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

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.

Automated summary

This study demonstrates the sequential acylative kinetic resolution of C-2-symmetric (+/-)-1,2-syn and (+/-)-1,3-anti-diols using a packed bed microreactor loaded with HyperBTM in flow. Each substrate class showed significant differences in relative rate constants for each KR process. Optimization of the flow system allowed for isolation of reaction products in high enantiopurity and yield.