title: Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents.
abstract: 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 thesyn- and theanti-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.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, I-20133 Milano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Brenna
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, I-20133 Milano, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Massolo
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, I-20133 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Puglisi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, I-20133 Milano, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Celentano
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, I-20133 Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Benaglia
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università di Bari "Aldo Moro", Consorzio C.I.N.M.P.I.S., Via E. Orabona 4, I-70125 Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Capriati
keywords: DES; continuous process; organocatalysis; proline; stereoselective aldol reaction