Enantioselective aldol reactions with aqueous 2,2-dimethoxyacetaldehyde organocatalyzed by binam-prolinamides under solvent-free conditions

• Published in: Tetrahedron: Asymmetry
• Main Authors: Navarro Moles, Fernando Javier, Bañón Caballero, Abraham, Guillena, Gabriela, Nájera, Carmen
• Other Authors: Universidad de Alicante. Departamento de Química Orgánica, Universidad de Alicante. Instituto Universitario de Síntesis Orgánica, Síntesis Asimétrica (SINTAS)
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 2014
• Subjects: Enantioselective; Aldol; Aqueous; Solvent free; Prolinamides; Química Orgánica; Orca
• Online Access: http://hdl.handle.net/10045/40921; https://doi.org/10.1016/j.tetasy.2014.08.012

Aqueous 2,2-dimethoxyacetaldehyde (60% wt solution) is used as an acceptor in aldol reactions, with cyclic and acyclic ketones and aldehydes as donors, organocatalyzed by 10 mol % of N-tosyl-(Sa)-binam-l-prolinamide [(Sa)-binam-sulfo-l-Pro] at rt under solvent-free conditions. The corresponding monoprotected 2-hydroxy-1,4-dicarbonyl compounds are obtained in good yields and with high levels of diastereo- and enantioselectivity mainly as anti-aldols. In the case of 4-substituted cyclohexanones a desymmetrization process takes place to mainly afford the anti,anti-aldols. 2,2-Dimethyl-1,3-dioxan-5-one allows the synthesis of a useful intermediate for the preparation of carbohydrates in higher yield, de and ee than with l-Pro as the organocatalyst. We thank the financial support from the Spanish Ministerio de Economía y Competitividad (MINECO, Projects CTQ2010-20387 and Consolider Ingenio 2010, CSD2007-00006), FEDER, the Generalitat Valenciana (Prometeo/2009/039), the University of Alicante and the European Commission (ORCA action CM0905). A.B.-C. thanks Spanish MINECO for a predoctoral fellowship (FPU AP2009-3601).