Horeau amplification in the sequential acylative kinetic resolution of (±)-1,2-diols and (±)-1,3-diols in flow

• Published in: Organic & biomolecular chemistry 2021-04, Vol.19 (16), p.362-3627
• Main Authors: Brandolese, Arianna, Greenhalgh, Mark D, Desrues, Titouan, Liu, Xueyang, Qu, Shen, Bressy, Cyril, Smith, Andrew D
• Format: Article
• Language: English
• Subjects: Amplification; Chemical Sciences; Continuous flow; Diols; High-performance liquid chromatography; Liquid chromatography; Microreactors; Optimization; Organic chemistry; Packed beds; Polystyrene; Polystyrene resins; Rate constants; Reaction products; Substrates
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d1ob00304f

The sequential acylative kinetic resolution (KR) of C 2 -symmetric (±)-1,2- syn and (±)-1,3- anti -diols using a packed bed microreactor loaded with the polystyrene-supported isothiourea, HyperBTM, is demonstrated in flow. The sequential KRs of C 2 -symmetric (±)-1,2- syn and (±)-1,3- anti -diols exploits Horeau amplification, with each composed of two successive KR processes, with each substrate class significantly differing in the relative rate constants for each KR process. Optimisation of the continuous flow set-up for both C 2 -symmetric (±)-1,2- syn and (±)-1,3- anti -diol substrate classes allowed isolation of reaction products in both high enantiopurity and yield. In addition to the successful KR of C 2 -symmetric (±)-1,2- syn and (±)-1,3- anti -diols, the application of this process to the more conceptually-complex scenario involving the sequential KR of C 1 -symmetric (±)-1,3- anti -diols was demonstrated, which involves eight independent rate constants. The sequential kinetic resolution of (±)-1,2- syn and (±)-1,3- anti -diols in flow, using the polystyrene supported isothiourea, HyperBTM, gives highly enantioenriched products using the principles of Horeau amplification.