Access to variously substituted 5,6,7,8-tetrahydro-3H-quinazolin-4-ones via Diels-Alder adducts of phenyl vinyl sulfone to cyclobutene-annelated pyrimidinones

Under basic conditions (Et3N, dioxane), the aromatic amidines 4 and also S-methylisothiourea 4g cleanly undergo Michael addition to methyl 2-chloro-2-cyclopropylideneacelate (5), followed by intramolecular nucleophilic substitution, cyclopropyl to cyclobutyl ring enlargement, deprotonation and cyclization with elimination of methanol to afford the cyclobutene-annelated pyrimidinones 6 in 43-83 % yield (7 examples). Thermal cyclobutene-ring opening of the latter at 175 degrees C followed by regioselective Diels-Alder cycloaddition with phenyl vinyl sulfone gives the 2-aryl-6-(phenylsulfonyl)-5,6,7,8-tetrahydroquinazolinone derivatives 12 in 3983 % yield (7 examples). Base-induced elimination of benzenesulfinic acid and subsequent catalytic hydrogenation leads to the 2-aryltetrahydroquinazolinone derivatives 14 in excellent yields (6 examples). Deprotonation at the sulfonyl-substituted center, alkylation and subsequent elimination of benzenesulfinic acid followed by catalytic hydrogenation gives the 2,6-disubstituted tetrahydroquinazolinones 17a-R. Nucleophilic substitution of the methylthio group in 12g by secondary amines yields the 2-(dialkylamino)tetrahydroquinazolinones 14i-k. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)