Chapter 10 - Asymmetric synthesis of (+)-laurencin using a stereoselective Stevens [1,2]-shift of a sulfonium ylide

Abstract

Abstract This chapter describes a novel approach to medium-sized cyclic ethers using a Stevens [1,2]-shift of a sulfonium ylide derived from a readily accessible 1,3-oxathiane (monothioacetal) precursor with a pendent diazoketoester group. The concise and efficient transformation offered a high degree of chirality transfer and provided sulfur-bridged eight-membered cyclic ethers with retention of configuration at the migrating anomeric center. The resulting sulfur bridge could be conveniently removed by reductive desulfurization to furnish a highly functionalized eight-membered cyclic ether. This transformation has been applied as the key step in an asymmetric formal synthesis of (+)-laurencin by intercepting an advanced intermediate in the total synthesis by Holmes.