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Metallophosphite-Catalyzed Asymmetric Acylation of α,β-Unsaturated Amides

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posted on 01.03.2006, 00:00 by Mary R. Nahm, Justin R. Potnick, Peter S. White, Jeffrey S. Johnson
The l-menthone-derived TADDOL phosphite 6b catalyzes highly enantioselective conjugate additions of acyl silanes to α,β-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 α-silyl-γ-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 γ-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.

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