of competing side reactions, and in particular to the deactivation of the nucleophilic catalyst by alkylation. An elegant solution has been presented for the intermolecular asymmetric allylic alkylation (AAA) of a-branched aldehydes; in seminal work by List and Mukherjee the enantiodifferentiation was achieved by a chiral counteranion/anionic ligand rather than a more commonly used neutral ligand. [5] The reaction allows the creation of all-carbon quaternary stereogenic centers, but it is not suitable for the preparation of chiral tertiary centers. Reaction conditions are emerging for intermolecular alkylation by electron-transfer (ET) reactions.[6] The MacMillan group developed an impressive and complex array of highly enantioselective ET-mediated transformations including a allylation, enolation, vinylation, styrenation, polyene cyclization, benzylation, and alkylation of aldehydes.[6c] The inherent limitation of this elegant chemistry is in the substrate scope, as it cannot be used, for example, for the simple a methylation of enolisable aldehydes.In parallel with the ET-mediated a alkylation reactions S N 1-type reactions between stabilized carbocations and enamines are gaining synthetic importance. Somewhat surprisingly S N 1-type transformations have been seldom considered in asymmetric organocatalysis until very recently. Pioneered by Petrini, Melchiorre, and co-workers, [7] and considerably extended by Cozzi et al.[8] the reaction of...

show abstract

Organocatalytic Asymmetric Alkylation of Aldehydes by S_N1‐Type Reaction of Alcohols

Abstract: Fähige Alkohole: Die schwierige enantioselektive katalytische α‐Alkylierung von Aldehyden, eine lange gesuchte Umwandlung, wurde mithilfe von Alkoholen mit der Fähigkeit zur Stabilisierung von Carbokationen erreicht (siehe Schema, TFA=Trifluoressigsäure).

Cited by 123 publications

References 79 publications

Katalyse mit primären Cinchona‐Aminen zur asymmetrischen Funktionalisierung von Carbonylverbindungen

Katalyse mit primären Cinchona‐Aminen zur asymmetrischen Funktionalisierung von Carbonylverbindungen

Indium(III)‐Promoted Organocatalytic Enantioselective α‐Alkylation of Aldehydes with Benzylic and Benzhydrylic Alcohols

Asymmetric α Alkylation of Aldehydes: Efficiency with Elegance

Contact Info

Product

Resources

About

Organocatalytic Asymmetric Alkylation of Aldehydes by SN1‐Type Reaction of Alcohols

Abstract: Fähige Alkohole: Die schwierige enantioselektive katalytische α‐Alkylierung von Aldehyden, eine lange gesuchte Umwandlung, wurde mithilfe von Alkoholen mit der Fähigkeit zur Stabilisierung von Carbokationen erreicht (siehe Schema, TFA=Trifluoressigsäure).

Cited by 123 publications

References 79 publications

Katalyse mit primären Cinchona‐Aminen zur asymmetrischen Funktionalisierung von Carbonylverbindungen

Katalyse mit primären Cinchona‐Aminen zur asymmetrischen Funktionalisierung von Carbonylverbindungen

Indium(III)‐Promoted Organocatalytic Enantioselective α‐Alkylation of Aldehydes with Benzylic and Benzhydrylic Alcohols

Asymmetric α Alkylation of Aldehydes: Efficiency with Elegance

Contact Info

Product

Resources

About

Organocatalytic Asymmetric Alkylation of Aldehydes by S_N1‐Type Reaction of Alcohols