Base-Promoted One-Pot Four-Component Domino Strategy Involving Aldehydes and Ketones to Access Multifunctionalized Dihydropyridinones

The synthesis of multifunctionalized dihydropyridinones from aldehydes and ketones involves at least a three-step process, making route shortening a challenging task, especially in achieving a one-pot four-component synthesis via aldehydes and ketones precondensation. Herein, we discovered a [1 + 2 + 1 + 2] four-component domino cyclization reaction, a novel concept in 4CRs with commercially available ketones and aldehydes, which by initially combining aldehydes and ketones with Meldrum's acid and ammonium acetate (NH₄OAc), respectively, they give dihydropyridones (>110 examples). This transformation features inexpensive additives and readily available starting materials, making it appropriate for rapid access to relevant pharmaceutical molecules containing dihydropyridinone-derived heterocycles. Also these compounds can be conveniently converted into trisubstituted and tetrasubstituted pyridines.