Effective In Situ Alkoxide Trapping by TMSX in the Presence of TPP Catalyst in Glycidol Acetal Rearrangements

Abstract

This study demonstrates a nucleophile-catalyzed, trimethylsilyl halide-promoted rearrangement reaction of glycidol acetals to form halogenated cyclic acetals. The acetal group has been activated selectively in the presence of trimethylsilyl cation, which is used as in situ-generated alkoxide trapping reagent. Nucleophilic chloride and bromide ions participate in addition reactions with epoxides predominantly via S N 1-type epoxide opening, while non-nucleophilic iodide and triflate ions induce a positive charge at the epoxide carbon. A systematic investigation of acetal-initiated polyene cyclization of epoxy polyenes has been conducted using bicyclic epoxonium ions as transient intermediates. Unfavorable orbital orientation and other stereoelectronic factors hinder the much-anticipated polyene cyclizations. The potential of this method has been showcased through its application in the total synthesis of parvistone A, a chlorinated styryllactone.