Highly Diastereoselective Synthesis of Syn-1,3-Dihydroxyketone Motifs from Propargylic Alcohols via Spiroepoxide Intermediates

Angew Chem Int Ed Engl. 2019 Aug 19;58(34):11830-11835. doi: 10.1002/anie.201905736. Epub 2019 Jul 10.


Syn dihydroxyketone motifs are embedded in a wide range of biologically active natural products, however the development of stereoselective synthetic methods to assemble these structures has proven a challenging task. We report a highly diastereoselective method for the synthesis of syn dihydroxyketones from propargylic alcohols, with wide scope for application in natural product synthesis. The reaction sequence involves regioselective cyclisation of propargylic alcohols with incorporation of a triketone to give enol dioxolanes that are then diastereoselectively epoxidised to form unusual spiroepoxide intermediates. Hydrolysis affords syn dihydroxyketones as essentially single diastereisomers. The reaction sequence is operationally simple, of wide substrate scope, and remarkably can be efficiently carried out as a one-pot process with no loss of overall yield or diastereoselectivity.

Keywords: dihydroxyketones; epoxidation; natural products; spiroepoxides; stereoselective synthesis.

Publication types

  • Research Support, Non-U.S. Gov't