Enantioselective metallophosphite-catalyzed nucleophilic acylation of alpha,beta-unsaturated amides and nitrones

I. Metallophosphite-induced nucleophilic acylation of alpha,beta-unsaturated amides: Facilitated catalysis by a diastereoselective retro-[1,4]-Brook rearrangement. Metallophosphite-catalyzed intermolecular alkene acylation reactions between acyl silanes and alpha,beta-unsaturated amides have been developed. These reactions yield alpha-silyl-gamma-ketoamides with high diastereoselectivity; desilylation affords the corresponding gamma-ketoamides. The alpha-silyl amide products can be derivatized to give either the (Z)- or (E)-alpha,beta-unsaturated ketoamides, via the corresponding alpha-bromo-gamma-ketoamide, which is also an isolable product.*; II. 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.*; III. Enantioselective metallophosphite-catalyzed acylation of nitrones to yield N-silyloxy-alpha-amino ketones. Metallophosphites can efficiently catalyze the asymmetric acylation of nitrones to furnish N-silyloxy-alpha-amino ketones in high yields and excellent enantioselectivities. Further applications of these aza-benzoin condensation products involve the reduction of the N-silyloxy-alpha-amino ketones to secondary alpha-amino ketones.*; *Please refer to dissertation for diagrams.