Metallophosphite-catalyzed asymmetric acylation of alpha,beta-unsaturated amides.
The l-menthone-derived TADDOL phosphite 6b catalyzes highly enantioselective conjugate additions of acyl silanes to alpha,beta-unsaturated amides. p-Methoxybenzoyl cyclohexyldimethylsilane adds to a variety of N,N-dimethyl acrylamide derivatives in the presence of the lithium salt of 6b. In many instances the alpha-silyl-gamma-ketoamide product undergoes facile enantioenrichment (to 97-99% ee) upon recrystallization. Desilylation with HF.pyr affords the formal Stetter addition products. Baeyer-Villiger oxidation of the desilylated gamma-ketoamides affords useful ester products. An X-ray diffraction study of 6b reveals that the isopropyl group of the menthone ketal influences the position of the syn-pseudoaxial phenyl group in the TADDOL structure. Through a crossover experiment, the silicon migration step in the reaction mechanism is shown to be strictly intramolecular.
Department of Chemistry, University of North Carolina at Chapel Hill, 27599-3290, USA.
Mary R
MR
Nahm
Justin R
JR
Potnick
Peter S
PS
White
Jeffrey S
JS
Johnson
D000215:Acylation; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004148:Dioxolanes / Q000737:chemistry; D008610:Menthol / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D017905:Phosphites / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry*; D013237:Stereoisomerism; D014961:X-Ray Diffraction
D000577:Amides; D004148:Dioxolanes; D017905:Phosphites; D012821:Silanes; D008610:Menthol; C019466:menthone