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A Telescoped Continuous Flow Enantioselective Process for Accessing Intermediates of 1-Aryl-1,3-diols as Chiral
Aitor Maestro1,2, Bence S Nagy2, Sándor B Ötvös2,3
1Department of Organic Chemistry I, University of the Basque Country, UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.
Abstract:
A telescoped continuous flow process is reported for the enantioselective synthesis of chiral precursors of 1-aryl-1,3-diols, intermediates in the synthesis of ezetimibe, dapoxetine, duloxetine, and atomoxetine. The two-step sequence consists of an asymmetric allylboration of readily available aldehydes using a polymer-supported chiral phosphoric acid catalyst to introduce asymmetry, followed by selective epoxidation of the resulting alkene. The process is highly stable for at least 7 h and represents a transition-metal free enantioselective approach to valuable 1-aryl-1,3-diols.
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