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

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).