Pd( ii )-Catalyzed [4 + 1 + 1] cycloaddition of simple o -aminobenzoic acids, CO and amines: direct and versatile synthesis of diverse N -substituted quinazoline-2,4(1 H ,3 H )-diones

The mild, efficient, and straightforward synthesis of pharmaceutically and biologically active N 3-substituted and N 1, N 3-disubstituted quinazoline-2,4-(1 H ,3 H )-diones from simple and readily available substrates has been a huge challenge. Described here is a Pd( ii )-catalyzed [4 + 1 + 1] modular synthesis of diverse quinazoline-2,4-(1 H ,3 H )-diones through one-pot cascade reactions of cyclocondensation of o -(alkyl)aminobenzoic acids with CO, amidation of the intermediate isatoic anhydrides with amines, and unprecedented carbonylation of the resulting o -aminobenzamides with CO under 1 atm and 60 °C conditions. The chemoselective and versatile multicomponent reaction allows for the diversities of the products including N 3-substituted and N 1, N 3-disubstituted products, and even makes the substituents on N 1, N 3 the same or different from each other, which cannot be achieved by most traditional synthetic strategies.