Synthesis of tertiary beta-hydroxy amides by enolate additions to acylsilanes.
The synthesis of tertiary beta-hydroxy amides from acylsilanes, acetamides, and electrophiles is described. 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 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 beta-carbanion onto the carbonyl carbon. The use of optically active amide enolates delivers beta-hydroxy amide products with good levels of diastereoselectivity (>/=10:1).
Lettan
Robert B
RB
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.
Reynolds
Troy E
TE
Galliford
Chris V
CV
Scheidt
Karl A
KA
D000215:Acylation; D000447:Aldehydes / Q000737:chemistry*; D000577:Amides / Q000138:chemical synthesis*; D006900:Hydroxylation; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D012821:Silanes / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D000577:Amides; D007659:Ketones; D012821:Silanes