Chemistry of the herbicidins. Reactivity of silyl enol ethers derived from simple and carbohydrate-based tetrahydropyrans

Abstract

Details are described of preliminary synthetic studies, based on Lewis acid-mediated alkylation of a silyl enol ether, that were directed towards the C₁₁ glycoside of the herbicidin class of nucleosides. The chemistry presented focuses on limitations encountered with the reactivity of both the electrophilic and nucleophilic components designed to serve this longer term synthetic objective. α-Chloro sulfide 6 readily undergoes a Lewis acid-promoted internal redox reaction leading to sulfide 8; this is a consequence of the O-benzyl protecting group used at C-3 of chloro sulfide 6. This pathway is avoided by use of O-silyl protection, and reaction of the silyl-protected α-chloro sulfide 11 with the simple heterocyclic silyl enol ether 5 gives the herbicidin models 13a and 13b incorporating the required furano-pyrano-pyran skeleton. Further experiments showed that the nucleophilic component required for the herbicidins, the carbohydrate-based silyl enol ether 2, readily underwent Lewis acid-mediated rearrangement to give levoglucosenone 15.