Divergent Synthesis of 5,6- and 3,6-Dihydropyridin-2(1H)-one via Intramolecular Knoevenagel Condensation

A simple and friendly strategy for the regioselective synthesis of 5,6and 3,6-dihydropyridin-2(1H)-one via intramolecular Knoevenagel condensation from a common methyl 3-((2-(1,3-dioxolan-2-yl)ethyl)alkylamino)-3-oxopropanoate under acidic conditions is reported.Dihydropyridin-2(1H)-ones derivatives have attracted great attention due to these structural features are found in a wide variety of naturally occurring alkaloids. 1These unsaturated lactams are obtained with the double bond in a specified position, providing great opportunities to functionalized ring, therefore are valuable intermediates for the synthesis of piperidine, 2 quinolone and isoquinoline derivatives 3 and indolizidine and quinolizidine alkaloids. 4 Specifically, 5,6-and 3,6-dihydropyridin-2(1H)-ones are commonly prepared via a ring-closing metathesis reaction. 5Alternative strategies for the specific synthesis of 5,6-dihydropyridin-2(1H)-ones are based on a selenylation/oxidative elimination sequence of the corresponding tetrahydropyridin-2(1H)-one, 6 while 3,6-dihydropyridin-2(1H)-one has been prepared via Palladium catalyzed decarboxylative carbonylation of 5-vinyloxazolidinones, 7 and also through the gold(I)-catalyzed regioselective cyclization of silyl ketene amides or carbamates with alkynes to construct dehydro--lactams. 8 On the other way, Knoevenagel condensation reaction is one of the most important tools for the synthesis of , -unsaturated dicarbonyl compounds as a result of a condensation reaction of aldehydes or ketones with active methylene compounds.The resulting , -unsaturated dicarbonyl or related functional groups can participate in a range of subsequent transformations with preexisting functional groups. 96