Copper-Catalyzed Ullmann-Type Coupling Route to Quinazolines

Significance

An efficient copper-catalyzed ­synthesis of quinazolines from amides and (2-bromoaryl)methylamines under copper-­catalyzed conditions is described. The synthesis mimics that of D. Ma et al., who used almost exactly the same conditions (different temperature) earlier for the ­reaction of (2-haloaryl)methyl amines with malonic esters to give isoquinolines (D. Ma and co-workers Org. Lett. 2008, 10, 2761). Yields are moderate to good and the substrate scope was well studied in terms of the amide. However, the scope was poorly investigated with respect to the benzylamine starting materials in spite of the statement that these are readily available. In point of fact, only three simple cases were tested, which are essentially the only readily commercially available substrates. Unfortunately, there is no mention on the reactivity of the corresponding chloro derivatives, many of which are readily available. Mechanism of the reaction is speculated, but no evidence is offered.