Directing group-free endo-selective epoxide-opening cascades

Abstract

[image] The proposed biogenesis of the ladder polyethers features a dramatic series of epoxide opening reactions, elegantly accounts for the structural and stereochemical features of all related natural products, and, in principle, could significantly simplify the synthesis of these extraordinarily complex molecules. In practice, however, such cascades are strongly disfavored, and non-natural directing groups must be covalently attached to each epoxide to overcome this inherent bias. We report herein a general method for directing group-free cascades that also supports the postulated biosynthesis. The two salient aspects of this strategy are a single design principle (a template) and a promoter that both donates and accepts hydrogen bonds. Water is the superior promoter, and it is most effective at approximately pH 7.