The use of stereoselective phase-transfer catalysis as a reliable method for the enantioselec- tive synthesis of optically active α-amino acid derivatives using achiral Schiff base esters has been well-developed in batch in the last 40 years. Recently, continuous flow technology has become of great interest in the academy and industry, since it offers safer process operating conditions and higher efficiency compared to a traditional batch processing. Herein, we wish to report the first example of enantioselective phase transfer benzylation of alanine Schiff base ester, under continuous flow conditions. Two different methodologies were investigated: a liquid-solid phase transfer catalytic benzylation using a packed-bed reactor and a liquid-liquid phase transfer catalytic benzylation in continuous stirred-tank reactors. Liquid-liquid phase transfer process in flow showed slightly better productivity than the batch process, while solid-liquid phase transfer benzylation proved much more advantageous in terms of productivity and space-time yield. Furthermore, continuous flow system allowed the isolation of benzylated product without any work up, with a significant simplification of the process. In both cases, phase transfer asymmetric benzylation promoted by Maruoka catalyst demonstrated high enantioselectivity of target quaternary amino ester in flow, up to 93% ee.

Laboratory Scale Continuous Flow Systems for the Enantioselective Phase Transfer Catalytic Synthesis of Quaternary Amino Acids / M. Krstic, S. Rossi, M. Sanz, A. Puglisi. - In: MOLECULES. - ISSN 1420-3049. - 28:(2023 Jan 19), pp. 1002.1-1002.12. [10.3390/molecules28031002]

Laboratory Scale Continuous Flow Systems for the Enantioselective Phase Transfer Catalytic Synthesis of Quaternary Amino Acids

M. Krstic
Primo
;
S. Rossi
Secondo
;
A. Puglisi
Ultimo
2023

Abstract

The use of stereoselective phase-transfer catalysis as a reliable method for the enantioselec- tive synthesis of optically active α-amino acid derivatives using achiral Schiff base esters has been well-developed in batch in the last 40 years. Recently, continuous flow technology has become of great interest in the academy and industry, since it offers safer process operating conditions and higher efficiency compared to a traditional batch processing. Herein, we wish to report the first example of enantioselective phase transfer benzylation of alanine Schiff base ester, under continuous flow conditions. Two different methodologies were investigated: a liquid-solid phase transfer catalytic benzylation using a packed-bed reactor and a liquid-liquid phase transfer catalytic benzylation in continuous stirred-tank reactors. Liquid-liquid phase transfer process in flow showed slightly better productivity than the batch process, while solid-liquid phase transfer benzylation proved much more advantageous in terms of productivity and space-time yield. Furthermore, continuous flow system allowed the isolation of benzylated product without any work up, with a significant simplification of the process. In both cases, phase transfer asymmetric benzylation promoted by Maruoka catalyst demonstrated high enantioselectivity of target quaternary amino ester in flow, up to 93% ee.
continuous flow; quaternary stereocenter; phase transfer catalysis (PTC); enantioselective synthesis; packed-bed reactor; continuous stirred tank reactor; asymmetric catalysis
Settore CHIM/06 - Chimica Organica
H20MCITNIF18MBENA_01 - Enabling TECHNOlogies-driven chemistry: a tailored TRAINing research program for batch and flow synthesis of chiral amino derivatives (TECHNOTRAIN) - BENAGLIA, MAURIZIO - H20MCITNIF - Horizon 2020_Marie Skłodowska-Curie actions-Innovative Training Network (ITN)/Individual Fellowships (IF) - 2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/951457
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