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

Abstract

Syn dihydroxyketone motifs are embedded in awide range of biologically active natural products,h owever the development of stereoselective synthetic methods to assemble these structures has proven ac hallenging task. We report ah ighly diastereoselective method for the synthesis of syn dihydroxyketones from propargylic alcohols,w ith wide scope for application in natural product synthesis.T he reaction sequence involves regioselective cyclisation of propargylic alcohols with incorporation of at riketone to give enol dioxolanes that are then diastereoselectively epoxidised to form unusual spiroepoxide intermediates.H ydrolysis affords syn dihydroxyketones as essentially single diastereisomers.The reaction sequence is operationally simple,o fw ide substrate scope,and remarkably can be efficiently carried out as ao nepot process with no loss of overall yield or diastereoselectivity.Scheme 4. Reaction scope for spiroexpoxide hydrolysis to syn dihydroxyacetones 7a-j.Scheme 5. High diastereoselectivity restored by simple reversal of substituents (6k vs. 6l)i nthe preparation of syn dihydroxyacetone 7k.Scheme 6. One-pot process for direct preparationo fsyn dihydroxyketones from (homochiral)p ropargylic alcohols.