Synthesis of Tertiary β-Hydroxy Amides by Enolate Additions to Acyisilanes

摘要

We have developed a strategy for the synthesis of tertiary β-hydroxy amides using β-silyloxy homoenolates accessed from amide enolates and acylsilanes. These unconventional nu-cleophilic species undergo addition to alkyl halides, aldehydes and ketones. Importantly, amide enolates strongly favor C-alkylation of the homoenolate over O-alkylation or the formation of alkoxy cyclopropanes. The use of chiral acetamides affords high levels of diastereoselection for the tertiary alcohol products. Investigations of this Umpolung strategy integrating enolates and the unique reactivity of acylsilanes are ongoing and will be reported in due course.