Memory of Chirality in Flow Electrochemistry: Fast Optimisation with DoE and Online 2D‐HPLC. Issue 71 (21st November 2019)

• Record Type: Journal Article
• Authors: Santi, Micol; Seitz, Jakob; Cicala, Rossana; Hardwick, Tomas; Ahmed, Nisar; Wirth, Thomas
• Is Part Of: Chemistry. Volume 25:Issue 71(2019)
• Page Start: 16230
• Page End: 16235
• Publication Date: 2019-11-21
• Subjects: amino acids -- design of experiment -- electrochemistry -- flow chemistry -- memory of chirality -- oxidation; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201904711
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Amino acid derivatives undergo non‐Kolbe electrolysis to afford enantiomerically enriched α‐alkoxyamino derivatives through intermediate chiral carbenium ions. The products contain N, O‐acetals which are important structural motifs found in bioactive natural products. The reaction is performed in a continuous flow electrochemical reactor coupled to a 2D‐HPLC for immediate online analysis. This allowed a fast screening of temperature, electrode material, current, flow‐rate and concentration in a DoE approach. The combination with online HPLC demonstrates that also stereoselective reactions can benefit from a hugely accelerated optimisation by combining flow electrochemistry with multidimensional analysis. Abstract : Asymmetric transformations are quickly optimised using a DoE‐approach with an electrochemical flow reactor attached to a 2D‐HPLC. Cyclic and acyclic N, O‐acetals were obtained in moderate to good yields and enantioselectivities. The highly reactive acyliminium ion serves as a chiral intermediate leading to the desired product with 'memorised" chirality (up to 70 % ee, see scheme) in a short reaction time.