An Exceptionally Mild Catalytic Thioester Aldol Reaction Inspired by Polyketide Biosynthesis

Abstract
This report details our discovery of a new catalytic ester aldol reaction using malonic acid half thioesters (MAHTs) that directly affords β-hydroxythioesters. The reaction is catalyzed by combination of a Cu(II) salt and an amine base, and it can be performed under exceptionally mild conditions (23 °C, open to the air, wet solvent). Methyl malonic acid half thioesters afforded syn aldol products with distereoselectivities greater than 6:1.