Amide enolate additions to acylsilanes: in situ generation of unusual and stereoselective homoenolate equivalents.
The synthesis of beta-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 beta-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 gamma-amino-beta-hydroxy amide products derived from the addition of these homoenolates to N-diphenylphosphinyl imines are generated with excellent diastereoselectivity (> or = 20:1) and can be efficiently converted to highly valuable gamma-lactams. Finally, the use of optically active amide enolates delivers beta-hydroxy amide products with high levels of diastereoselectivity (> or = 10:1).
Lettan
Robert B
RB
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.
Galliford
Chris V
CV
Woodward
Chase C
CC
Scheidt
Karl A
KA