Ladder Polyether Synthesis via Epoxide-Opening Cascades Directed by a Disappearing Trimethylsilyl Group

Abstract

Epoxide-opening cascades offer the potential to construct complex polyether natural products expeditiously and in a manner that emulates the biogenesis proposed for these compounds. Herein we provide a full account of our development of a strategy that addresses several important challenges of such cascades. The centerpiece of the method is a trimethylsilyl (SiMe[subscript 3]) group that serves several purposes and leaves no trace of itself by the time the cascade has come to an end. The main function of the SiMe[subscript 3] group is to dictate the regioselectivity of epoxide opening. This strategy is the only general method of effecting endo-selective cascades under basic conditions.