Three-Component (Domino) Reaction Affording Substituted Pyrroloquinazolines: Cyclization Regioselectivity and Stereoselectivity

The cyclization involving 2-(aminomethyl)aniline, methyl 3,3,3-trifluoropyruvate, and various oxo compound afforded linearly annulated pyrroloquinazolines, for example, (2R*,3aS*)-2-hydroxy-3a-phenyl-2-trifluoromethyl-3,3a, 4,9-tetrahydropyrrolo[2,1-b]quinazolin-1(2H)-one (cis-8), as the major product, possessing the skeleton of the alkaloids of the vasicine group, along with angularly annulated products, for example, (2S*,3aR*)-2-hydroxy-3a-phenyl-2-trifluorometh-yl-3,3a,4,5-tetrahydropyrrolo[1,2-a]quinazolin-1(2H)-one (cis-18). The effects of the nature of the oxo compound and the temperature on the ratio of the linear and angular cyclization products, as well as the diastereoselectivity of the product formation, were studied, with an increase in temperature leading to improved selectivity. Some of the linear pyrroloquinazolines were stereoselectively didehydrogenated at the quinazoline ring by the trifluoropyruvate.