A novel and efficient stereo-controlled synthesis of hexahydroquinolinones via the diene-transmissive hetero-Diels-Alder reaction of cross-conjugated azatrienes with ketenes and electrophilic dienophiles

The diene-transmissive hetero-Diels-Alder (DTHDA) reactions of cross-conjugated azatrienes (divinylimines or penta-1,4-dien-3-imines) having an N-aryl, N-alkyl, or N-dimethylamino substituent have been examined. The initial reaction of the azatrienes with diphenylketene at room temperature yielded β-lactams of 2+2] cycloadducts, which upon heating underwent 1,3]-sigmatropic rearrangement to produce the formal 4+2] cycloadducts. The reaction of N-phenylazatriene with dimethylketene or dichloroketene produced the 2+2] cycloadducts only, while the reaction of N-(dimethylamino)azatriene with dichloroketene gave the 4+2] cycloadduct without heating. When the 2+2] cycloadduct has two different vinyl substituents at C-4 of the β-lactam ring, the regioselectivity of the rearrangement depends on steric factors and the electronic demand of the substituents. The second Diels-Alder reaction of the initial 4+2] cycloadducts with electron-deficient dienophiles (TCNE, N-phenylmaleimide) stereoselectively yielded hexahydroquinolinone derivatives. Similarly, a tandem intermolecular-intramolecular mode of the aza-DTHDA reactions produced tetracyclic nitrogen-containing heterocycles in a regio- and stereoselective manner.