Proline-catalysed asymmetric amination of α,α-disubstituted aldehydes: synthesis of configurationally stable enantioenriched α-aminoaldehydes

Abstract

Proline-catalysed amination of alpha,alpha-disubstituted racemic aldehydes with azodicarboxylates proceeds smoothly to give configurationally stable scalemic aldehydes and oxazolidinones in up to 86% ee.

Fortschritte bei katalytischen enantioselektiven α‐Aminierungen und α‐Oxygenierungen von Carbonylverbindungen

“…Auch a,a-disubstituierte Aldehyde wurden als geeignete Substrate genannt, obwohl die Selektivitäten bestenfalls mäßig waren. [29] Der Mechanismus dieser Umwandlung zeigt eine sehr interessante Kinetik. [30] Ein neuerer Beitrag von Jørgensen und Mitarbeitern zu diesem Thema beschreibt ein von Chinidin abgeleitetes Alkaloid (b-Isocupreidin, b-ICD) als effizienten Katalysator bei der a-Aminierung von a-Cyanacetaten und b-Dicarbonylverbindungen [Gl.…”

Direct Asymmetric α‐Sulfamidation of α‐Branched Aldehydes: A Novel Approach to Enamine Catalysis

“…[46] With the aid of a procedure developed by List and Jørgensen for the proline-catalysed α-amination of linear aldehydes [47] and ketones [48] with azodicarboxylates, we had been able to show that this strategy can also be transferred to α-branched aldehydes, among them a potential precursor to MCPG, giving ee values of up to 86 %. [49] The scope of this reaction was later extended by Barbas, who used it in the synthesis of two metabotropic glutamate receptor ligands [50] and furthermore introduced a proline-derived tetrazole catalyst in the preparation of the cell adhesion inhibitor BIRT-377. [51] In the meantime, organocatalytic methods have also been devised for the α-amination of α-cyano acetates [52] as well as cyclic β-keto esters and β-keto lactones [53] by catalytic use of cinchona alkaloids, while α-www.eurjoc.orgsubstituted 1,3-diketones have been shown to undergo asymmetric amination under copper catalysis conditions.…”

Enantioselective Organocatalysis in Ionic Liquids: Addition of Aliphatic Aldehydes and Ketones to Diethyl Azodicarboxylate

“…The best results were obtained by using [bmim]PF 6 As an extension of this methodology, Bräse and coworkers [14] described the amination of α,α-disubstituted aldehydes while Barbas and co-workers [15] achieved an l-proline-catalyzed one-pot transformation with the initially formed α-aminated aldehydes being directly trapped in an aldol reaction with acetone. Instead of an azodicarboxylate, nitrosobenzene was identified as a suitable electrophile in related organocatalytic α-oxyaminations of aldehydes.…”