Amide Enolate Additions to Acylsilanes: In Situ Generation of Unusual and Stereoselective Homoenolate Equivalents

The synthesis of β-hydroxy carbonyl compounds is an important goal due to their prevalence in bioactive molecules. A novel approach to construct these structural motifs involves the multicomponent reaction of acylsilanes, amides, and electrophiles. 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 addition to alkyl halides, aldehydes, ketones, and imines. The γ-amino-β-hydroxy amide products derived from the addition of these homoenolates to N-diphenylphosphinyl imines are generated with excellent diastereoselectivity (≥20:1) and can be efficiently converted to highly valuable γ-lactams. Finally, the use of optically active amide enolates delivers β-hydroxy amide products with high levels of diastereoselectivity (≥10:1).