Syn‐Selective Epoxidation of Chiral Terminal Allylic Alcohols with a Titanium Salalen Catalyst and Hydrogen Peroxide

Abstract

In the Sharpless asymmetric epoxidation of chiral secondary allylic alcohols, one substrate enantiomer is predominantly converted to the anti‐epoxy alcohol. We herein report the first highly syn‐selective epoxidation of terminal allylic alcohols using a titanium salalen complex as catalyst, at room temperature, and aqueous hydrogen peroxide as oxidant. With enantiopure terminal allylic alcohols as substrates, the epoxy alcohols were obtained with up to 98 % yield and up to >99 : 1 dr (syn). Catalyst loadings as low as 1 mol % can be applied without eroding the syn‐diastereoselectivity. Modification of the allylic alcohol to an ether does not affect the diastereoselectivity either [>99 : 1 dr (syn)]. Inverting the catalyst configuration leads to the anti‐product, albeit at lower dr (ca. 20 : 1). The synthetic potential is demonstrated by a short, gram‐scale preparation of a tetrahydrofuran building block with three stereocenters, involving two titanium salalen catalyzed epoxidation steps.