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

Abstract

The sequential acylative kinetic resolution (KR) of C₂-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 C₂-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 C₂-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 C₂-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 C₁-symmetric (±)-1,3-anti-diols was demonstrated, which involves eight independent rate constants.