Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

• Main Authors: Davide Brenna, Elisabetta Massolo, Alessandra Puglisi, Sergio Rossi, Giuseppe Celentano, Maurizio Benaglia, Vito Capriati
• Format: Article
• Language: English
• Published: Beilstein-Institut 2016-12-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: continuous process; DES; organocatalysis; proline; stereoselective aldol reaction
• Online Access: https://doi.org/10.3762/bjoc.12.258

Different deep eutectic solvent (DES) mixtures were studied as reaction media for the continuous synthesis of enantiomerically enriched products by testing different experimental set-ups. L-Proline-catalysed cross-aldol reactions were efficiently performed in continuo, with high yield (99%), anti-stereoselectivity, and enantioselectivity (up to 97% ee). Moreover, using two different DES mixtures, the diastereoselectivity of the process could be tuned, thereby leading to the formation, under different experimental conditions, to both the syn- and the anti-isomer with very high enantioselectivity. The excess of cyclohexanone was recovered and reused, and the reaction could be run and the product isolated without the use of any organic solvent by a proper choice of DES components. The dramatic influence of the reaction media on the reaction rate and stereoselectivity of the process suggests that the intimate architecture of DESs deeply influences the reactivity of different species involved in the catalytic cycle.