Selective Functionalization Of Benzo-Fusedn-Heterocycles By Using In Situ Trapping Metalations

We have prepared some benzo-fusedN-heterocycles derivatives by regioselective metalation of quinoline, isoquinoline, quinoxaline, and quinazoline with LiTMP in the presence of zinc chloride. Applying this strategy to synthesize an analog of the antitumor verubulin illustrates its relevance for medicinal chemistry. Computational calculations of the pK(a)values of the aromatic hydrogens have helped us to rationalize substrate reactivity and metalation regioselectivity by the complex-induced proximity effect concept.