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

The synthesis of tertiary β-hydroxy amides from acylsilanes, acetamides, and electrophiles is described. The addition of amide enolates to acylsilanes generates β-silyloxy homoenolate reactivity by undergoing a 1,2-Brook rearrangement. These unique nucleophiles formed in situ can then undergo smooth addition to alkyl halides, aldehydes, and ketones. Enolates derived from amides are crucial for the success of this process since ketone enolates suffer from internal return of the β-carbanion onto the carbonyl carbon. The use of optically active amide enolates delivers β-hydroxy amide products with good levels of diastereoselectivity (≥10:1).