Glyoxylic Acid versus Ethyl Glyoxylate for the Aqueous Enantio­selective Synthesis of α-Hydroxy-γ-Keto Acids and Esters by the N-Tosyl-(S a)-binam-l-prolinamide-Organocatalyzed Aldol Reaction

• Published in: Synthesis
• Main Authors: Navarro Moles, Fernando Javier, Guillena, Gabriela, Nájera, Carmen, Gómez Bengoa, Enrique
• Other Authors: Universidad de Alicante. Departamento de Química Orgánica, Universidad de Alicante. Instituto Universitario de Síntesis Orgánica, Catálisis Estereoselectiva en Síntesis Orgánica (CESO), Síntesis Asimétrica (SINTAS)
• Format: Article in Journal/Newspaper
• Language: English
• Published: Georg Thieme Verlag 2015
• Subjects: Aldol reaction; Organocatalysis; Glyoxylic acid; Prolinamide; Water; Química Orgánica; Orca
• Online Access: http://hdl.handle.net/10045/44611; https://doi.org/10.1055/s-0034-1379546

N-Tosyl-(S a)-binam-l-prolinamide is an efficient catalyst for the aqueous aldol reaction between ketones and glyoxylic acid, as the monohydrate or as an aqueous solution, or a 50% toluene solution of ethyl glyoxylate. These reactions led to the formation of chiral α-hydroxy-γ-keto carboxylic acids and esters in high levels of diastereo- and enantioselectivities (up to 97% ee), providing mainly anti aldol products. Only cyclopentanone and cyclohexane-1,4-dione afforded an almost 1:1 mixture of the syn/anti-diastereoisomers; however, the reaction between 4-phenylcyclohexanone and ethyl glyoxylate gave the corresponding syn,syn-product as the major diastereoisomer. This work was financially supported by the Ministerio de Economia y Competitividad (MINECO: Projects: CTQ2010-20387 and Consolider INGENIO CSD2007-0006), FEDER, the Generalitat Valenciana (Prometeo/2009/039), the University of Alicante, and the EU (ORCA action CM0905).