Asymmetric synthesis and synthetic utility of 2,3- di hydro-4-pyridones

Abstract: Nucleophilic addition of organometallics to chiral 1-acylpyridinium salts occurs with high diastereoselectivity to give N-acyl-2,3-dihydro-4-pyridones, which are useful building blocks for the asymmemc synthesis of various alkaloids. The synthetic utility of these heterocycles lies in the ease of preparation and substitution. Our recent efforts at exploring the scope of this chemistry and its application towards the enantioselective synthesis of various alkaloids are described. Dihydropyridones of the type 1 are interesting heterocycles and attractive building blocks for alkaloid synthesis (Fig. 1). The enone moiety within 1 can be utilized as a Michael acceptor (l) , or 1,Zaddition to the enone carbonyl can be effected by choosing the proper conditions (2). The C-5 position of the heterocycle is susceptible to electrophilic substitution (3a), and alkylation at C-3 can be carried out via the enolate (3b). Due to A(’’3) strain, the C-2 substituent of 1 is forced axial, providing a conformational bias in the molecule (4). This conformational bias can be used to control the stereochemical outcome of 1,2-and 1,Cadditions to the enone as well as alkylations at C-3. In addition to these synthetically useful properties, N-acyldihydropyridones 1 are readily prepared in one step by the addition of organometallics to 1-acyl salts of 4-methoxypyridine (la). We have reported that dihydropyridones 1 are useful intermediates for the stereoselective preparation of several racemic alkaloids (5). Recently, we enhance