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.